Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

PubMed

Chien, Jien-Wen; Wang, Lien-Yen; Cheng, Yu-Shan; Tsai, Yi-Giien; Liu, Chin-San

2014-06-01

There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Accuracy of early DMSA scan for VUR in young children with febrile UTI.

PubMed

Zhang, Xin; Xu, Hong; Zhou, Lijun; Cao, Qi; Shen, Qian; Sun, Li; Fang, Xiaoyan; Guo, Wei; Zhai, Yihui; Rao, Jia; Pa, Mier; Zhao, Ruifang; Bi, Yunli

2014-01-01

To evaluate the accuracy of an acute (99m)Tc-dimercaptosuccinic acid (DMSA) scan in predicting dilating vesicoureteral reflux (VUR) among young children with a febrile urinary tract infection (UTI). The medical records of children (≤ 2 years of age), presenting with febrile UTI between January 2000 and December 2011, were retrospectively reviewed. A total of 523 children were included in this study, of whom 397 children (75.9%) had abnormal DMSA results and 178 children (34.0%) were identified as VUR on micturating cystourethrography (MCU). Among all the patients, the number of children with dilating VUR was 151 (28.9%). The rate of abnormal results on DMSA for the dilating VUR group was significantly higher than the rates for the non-VUR and low-grade VUR groups (P < .01). In the <6 months age group and ≥ 6 months age group, the sensitivities of DMSA in predicting dilating VUR were 96.15% and 100.0%, respectively, the negative predictive values were 97.26% and 100.0%, respectively, and the negative likelihood ratios were 0.0911 and 0.0000, respectively. For children ≤ 2 years of age with a febrile UTI, an acute DMSA scan is valuable in the exclusion of dilating VUR. The likelihood of the presence of dilating VUR on MCU is rather low when the result of DMSA is negative. DMSA should be conducted to assess the need for an MCU.

Vitamin E as adjuvant treatment for urinary tract infection in girls with acute pyelonephritis.

PubMed

Yousefichaijan, Parsa; Kahbazi, Manigeh; Rasti, Sara; Rafeie, Mohammad; Sharafkhah, Mojtaba

2015-03-01

Vitamin E is a fat-soluble vitamin that functions as an antioxidant. The aim of this study was to investigate the effects of vitamins E supplementation in combination with antibiotics for the treatment of girls with acute pyelonephritis. This double-blinded randomized controlled trial was conducted on 152 girls aged 5 to 12 years with a first acute pyelonephritis episode based on technetium Tc 99m dimercaptosuccinic acid (99mTc-DMSA). They were randomized to receive a 14-day treatment with only antibiotics (control group; n = 76) and 14-day treatment with supplements of vitamin E (intervention group; n = 76) in addition to the antibiotics. Patients' clinical symptoms were monitored for 14 days and urine culture was performed 3 to 4 days and 7 to 10 days after the start of the treatment and its completion, respectively. All of the girls once underwent DMSA scan 4 to 6 months after the treatment. During the follow-up days, the mean frequency of fever (P = .01), urinary frequency (P = .001), urgency (P = .003), dribbling (P = .001), and urinary incontinence (P = .006) were significantly lower in the intervention group compared to the control group. There was no significant difference in the results of urine culture 3 to 4 days after the start of treatment (P = .16) and 7 to 10 days after its termination (P = .37). There was also no significant difference between the results of DMSA scan 4 to 6 months after the start of treatment (P = .31). Vitamin E supplementation has a significant effect in ameliorating sign and symptoms of UTI. However, further studies are recommended to confirm these findings.

Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: comparative study with voiding cystourethrography.

PubMed

Lee, Sang Kwon; Chang, Yongmin; Park, Noh Hyuck; Kim, Young Hwan; Woo, Seongku

2005-04-01

To evaluate the feasibility of magnetic resonance voiding cystography (MRVC) compared with voiding cystourethrography (VCUG) for detecting and grading vesicoureteral reflux (VUR). MRVC was performed upon 20 children referred for investigation of reflux. Either coronal T1-weighted spin-echo (SE) or gradient-echo (GE) (fast multiplanar spoiled gradient-echo (FMPSPGR) or turbo fast low-angle-shot (FLASH)) images were obtained before and after transurethral administration of gadolinium solution, and immediately after voiding. The findings of MRVC were compared with those of VCUG and technetium-99m ((99m)Tc) dimercaptosuccinic acid (DMSA) single-photon emission computed tomography (SPECT) performed within 6 months of MRVC. VUR was detected in 23 ureterorenal units (16 VURs by both methods, 5 VURs by VCUG, and 2 VURs by MRVC). With VCUG as the standard of reference, the sensitivity of MRVC was 76.2%; the specificity, 90.0%; the positive predictive value, 88.9%; and the negative predictive value, 78.3%. There was concordance between two methods regarding the grade of reflux in all 16 ureterorenal units with VUR detected by both methods. Of 40 kidneys, MRVC detected findings of renal damage or reflux nephropathy in 13 kidneys, and (99m)Tc DMSA renal SPECT detected findings of reflux nephropathy in 17 kidneys. Although MRVC is shown to have less sensitivity for VUR than VCUG, MRVC may represent a method of choice offering a safer nonradiation test that can additionally evaluate the kidneys for changes related to reflux nephropathy. Copyright 2005 Wiley-Liss, Inc.

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals.

PubMed

Mejia, Jorge; Miranda, Ana Claudia Camargo; Durante, Ana Claudia Ranucci; Oliveira, Larissa Rolim de; Barboza, Marycel Rosa Felisa Figols de; Rosell, Katerin Taboada; Jardim, Daniele Pereira; Campos, Alexandre Holthausen; Reis, Marilia Alves Dos; Catanoso, Marcela Forli; Galvis-Alonso, Orfa Yineth; Cabral, Francisco Romero

2016-01-01

To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others. Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

[Should morphology of the upper pole in renal duplication with preserved function and associated ureterocele be taken into account during treatment planning?].

PubMed

Materny, Jacek; Chojnacka, Hanna; Urasińska, Elzbieta; Gawrych, Elzbieta

2011-01-01

The aim of this study was to assess structural changes of the upper pole in renal duplication with coexisting ureterocele with regard to primary and/or secondary lesions. These changes might be of importance in treatment planning. The material of this study consisted of clinical documentation and results of histopathology of 23 upper poles removed due to renal duplication with coexisting ureterocele. The qualification criterion was preserved function of the upper pole seen with 99mTc-DTPA (99mTechnetium diethylenetriaminepentaacetic acid)/99mTc-DMSA (99mTechnetium dimercaptosuccinic acid). Resection of the upper pole was indicated in patients with recurrent urinary tract infections and/or persistent vesicoureteral reflux to the lower pole following endoscopic surgery of the ureterocele and/or low function of the upper pole. Morphological lesions were classified as primary (dysplasia) or secondary lesions. The patients were operated at the Department of Pediatric and Oncologic Surgery, PMU, in 1990-2008. The study group consisted of 17 girls and 6 boys aged from 4 months to 9 years (mean 40 months). Recurrent urinary tract infections noted in 16 (70%) children were the most frequent indication for surgery. The preoperative mean function of the renal poles assessed with DTPA/DMSA represented 6% of the differential renal function. Dysplasia was identified in eight resected renal poles (34%) with coexisting secondary lesions in three of them. Secondary lesions only were seen in 15 poles (66%). There was no correlation between age and incidence of dysplasia during follow-up (Pearson's correlation coefficient r = 0.031). Secondary lesions are a quite frequent finding in resected upper poles. As 66% of the renal poles studied with histopathology revealed secondary lesions only, we believe that renal sparing treatment is justified in cases of urinary duplication with coexisting ureterocele.

The adsorption of 99Tcm dimercaptosuccinic acid onto injection vials.

PubMed

Millar, A M

1984-04-01

It is common practice to dispense radiopharmaceuticals into empty sterile vials for dispatch to the departments where they are to be administered. It has been noted that on withdrawal of technetium-99m dimercaptosuccinic acid injections (99Tcm-DMSA) which have been dispensed into such vials, the activities obtained are lower than expected. To explain this phenomenon, the adsorption of 99Tcm-DMSA onto commercially available, empty, sterile vials has been investigated. The 99Tcm-DMSA solutions were prepared using kits from two manufacturers and were tested in vials from two manufacturers and the original kit vials. Adsorption of 99Tcm in one DMSA/vial combination after storage for 4 h was 49.6% (+/- 4.5% S.E.M.), but typically, adsorption was approximately 12% after 4 h. Although rate of adsorption was found to vary with storage conditions, no conditions satisfactorily overcame the effect. In vials from one manufacturer, the 99Tcm adsorption was predominantly on the glass, while in vials from the other, it was predominantly on the rubber stopper. It is concluded that the compatibility between vials and radiopharmaceuticals must be investigated in the hospital radiopharmacy.

Plain radiography, renography, and 99mTc-DMSA renal scintigraphy before and after extracorporeal shock wave lithotripsy for urolithiasis.

PubMed

Munck, O; Gerquari, I; Møller, J T; Jensen, L I; Thomsen, H S

1992-11-01

Eighteen patients were evaluated before and 5 weeks after the first treatment with extracorporeal shock wave lithotripsy (ESWL) using abdominal plain radiography, 131I-hippuran probe renography, and 99mTc-dimercaptosuccinic acid scintigraphy. In 6 patients no urolithiasis was present on the post ESWL plain radiograph, in 7 the size had decreased, and in 5 the stone mass was unchanged. The renograms were within normal range in the 6 patients who were cured by ESWL, whereas this was the case for only 4 of the 12 who still had renal calculi. In 2 patients pelvic stones had descended into the ureter after ESWL, and the renograms indicated obstruction. Another 3 patients had ureteral stones, whereas in the remaining 7 patients only pelvic stones were found on the plain radiographs. In no patient did the scintigrams reveal scars. It is concluded that abdominal plain radiography of the urinary tract and probe renography are complementary and sufficient in the monitoring of patients with urolithiasis post ESWL.

Three new renal simulators for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Dullius, Marcos; Fonseca, Mateus; Botelho, Marcelo; Cunha, Clêdison; Souza, Divanízia

2014-03-01

Renal scintigraphy is useful to provide both functional and anatomic information of renal flow of cortical functions and evaluation of pathological collecting system. The objective of this study was develop and evaluate the performance of three renal phantoms: Two anthropomorphic static and another dynamic. The static images of the anthropomorphic phantoms were used for comparison with static renal scintigraphy with 99mTc-DMSA in different concentrations. These static phantoms were manufactured in two ways: one was made of acrylic using as mold a human kidney preserved in formaldehyde and the second was built with ABS (acrylonitrile butadiene styrene) in a 3D printer. The dynamic renal phantom was constructed of acrylic to simulate renal dynamics in scintigraphy with 99mTc-DTPA. These phantoms were scanned with static and dynamic protocols and compared with clinical data. Using these phantoms it is possible to acquire similar renal images as in the clinical scintigraphy. Therefore, these new renal phantoms can be very effective for use in the quality control of renal scintigraphy, and image processing systems.

Usefulness of analytical parameters in the management of paediatric patients with suspicion of acute pyelonephritis. Is procalcitonin reliable?

PubMed

Bañuelos-Andrío, L; Espino-Hernández, M; Ruperez-Lucas, M; Villar-Del Campo, M C; Romero-Carrasco, C I; Rodríguez-Caravaca, G

To investigate the usefulness of procalcitonin (PCT) and other analytical parameters (white blood cell count [WBC], C-reactive protein [CRP]) as markers of acute renal damage in children after a first febrile or afebrile urinary tract infection (UTI). A retrospective study was conducted on children with a first episode of UTI admitted between January 2009 to December 2011, and in whom serum PCT, CRP and white blood cell count were measured, as well as assessing the acute renal damage with renal scintigraphy with 99m Tc-DMSA (DMSA) within the first 72h after referral. A descriptive study was performed and ROC curves were plotted, with optimal cut-off points calculated for each parameter. The 101 enrolled patients were divided into two groups according to DMSA scintigraphy results, with 64 patients being classified with acute pyelonephritis (APN), and 37 with UTI. The mean WBC, CRP and PCT values were significantly higher in patients with APN with respect to normal acute DMSA. The area under the ROC curve was 0.862 for PCR, 0.774 for WBC, and 0.731 for PCT. The optimum statistical cut-off value for PCT was 0.285ng/ml (sensitivity 71.4% and specificity 75%). Although the mean levels of fever, WBC, CRP, and PCT were significantly increased in patients with APN than in those who had UTI, the sensitivity and specificity of these analytical parameters are unable to predict the existence of acute renal damage, making the contribution by renal DMSA scintigraphy essential. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

High incidence of vesicoureteric reflux in asymptomatic siblings of children with known reflux

DOE Office of Scientific and Technical Information (OSTI.GOV)

Treves, S.T.; Van den Abbeele, A.D.; Davis, R.T.

1985-05-01

A significant occurrence of vesicoureteric reflux in siblings of children with reflux has been previously suggested. The purpose of this study was to evaluate the incidence of vesicoureteric reflux in asymptomatic siblings of children with vesicoureteric reflux using radionuclide voiding cystography (RNC). A random group of 52 siblings was studied. Their ages were from 2 mos. to 13 yrs. (mean 4 yrs.). Seventy-one percent were female and 29% male, RNC was performed with the patients supine, and Tc-99m pertechnetate (2mCi/1) was infused into the bladder by catheter. A computerized gamma camera recorded the filling and voiding phase of the studymore » at 1 frame/5 sec. Reflux was detected in 40% of the patients. It was bilateral in 17% and unilateral in 23% of the patients. Reflux was identified to the renal pelves in half of the patients. In two of these patients Tc-99m DMSA scans were obtained which revealed significant renal scarring. This study demonstrates the high incidence of reflux of various degrees in these asymptomatic siblings on high risk of developing significant renal disease. Identification and proper treatment of asymptomatic children with vesicoureteric reflux may help prevent the development of renal damage.« less

Novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

PubMed

Liu, Min; Zheng, Yumin; Avcibasi, Ugur; Liu, Shuang

2016-11-01

In this study, novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] ( 99m Tc-ISboroxime-N 3 : R=IS; 99m Tc-MPboroxime-N 3 : R=MP; 99m Tc-PAboroxime-N 3 : R=PA; 99m Tc-PYboroxime-N 3 : R=PY; and 99m Tc-Uboroxime-N 3 : R=5U) were evaluated as heart imaging agents. Complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN 3 and [ 99m TcCl(CDO)(CDOH) 2 B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention. 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were prepared with high RCP (93-98%) while the RCP of 99m Tc-MPboroxime-N 3 and 99m Tc-PAboroxime-N 3 was 80-85%. The myocardial retention curves of 99m Tc-ISboroxime-N 3 , 99m Tc-PYboroxime-N 3 and 99m Tc-Uboroxime-N 3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99m Tc-ISboroxime-N 3 , 0.7±0.1min for 99m Tc-PYboroxime-N 3 and 0.9±0.4min for 99m Tc-Uboroxime-N 3 . The 2-min heart uptake from biodistribution studies followed the ranking order of 99m Tc-ISboroxime-N 3 (3.60±0.68%ID/g)> 99m Tc-PYboroxime-N 3 (2.35±0.37%ID/g)≫ 99m Tc-Uboroxime-N 3 (1.29±0.06%ID/g). 99m Tc-ISboroxime-N 3 had the highest 2-min heart uptake among 99m Tc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for 99m Tc-ISboroxime-N 3 . Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R]. Among the radiotracers evaluated in SD rats, 99m Tc-ISboroxime-N 3 has the highest initial heart uptake with the heart retention comparable to that of 99m Tc-Teboroxime. 99m Tc-ISboroxime-N 3 is a promising alternative to 99m Tc-Teboroxime for SPECT MPI. Copyright © 2016 Elsevier Inc. All rights reserved.

New Gastrin Releasing Peptide Receptor-Directed [99mTc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation.

PubMed

Nock, Berthold A; Charalambidis, David; Sallegger, Werner; Waser, Beatrice; Mansi, Rosalba; Nicolas, Guillaume P; Ketani, Eleni; Nikolopoulou, Anastasia; Fani, Melpomeni; Reubi, Jean-Claude; Maina, Theodosia

2018-04-12

We have previously reported on the gastrin releasing peptide receptor (GRPR) antagonist [ 99m Tc]1, ([ 99m Tc]demobesin 1, 99m Tc-[N 4 '-diglycolate-dPhe 6 ,Leu-NHEt 13 ]BBN(6-13)). [ 99m Tc]1 has shown superior biological profile compared to analogous agonist-based 99m Tc-radioligands. We herein present a small library of [ 99m Tc]1 mimics generated after structural modifications in (a) the linker ([ 99m Tc]2, [ 99m Tc]3, [ 99m Tc]4), (b) the peptide chain ([ 99m Tc]5, [ 99m Tc]6), and (c) the C-terminus ([ 99m Tc]7 or [ 99m Tc]8). The effects of above modifications on the biological properties of analogs were studied in PC-3 cells and tumor-bearing SCID mice. All analogs showed subnanomolar affinity for the human GRPR, while most receptor-affine 4 and 8 behaved as potent GRPR antagonists in a functional internalization assay. In mice bearing PC-3 tumors, [ 99m Tc]1-[ 99m Tc]6 exhibited GRPR-specific tumor uptake, rapidly clearing from normal tissues. [ 99m Tc]4 displayed the highest tumor uptake (28.8 ± 4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3 ± 1.8%ID/g), well surpassing that of [ 99m Tc]1 (5.4 ± 0.7%ID/g at 24 h pi).

Comparison of Tc-99m maraciclatide and Tc-99m sestamibi molecular breast imaging in patients with suspected breast cancer.

PubMed

O'Connor, Michael K; Morrow, Melissa M B; Hunt, Katie N; Boughey, Judy C; Wahner-Roedler, Dietlind L; Conners, Amy Lynn; Rhodes, Deborah J; Hruska, Carrie B

2017-12-01

Molecular breast imaging (MBI) performed with 99m Tc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99m Tc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99m Tc sestamibi and 99m Tc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99m Tc sestamibi and one with 99m Tc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis. Among 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99m Tc sestamibi MBI and 19 of 21 (90%) were seen on 99m Tc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size ( 99m Tc sestamibi, r = 0.84; 99m Tc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99m Tc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99m Tc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99m Tc sestamibi (r s  = 0.12, p = 0.63) or 99m Tc maraciclatide (r s  = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99m Tc sestamibi and 9 of 20 (45%) were seen on 99m Tc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99m Tc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99m Tc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC analysis was 0.83 for 99m Tc sestamibi and 0.87 for 99m Tc maraciclatide (p = 0.64). 99m Tc maraciclatide offered comparable lesion uptake to 99m Tc sestamibi, in both malignant and benign lesions. There was good correlation between lesion extent and uptake measured from both radiopharmaceuticals. 99m Tc maraciclatide offered a marginal (but not significant) improvement in sensitivity over 99m Tc sestamibi. Our findings did not support an association between the uptake of either radiopharmaceutical and tumor molecular subtype. ClinicalTrials.gov, NCT00888589.

Altered [99mTc]Tc-MDP biodistribution from neutron activation sourced 99Mo.

PubMed

Demeter, Sandor; Szweda, Roman; Patterson, Judy; Grigoryan, Marine

2018-01-01

Given potential worldwide shortages of fission sourced 99 Mo/ 99m Tc medical isotopes there is increasing interest in alternate production strategies. A neutron activated 99 Mo source was utilized in a single center phase III open label study comparing 99m Tc, as 99m Tc Methylene Diphosphonate ([ 99m Tc]Tc-MDP), obtained from solvent generator separation of neutron activation produced 99 Mo, versus nuclear reactor produced 99 Mo (e.g., fission sourced) in oncology patients for which an [ 99m Tc]Tc-MDP bone scan would normally have been indicated. Despite the investigational [ 99m Tc]Tc-MDP passing all standard, and above standard of care, quality assurance tests, which would normally be sufficient to allow human administration, there was altered biodistribution which could lead to erroneous clinical interpretation. The cause of the altered biodistribution remains unknown and requires further research.

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

PubMed

Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

2008-07-01

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

PubMed

Vattimo, A; Bertelli, P; Burroni, L

1992-01-01

Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

Ibogaine labeling with 99mTc-tricarbonyl: synthesis and transport at the mouse blood-brain barrier.

PubMed

Tournier, Nicolas; André, Pascal; Blondeel, Sandy; Rizzo-Padoin, Nathalie; du Moulinet d'Hardemarre, Amaury; Declèves, Xavier; Scherrmann, Jean-Michel; Cisternino, Salvatore

2009-12-01

The (99m)Tc-tricarbonyl core may be used as an ideal tool for gamma-labeling ligands in noninvasive SPECT imaging. However, most (99m)Tc-tricarbonyl-labeled agents have difficulty crossing the blood-brain barrier (BBB). We radiolabeled the neuroactive indole ibogaine with (99m)Tc-tricarbonyl and measured its transport into the mouse brain by in situ brain perfusion. We measured the interactions of [(99m)Tc(CO)(3)-ibogaine](+) and (99m)Tc-tricarbonyl with the main BBB efflux transporters P-gp and BCRP in vitro and in vivo. Ibogaine was radiolabeled (yield: over 95%). [(99m)Tc(CO)(3)-ibogaine](+) entered the brain (K(in)) poorly (0.18 microL/g/s), at about the same rate as (99m)Tc-tricarbonyl (0.16 microL/g/s) and [(99m)Tc-sestamibi](+) (0.10 microL/g/s). The CNS tracer [(99m)Tc-HMPAO](0) entered the brain approximately 70-times higher than [(99m)Tc(CO)(3)-ibogaine](+). In vitro studies revealed that neither [(99m)Tc(CO)(3)-ibogaine](+) nor (99m)Tc-tricarbonyl ion were substrates for P-gp or BCRP. But lowering the membrane dipole potential barrier with phloretin enhanced the brain transport of [(99m)Tc(OH(2))(3)(CO)(3)](+) approximately 3-fold. Thus, ibogaine directly labeled with (99m)Tc-tricarbonyl is not suitable for CNS imaging because of its poor uptake. Brain transport is not restricted by efflux transporters but is reduced by its lipophilicity and interaction with the membrane-positive dipole potential. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Comparison of technetium-99m-HMPAO and technetium-99m-ECD cerebral SPECT images in Alzheimer`s disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dyck, C.H. van; Lin, C.H.; Smith, E.O.

1996-11-01

SPECT has shown increasing promise as a diagnostic tool in Alzheimer`s disease (AD). Recently, a new SPECT brain perfusion agent, {sup 99m}Tc-ethyl cysteinate dimer ({sup 99m}Tc-ECD) has emerged with purported advantages in image quality over the established tracer, {sup 99m}Tc-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO). This research aimed to compare cerebral images for ({sup 99m}Tc-HMPAO). This research aimed to compare cerebral images for {sup 99}mTc-HMPAO and {sup 99m}Tc-ECD in discriminating patients with AD form control subjects. 51 refs., 5 figs., 3 tabs.

Towards the Experimental Assessment of the DQE in SPECT Scanners

NASA Astrophysics Data System (ADS)

Fountos, G. P.; Michail, C. M.

2017-11-01

The purpose of this work was to introduce the Detective Quantum Efficiency (DQE) in single photon emission computed tomography (SPECT) systems using a flood source. A Tc-99m-based flood source (Eγ = 140 keV) consisting of a radiopharmaceutical solution of dithiothreitol (DTT, 10-3 M)/Tc-99m(III)-DMSA, 40 mCi/40 ml bound to the grains of an Agfa MammoRay HDR Medical X-ray film) was prepared in laboratory. The source was placed between two PMMA blocks and images were obtained by using the brain tomographic acquisition protocol (DatScan-brain). The Modulation Transfer Function (MTF) was evaluated using the Iterative 2D algorithm. All imaging experiments were performed in a Siemens e-Cam gamma camera. The Normalized Noise Power spectra (NNPS) were obtained from the sagittal views of the source. The higher MTF values were obtained for the Flash Iterative 2D with 24 iterations and 20 subsets. The noise levels of the SPECT reconstructed images, in terms of the NNPS, were found to increase as the number of iterations increase. The behavior of the DQE was influenced by both MTF and NNPS. As the number of iterations was increased, higher MTF values were obtained, however with a parallel, increase of magnitude in image noise, as depicted from the NNPS results. DQE values, which were influenced by both MTF and NNPS, were found higher when the number of iterations results in resolution saturation. The method presented here is novel and easy to implement, requiring materials commonly found in clinical practice and can be useful in the quality control of SPECT scanners.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

PubMed

Vandehey, Nicholas T; O'Neil, James P; Slowey, Aaron J; Boutchko, Rostyslav; Druhan, Jennifer L; Moses, William W; Nico, Peter S

2012-11-20

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

Clinical Trial with Sodium 99mTc-Pertechnetate Produced by a Medium-Energy Cyclotron: Biodistribution and Safety Assessment in Patients with Abnormal Thyroid Function.

PubMed

Selivanova, Svetlana V; Lavallée, Éric; Senta, Helena; Caouette, Lyne; McEwan, Alexander J B; Guérin, Brigitte; Lecomte, Roger; Turcotte, Éric

2017-05-01

A single-site prospective open-label clinical study with cyclotron-produced sodium 99m Tc-pertechnetate ( 99m Tc-NaTcO 4 ) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99m Tc-NaTcO 4 eluted from a generator. Methods: 99m Tc-NaTcO 4 was produced from enriched 100 Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99m Tc-NaTcO 4 , whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99m Tc-NaTcO 4 showed organ and whole-body distributions identical to those of conventional 99m Tc-NaTcO 4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99m Tc-NaTcO 4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99m Tc was equivalent to that with generator-eluted 99m Tc and had no particular features allowing discrimination between the 99m Tc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99m Tc-NaTcO 4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99m Tc-NaTcO 4 in routine clinical practice. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cost and radiation exposure in the workup of febrile pediatric urinary tract infections.

PubMed

Michaud, Jason E; Gupta, Natasha; Baumgartner, Timothy S; Kim, Brian; Bosemani, Thangamadhan; Wang, Ming-Hsien

2016-06-15

Technetium-99m dimercaptosuccinic acid (DMSA) scans are often used in the evaluation of pediatric patients with febrile urinary tract infections (UTIs). Given the prevalence of febrile UTIs, we sought to quantify the cost, radiation exposure, and clinical utility of DMSA scans when compared with dedicated pediatric renal ultrasounds (RUSs). An institutional review board approved retrospective study of children under the age of 18 years evaluated at our institution for febrile UTIs between the years 2004-2013 was conducted. The patients had to meet all of the following inclusion criteria: a diagnosis of vesicoureteral reflux, a fever >38°C, a positive urine culture, and evaluation with a DMSA scan and RUS. A chart review was used to construct a cost analysis of technical and professional fees, radiographic results, and radiation dose equivalents. Overall, 104 children met the inclusion criteria. A total of 122 RUS and 135 DMSA scans were performed. The technical costs of a DMSA scan incurred a 35% cost premium as compared to an RUS. The average effective radiation dose of a single DMSA scan was 2.84 mSv. New radiographic findings were only identified on 7% of those patients who underwent greater than 1 DMSA scan. The utility of the unique information acquired from a DMSA scan as compared to a RUS in the evaluation of febrile UTI must be evaluated on an individual case-by-case basis given the increased direct costs and radiation exposure to the patient. Copyright © 2016 Elsevier Inc. All rights reserved.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

PubMed Central

Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-01

Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

PubMed

Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-24

To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.

Assessment of antioxidative ability in brain: Imaging of glutathione localization with technetium-99M meso-hexamethyl propyleneamine oxime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasaki, T.; Toyama, H.; Oda, K.

1994-05-01

An oxidative stress is postulated to be important in tissue injury after ischemia and reperfusion, inflammation, aging and various disease. Glutathione (GSH), one of the major antioxidants in the brain, is presumed to be responsible for the metabolism and retention of [Tc-99m] HM-PAO. In order to visualize the regional localization of GSH in the brain, the relationship between the concentrations of tissue GSH and uptake of [Tc-99m] meso-HM-PAO and [Tc-99m] d,l-HM-PAO was studied in mice. Increasing load of diethyl maleate (DEM), a reducing agent of GSH and several other thiols, before [Tc-99m] meso-HM-PAO injection, led to a dose dependent decreasemore » of GSH and [Tc-99m] meso-HM-PAO. At the highest dose of loaded DEM, the uptake of [Tc-99m] meso-HM-PAO in the brain was decreased to 20-30% of the control. In contrast, pretreatment with DEM did little affect the [Tc-99m] d,l-HM-PAO uptake. To elucidate the retention mechanism of [Tc-99m] HM-PAO in brain, we studied the in vitro interactions of [Tc-99m] meso-HMPAO and [Tc-99m] d,l-HM-PAO with GSH, ascorbate and cysteine by measuring octanol-extractable radioactivity, which is remaining intact [Tc-99m] HM-PAO, as a function of incubation period. The disappearance raw of [Tc-99m] meso-HMPAO and [TC-99m] d,l-HM-PAO were 0.18 and 0.96%/min, respectively. Either meso or d,l-isomer did not interact with ascorbate or cysteine. This result suggested that the retention mechanism of [Tc-99m] meso- and d,l-isomers in brain was related to their specific interaction with GSH, and did not related to non-specific interaction with various thiols or other reducing agents. This extremely high reaction rate of [Tc-99m] d,l-HM-PAO with GSH could explain the capability of a small amount of GSH to trap [Tc-99m] d,l-HM-PAO in maximum DEM loading. These results indicated that [Tc-99m] meso-HMPAO would be suitable to image the concentration of GSH in the brain, as opposed d,l-isomer that images blood flow.« less

A novel Tc-99m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine hindlimb ischemia model.

PubMed

Hyoun Kim, Myoung; Kim, Seul-Gi; Guhn Kim, Chang; Kim, Dae-Weung

2017-03-01

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of Biological Properties of 99mTc-Labeled Cyclic RGD Peptide Trimer and Dimer Useful as SPECT Radiotracers for Tumor Imaging

PubMed Central

Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

2016-01-01

Introduction This study sought to evaluate a 99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99mTc-3P-RGD2 in the same animal model. Methods HYNIC-4P-RGD3 was prepared by reacting 4P-RGD3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99mTc-4P-RGD3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99mTc-3P-RGD2 (a αvβ3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the αvβ3 specificity of 99mTc-4P-RGD3. Results 99mTc-4P-RGD3 was prepared with >95% RCP and high specific activity (~200 GBq/µmol). 99mTc-4P-RGD3 and 99mTc-3P-RGD2 shared almost identical tumor uptake and similar biodistribution properties. 99mTc-4P-RGD3 had higher uptake than 99mTc-3P-RGD2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99mTc-4P-RGD3 and 99mTc-3P-RGD2. Conclusion Increasing peptide multiplicity from 3P-RGD2 to 4P-RGD3 offers no advantages with respect to the tumor-targeting capability. 99mTc-4P-RGD3 is as good a SPECT radiotracer as 99mTc-3P-RGD2 for imaging αvβ3-positive tumors. PMID:27556955

Experimental study of {sup 99m}Tc-aluminum oxide use for sentinel lymph nodes detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernov, V. I., E-mail: Chernov@oncology.tomsk.ru; Sinilkin, I. G.; Zelchan, R. V.

The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis was researched on 50 white male rats. The possibility of the use of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particlemore » was 52–77 nm for {sup 99m}Tc-Al{sub 2}O{sub 3} and 16.7–24.5 nm for {sup 99m}Tc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of {sup 99}mTc-Al{sub 2}O{sub 3} was 8.6% in it, and the accumulation of {sup 99m}Tc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of {sup 99m}Tc-Al{sub 2}O{sub 3} in the lymph node was significantly higher than {sup 99m}Tc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis actively accumulated into the lymphatic system. By using {sup 99m}Tc-Al{sub 2}O{sub 3} inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of {sup 99m}Tc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of {sup 99m}Tc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulates actively in the lymph nodes several times as compared to the imported analogue and its practical application will facilitate intraoperative identification of sentinel lymph nodes.« less

Evaluation of New Tc-99m-Labeled Arg-X-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Peptides for Melanoma Imaging

PubMed Central

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of two new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg11)CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg11)CCMSH peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg11)CCMSH and RVD-Lys-(Arg11)CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH displayed high melanoma uptake. 99mTc-RTD-Lys-(Arg11)CCMSH exhibited the peak tumor uptake of 18.77 ± 5.13% ID/g at 2 h post-injection, whereas 99mTc-RVD-Lys-(Arg11)CCMSH reached the peak tumor uptake of 19.63 ± 4.68% ID/g at 4 h post-injection. Both 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h post-injection. The renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h post-injection, respectively. The melanoma lesions were clearly visualized by SPECT/CT using either 99mTc-RTD-Lys-(Arg11)CCMSH or 99mTc-RVD-Lys-(Arg11)CCMSH as an imaging probe at 2 h post-injection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH. However, high renal uptake of 99mTc-RTD-Lys-(Arg11)CCMSH and 99mTc-RVD-Lys-(Arg11)CCMSH need to be reduced to facilitate their future applications. PMID:23885640

Evaluation of new Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides for melanoma imaging.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-09-03

The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution and melanoma imaging properties of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The IC50 values of RTD-Lys-(Arg(11))CCMSH and RVD-Lys-(Arg(11))CCMSH were 0.7 ± 0.07 and 1.0 ± 0.3 nM in B16/F1 melanoma cells. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH displayed high melanoma uptake. (99m)Tc-RTD-Lys-(Arg(11))CCMSH exhibited the highest tumor uptake of 18.77 ± 5.13% ID/g at 2 h postinjection, whereas (99m)Tc-RVD-Lys-(Arg(11))CCMSH reached the highest tumor uptake of 19.63 ± 4.68% ID/g at 4 h postinjection. Both (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH showed low accumulation in normal organs (<1.7% ID/g) except for the kidneys at 2 h postinjection. The renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH was 135.14 ± 23.62 and 94.01 ± 18.31% ID/g at 2 h postinjection, respectively. The melanoma lesions were clearly visualized by single-photon emission computed tomography (SPECT)/CT using either (99m)Tc-RTD-Lys-(Arg(11))CCMSH or (99m)Tc-RVD-Lys-(Arg(11))CCMSH as an imaging probe at 2 h postinjection. Overall, the introduction of Thr or Val residue retained high melanoma uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH. However, high renal uptake of (99m)Tc-RTD-Lys-(Arg(11))CCMSH and (99m)Tc-RVD-Lys-(Arg(11))CCMSH need to be reduced to facilitate their future applications.

Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors.

PubMed

Kobayashi, Masato; Matsunari, Ichiro; Nishi, Kodai; Mizutani, Asuka; Miyazaki, Yoshiharu; Ogai, Kazuhiro; Sugama, Jyunko; Shiba, Kazuhiro; Kawai, Keiichi; Kinuya, Seigo

2016-05-01

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors. 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT. The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection. Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

Evaluation of (99)  (m)TcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with (99)  (m)Tc-sestamibi.

PubMed

Bu, Lihong; Li, Renfei; Jin, Zhongnan; Wen, Xiaofei; Liu, Shuang; Yang, Baofeng; Shen, Baozhong; Chen, Xiaoyuan

2011-02-01

(99)  (m)TcN-MPO ([(99)  (m)TcN(mpo)(PNP5)](+): mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic (99)  (m)Tc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi in normal dogs, and to evaluate the potential of (99)  (m)TcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Five normal mongrel dogs were injected intravenously with (99)  (m)TcN-MPO. Venous blood samples were collected via a femoral vein catheter at 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 60, and 90 min post-injection (p.i.). Anterior-posterior planar images were acquired by γ-camera at 10, 20, 30, 60, 90, and 120 min p.i. Regions of interest (ROIs) were drawn around the heart, liver, and lungs. The heart/liver and heart/lung ratios were calculated by dividing the mean counts in heart ROI by the mean counts in the liver and lung ROI, respectively. For comparison, (99)  (m)Tc-sestamibi was also evaluated in the same five dogs. The interval period between the two examinations was 1 week to eliminate possible interference between these two radiotracers. In addition, single positron emission computed tomography (SPECT) images in the canine infarct model were collected 24 h after myocardial infarction at 30 and 60 min after the administration of (99)  (m)TcN-MPO (n = 4) or (99)  (m)Tc-Sestamibi (n = 4). It was found that (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi displayed very similar blood clearance characteristics during the first 90 min p.i. Both (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min and less than 5% at 30 min p.i. (99)  (m)TcN-MPO and (99)  (m)Tc-Sestamibi both showed good heart/lung contrast. The heart/liver ratio of (99)  (m)TcN-MPO increased with time (0.53 ± 0.06 at 10 min, 0.90 ± 0.062 at 30 min, and 1.22 ± 0.06 at 60 min p.i.), whereas the heart/liver ratio of (99)  (m)Tc-Sestamibi remained low at all time points (0.50 ± 0.03 at 10 min, 0.64 ± 0.03 at 30 min, and 0.60 ± 0.02 at 60 min p.i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of (99)  (m)TcN-MPO but not after (99)  (m)Tc-Sestamibi. The combination of reasonable heart uptake with rapid hepatobiliary excretion makes (99)  (m)TcN-MPO a promising new radiotracer for myocardial perfusion imaging.

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

PubMed

Martini, Petra; Boschi, Alessandra; Cicoria, Gianfranco; Zagni, Federico; Corazza, Andrea; Uccelli, Licia; Pasquali, Micòl; Pupillo, Gaia; Marengo, Mario; Loriggiola, Massimo; Skliarova, Hanna; Mou, Liliana; Cisternino, Sara; Carturan, Sara; Melendez-Alafort, Laura; Uzunov, Nikolay M; Bello, Michele; Alvarez, Carlos Rossi; Esposito, Juan; Duatti, Adriano

2018-05-30

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [ 99m Tc][TcO 4 ] - ubiquitously employed for the production of 99m Tc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100 Mo(p,2n) 99m Tc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99 Mo/ 99m Tc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example. Copyright © 2018 Elsevier Ltd. All rights reserved.

Top-down approach is possible strategy for predicting breakthrough fUTIs and renal scars in infants.

PubMed

Kawai, Shina; Kanai, Takahiro; Hyuga, Taiju; Nakamura, Shigeru; Aoyagi, Jun; Ito, Takane; Saito, Takashi; Odaka, Jun; Furukawa, Rieko; Aihara, Toshinori; Nakai, Hideo

2017-07-01

Acute-phase technetium-99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r-fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r-fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r-fUTI. Seventy-nine consecutive infants (male: female, 60:19) with fUTI were enrolled in this study. DMSA scintigraphy was performed in the acute phase, and patients with defect underwent voiding cystourethrography and chronic-phase (6 months later) DMSA scintigraphy. Patients were followed on continuous antibiotic prophylaxis (CAP). Defects on acute-phase DMSA scintigraphy were observed in 32 children (40.5%) of 79. The mean follow-up observation period was 17.0 ± 10.1 months. Four patients had r-fUTI (5%). Two of them had defects on DMSA scintigraphy in both the acute phase and chronic phase, and had bilateral vesicoureteral reflux (VUR) grade IV. Two others had r-fUTI without defects on DMSA and did not have VUR. Twelve patients had defect on chronic-phase DMSA scintigraphy and four of them had no VUR. The top-down approach is a possible method for predicting r-fUTI in infants and does not miss clinically significant VUR. Also, given that the prevalence of r-fUTI was 5% regardless of the presence of defects on acute-phase DMSA, then, in conjunction with genital hygiene and CAP, acute-phase DMSA might be unnecessary if chronic-phase DMSA is performed for all patients to detect renal scar. © 2017 Japan Pediatric Society.

Technetium glucose complexes as potential cancer imaging agents.

PubMed

Dapueto, Rosina; Aguiar, Rodrigo B; Moreno, María; Machado, Camila M L; Marques, Fabio L N; Gambini, Juan P; Chammas, Roger; Cabral, Pablo; Porcal, Williams

2015-10-01

GLUT's (facilitative glucose transporters) over-expression in tumor cells has allowed the detection of several cancer types, using a glucose analogue ((18)F-FDG) with PET images, worldwide. New glucose analogs radiolabeled with (99m)Tc could be a less-expensive and more accessible alternative for diagnosis using SPECT imaging. d-Glucose ((99m)Tc-IDAG) and 2-d-deoxyglucose ((99m)Tc-AADG) organometallic complexes were proposed and studied as potential (18)F-FDG surrogates. The glucose complexes were prepared and evaluated as potential cancer imaging agents, in a melanoma tumor model. Iminodiacetic acid (IDA) and aminoacetate (AA) moieties were chosen as chelating system for radiolabeling with (99m)Tc. Tumor uptake of the formed complexes was evaluated in B16 murine cell line in vitro and in vivo in melanoma bearing C57BL/6 mice. In vitro and in vivo studies were conducted with (18)F-FDG in order to compare the uptake of (99m)Tc-glucose complexes in the tumor model. IDAG and AADG compounds were synthesized and radiolabeled with (99m)TcO4(-) to obtain the (99m)Tc-IDAG and (99m)Tc-AADG complexes in high yield and stability. In vitro cell studies showed maximum uptake at 60 min for complexes, (99m)Tc-IDAG and (99m)Tc-AADG, with 6% and 2%, respectively. Biodistribution studies showed high tumor uptake one hour post-injection, reaching tumor-to-muscle ratios of 12.1 ± 3.73 and 2.88 ± 1.40 for (99m)Tc-IDAG and (99m)Tc-AADG, respectively. SPECT and micro-SPECT-CT images acquired after the injection of (99m)Tc-IDAG showed accumulation in tumor sites, suggesting that this glucose complex would be a promising candidate for cancer imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced (99m)Tc.

PubMed

Tanguay, J; Hou, X; Esquinas, P; Vuckovic, M; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-11-07

Cyclotron production of 99mTc through the (100)Mo(p,2n)99mTc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. Like most radioisotope production methods, cyclotron production of 99mTc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced 99mTc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of 99mTc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify (99)Mo breakthrough in generator-produced 99mTc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of 99mTc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of 99mTc can be used to estimate increases in radiation dose (relative to pure 99mTc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of 93gTc, 93mTc, 94gTc, 94mTc, 95mTc, 95gTc, and 96gTc, in addition to a number of non-Tc impurities.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Esquinas, P.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-11-01

Cyclotron production of {{}99\\text{m}} Tc through the 100Mo(p,2n){{}99\\text{m}} Tc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. Like most radioisotope production methods, cyclotron production of {{}99\\text{m}} Tc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced {{}99\\text{m}} Tc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of {{}99\\text{m}} Tc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify 99Mo breakthrough in generator-produced {{}99\\text{m}} Tc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of {{}99\\text{m}} Tc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of {{}99\\text{m}} Tc can be used to estimate increases in radiation dose (relative to pure {{}99\\text{m}} Tc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of {{}93\\text{g}} Tc, {{}93\\text{m}} Tc, {{}94\\text{g}} Tc, {{}94\\text{m}} Tc, {{}95\\text{m}} Tc, {{}95\\text{g}} Tc, and {{}96\\text{g}} Tc, in addition to a number of non-Tc impurities.

Monoanionic 99mTc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers.

PubMed

Lipowska, Malgorzata; Klenc, Jeffrey; Jarkas, Nashwa; Marzilli, Luigi G; Taylor, Andrew T

2017-04-01

99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of 131 I-OIH but the clearance of 99m Tc(CO) 3 (NTA) and 131 I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic 99m Tc(CO) 3 (NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the 99m Tc(CO) 3 (NTA) metal-coordination sphere but with uncharged pendant groups. 99m Tc(CO) 3 complexes with N-(2-acetamido)iminodiacetic acid (ADA), N-(2-hydroxyethyl)iminodiacetic acid (HDA) and N-(fluoroethyl)iminodiacetic acid (FEDA) were prepared using a tricarbonyl kit and isolated by HPLC. The pharmacokinetics were evaluated in Sprague-Dawley rats, with 131 I-OIH as an internal control; urine was analyzed for metabolites. Plasma protein binding and erythrocyte uptake were determined from the 10min blood samples. Re(CO) 3 (FEDA), the analog of 99m Tc(CO) 3 (FEDA), was prepared and characterized. 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA) were efficiently prepared as a single species with high radiochemical purities (>99%). These new monoanionic 99m Tc(CO) 3 tracers with uncharged dangling groups all showed rapid blood clearance and high specificity for renal excretion. Activity in the urine, as a percent of 131 I-OIH at 10 and 60min, was 96% and 99% for ADA, 96% and 100% for HDA, and 100% and 99% for FEDA, respectively. Each new tracer was excreted unchanged in the urine. The Re(CO) 3 (FEDA) structure adds compelling evidence that such 99m Tc(CO) 3 (NTA) analogs have metal-coordination spheres identical to that of 99m Tc(CO) 3 (NTA). New tracers lacking the negatively charged pendant carboxyl group previously thought to be essential for rapid renal extraction, 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA), exhibit pharmacokinetics in rats comparable to those of 99m Tc(CO) 3 (NTA) and 131 I-OIH. Furthermore, these encouraging results in rats warrant evaluation of this new tracer type in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis, Characterization, and Preclinical Evaluation of (99m)Tc-Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer.

PubMed

Yadav, Neelam; Chuttani, Krishna; Mishra, Anil K; Singh, Bachcha

2016-05-01

The novel tetraaza macrobicyclic chelator 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione (TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos-1(21),17,19-triene-2,7,11,16-tetradione (OPTT) were synthesized, characterized, and radiolabeled with (99m)Tc to produce (99m)Tc-TBPD and (99m)Tc-OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of (99m)Tc-TBPD and (99m)Tc-OPTT was found 98% and 97%. In vitro serum stability of (99m)Tc-TBPD was found to be 95.2%, while that of (99m)Tc-OPTT 94.2% up to 24 h. Blood kinetics experiments of (99m)Tc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of (99m)Tc-TBPD and 99.42 ± 0.88% activity of (9m)Tc-OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of (99m) Tc-TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of (99m)Tc-OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of (99m)Tc-TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of (99m)Tc-OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines. © 2015 John Wiley & Sons A/S.

Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons.

PubMed

Boschi, Alessandra; Martini, Petra; Pasquali, Micol; Uccelli, Licia

2017-09-01

99m Tc is the most commonly used radionuclide in the field of diagnostic imaging, a noninvasive method intended to diagnose a disease, assess the disease state and monitor the effects of treatments. Annually, the use of 99m Tc, covers about 85% of nuclear medicine applications. This isotope releases gamma rays at about the same wavelength as conventional X-ray diagnostic equipment, and owing to its short half-life (t ½  = 6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of 99m Tc and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient's radiation exposure. 99m Tc is usually supplied to hospitals through a 99 Mo/ 99m Tc radionuclide generator system where it is produced from the β decay of the parent nuclide 99 Mo (t ½  = 66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced 99 Mo, has forced the scientific community to investigate alternative production routes for 99m Tc. One solution was to consider cyclotron-based methods as potential replacement of reactor-based technology and the nuclear reaction 100 Mo(p,2n) 99m Tc emerged as the most worthwhile approach. This review reports some achievements about 99m Tc produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of 99m Tc from the irradiated targets, the preparation of high purity 99m Tc radiopharmaceuticals and the first clinical studies carried out with cyclotron produced 99m Tc are described.

Assessment of the direct cyclotron production of (99m)Tc: An approach to crisis management of (99m)Tc shortage.

PubMed

Rovais, Mohammad Reza Aboudzadeh; Aardaneh, Khosro; Aslani, Gholamreza; Rahiminejad, Ali; Yousefi, Kamran; Boulouri, Fatemeh

2016-06-01

Nowadays, the cyclotron production of technetium-99m ((99m)Tc) has been increased, due to the worldwide (99m)Tc generator shortage. In the present work, an improved strategy for the production of (99m)Tc, using the proton irradiation of the enriched (100)Mo was developed. The performance of this method in terms of the production yield, chemical purity, radiochemical purity, as well as radionuclide purity was evaluated. The average production yield was measured to be 356MBqμA(-1)h(-1). A good agreement was found between the calculated production yield and the experimental one. The radiochemical separation and total recovery yields of (99m)Tc were 92% and 69%, respectively. The radiochemical and the radionuclide purities of the (99m)Tc were 99% and >99.99% at the end of purification, respectively. The results of quality control tests (QC) support the concept that cyclotron-produced (99m)Tc is suitable for preparation of USP-compliant. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL.

PubMed

Takahashi, Nobukazu; Yang, David J; Kohanim, Saady; Oh, Chang-Sok; Yu, Dong-Fang; Azhdarinia, Ali; Kurihara, Hiroaki; Zhang, Xiaochun; Chang, Joe Y; Kim, E Edmund

2007-03-01

To evaluate the feasibility of using (99m)Tc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases. 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of (99m)Tc-GAP-EDL were conducted in ER(+) cell lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h. Each rat was administered (99m)Tc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of (99m)Tc-GAP-EDL was via an ER-mediated process. In the tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES) 1 h prior to receiving (99m)Tc-GAP-EDL. In the endometriosis model, part of the rabbit uterine tissue was dissected and grafted to the peritoneal wall. The rabbit was administered with (99m)Tc-GAP-EDL. There was a 10-40% reduction in uptake of (99m)Tc-GAP-EDL in cells treated with DES or tamoxifen compared with untreated cells. Western blot analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution studies showed that tumor uptake and tumor-to-muscle count density ratio in (99m)Tc-GAP-EDL groups were significantly higher than those in (99m)Tc-GAP groups at 4 h. Among (99m)Tc-GAP-EDL groups, region of interest analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Cellular or tumor uptake of (99m)Tc-GAP-EDL occurs via an ER-mediated process. (99m)Tc-GAP-EDL is a useful agent for imaging functional ER(+) disease.

The Role of (99m)Tc-Annexin V Apoptosis Scintigraphy in Visualizing Early Stage Glucocorticoid-Induced Femoral Head Osteonecrosis in the Rabbit.

PubMed

Wang, Xiaolong; Liu, Yu; Wang, Xuemei; Liu, Rui; Li, Jianbo; Zhang, Guoliang; Li, Qiang; Wang, Lei; Bai, Zhigang; Zhao, Jianmin

2016-01-01

To validate the ability of (99m)Tc-Annexin V to visualize early stage of glucocorticoid-induced femoral head necrosis by comparing with (99m)Tc-MDP bone scanning. Femoral head necrosis was induced in adult New Zealand white rabbits by intramuscular injection of methylprednisolone. (99m)Tc-Annexin scintigraphy and (99m)Tc-MDP scans were performed before and 5, 6, and 8 weeks after methylprednisolone administration. Rabbits were sacrificed at various time points and conducted for TUNEL and H&E staining. All methylprednisolone treated animals developed femoral head necrosis; at 8 weeks postinjection, destruction of bone structure was evident in H&E staining, and apoptosis was confirmed by the TUNEL assay. This was matched by (99m)Tc-Annexin V images, which showed a significant increase in signal over baseline. Serial (99m)Tc-Annexin V scans revealed that increased (99m)Tc-Annexin V uptake could be observed in 5 weeks. In contrast, there was no effect on (99m)Tc-MDP signal until 8 weeks. The TUNEL assay revealed that bone cell apoptosis occurred at 5 weeks. (99m)Tc-Annexin V is superior to (99m)Tc-MDP for the early detection of glucocorticoid-induced femoral head necrosis in the rabbit and may be a better strategy for the early detection of glucocorticoid-induced femoral head necrosis in patients.

Prediction of Cortical Defect Using C-Reactive Protein and Urine Sodium to Potassium Ratio in Infants with Febrile Urinary Tract Infection

PubMed Central

Jung, Su Jin

2016-01-01

Purpose We investigated whether C-reactive protein (CRP) levels, urine protein-creatinine ratio (uProt/Cr), and urine electrolytes can be useful for discriminating acute pyelonephritis (APN) from other febrile illnesses or the presence of a cortical defect on 99mTc dimercaptosuccinic acid (DMSA) scanning (true APN) from its absence in infants with febrile urinary tract infection (UTI). Materials and Methods We examined 150 infants experiencing their first febrile UTI and 100 controls with other febrile illnesses consecutively admitted to our hospital from January 2010 to December 2012. Blood (CRP, electrolytes, Cr) and urine tests [uProt/Cr, electrolytes, and sodium-potassium ratio (uNa/K)] were performed upon admission. All infants with UTI underwent DMSA scans during admission. All data were compared between infants with UTI and controls and between infants with or without a cortical defect on DMSA scans. Using multiple logistic regression analysis, the ability of the parameters to predict true APN was analyzed. Results CRP levels and uProt/Cr were significantly higher in infants with true APN than in controls. uNa levels and uNa/K were significantly lower in infants with true APN than in controls. CRP levels and uNa/K were relevant factors for predicting true APN. The method using CRP levels, u-Prot/Cr, u-Na levels, and uNa/K had a sensitivity of 94%, specificity of 65%, positive predictive value of 60%, and negative predictive value of 95% for predicting true APN. Conclusion We conclude that these parameters are useful for discriminating APN from other febrile illnesses or discriminating true APN in infants with febrile UTI. PMID:26632389

The results of different diagnostic imaging studies used in children with urinary tract infection

PubMed Central

Alghamdi, Ahmed Hassan; Ghamdi, Jameel Al; Al-Dammas, Ali

2015-01-01

Urinary tract infections (UTI) can cause significant renal scarring, which can be complicated by hypertension and renal impairment. This study describes the outcome of different imaging modalities in children with UTI and its relation to age, sex and type of UTI. Our objective was to describe the frequencies of different imaging studies, which were used to investigate children with UTI at King Fahad Hospital (KFH) between the years 2003 and 2008. This is a descriptive study of all children presenting with UTI at KFH from 2003 to 2008. The study population, 100 children, were divided into 3 age groups; first group (> 1 month to 2 years); second group (> 2 to 5 years), third group (> 5 to 12 years). All enrolled children were confirmed to have had UTI via urinary cultures. Ninety seven (97%) patients underwent renal ultrasonography (US), 77 (77%) had a 99mTc-dimercaptosuccinic acid (DMSA) scan within 2 months of presentation, and 60 (60%) patients underwent micturating cystourethrogram (MCUG), mainly those with an abnormal DMSA scan. A total of 100 patients screened, 10 (10%) were males and 90 (90%) were females, first age group constituted 10%, second age group was 25%, third age groups was 65%. E-coli was isolated in 84% of patients, 60% had recurrent UTI, 45% had pyelonephritis, 48.4% had abnormal renal US, 61% had an abnormal DMSA scan, and 26.6% had abnormal MCUG. UTI can cause significant morbidity in children if not managed properly. Imaging studies are useful in identifying children who require advanced medical intervention; however, such studies should be performed only when indicated. PMID:27493418

A comparison of rat SPECT images obtained using (99m)Tc derived from 99Mo produced by an electron accelerator with that from a reactor.

PubMed

Galea, R; Wells, R G; Ross, C K; Lockwood, J; Moore, K; Harvey, J T; Isensee, G H

2013-05-07

Recent shortages of molybdenum-99 ((99)Mo) have led to an examination of alternate production methods that could contribute to a more robust supply. An electron accelerator and the photoneutron reaction were used to produce (99)Mo from which technetium-99m ((99m)Tc) is extracted. SPECT images of rat anatomy obtained using the accelerator-produced (99m)Tc with those obtained using (99m)Tc from a commercial generator were compared. Disks of (100)Mo were irradiated with x-rays produced by a 35 MeV electron beam to generate about 1110 MBq (30 mCi) of (99)Mo per disk. After target dissolution, a NorthStar ARSII unit was used to separate the (99m)Tc, which was subsequently used to tag pharmaceuticals suitable for cardiac and bone imaging. SPECT images were acquired for three rats and compared to images for the same three rats obtained using (99m)Tc from a standard reactor (99)Mo generator. The efficiency of (99)Mo-(99m)Tc separation was typically greater than 90%. This study demonstrated the delivery of (99m)Tc from the end of beam to the end user of approximately 30 h. Images obtained using the heart and bone scanning agents using reactor and linac-produced (99m)Tc were comparable. High-power electron accelerators are an attractive option for producing (99)Mo on a national scale.

Development and Pharmacological Evaluation of New Bone-Targeted (99m)Tc-Radiolabeled Bisphosphonates.

PubMed

Makris, George; Tseligka, Eirini D; Pirmettis, Ioannis; Papadopoulos, Minas S; Vizirianakis, Ioannis S; Papagiannopoulou, Dionysia

2016-07-05

A novel bisphosphonate, 1-(3-aminopropylamino)ethane-1,1-diyldiphosphonic acid (3), was coupled to the tridentate chelators di-2-picolylamine, 2-picolylamine-N-acetic acid, iminodiacetic acid, 3-((2-aminoethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid, and 2-((2-carboxyethyl)thio)-3-(1H-imidazol-4-yl)propanoic acid to form ligands 6, 9, 11, 15, and 19, respectively. Organometallic complexes of the general formula [Re/(99m)Tc(CO)3(κ(3)-L)] were synthesized, where L denotes ligand 6, 9, 11, 15, or 19. The rhenium complexes were prepared at the macroscopic level and characterized by spectroscopic methods. The technetium-99m organometallic complexes were synthesized in high yield and were identified by comparative reversed-phase HPLC with their Re analogues. The (99m)Tc tracers were stable in vitro and exhibited binding to hydroxyapatite. In biodistribution studies, all of the (99m)Tc complexes exhibited high bone uptake superior to that of 25, which is the directly (99m)Tc-labeled bisphosphonate 3, and comparable to that of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP). The tracers [(99m)Tc(CO)3(6)] (26), [(99m)Tc(CO)3(9)] (27), [(99m)Tc(CO)3(11)] (28), and [(99m)Tc(CO)3(15)] (29) exhibited higher bone/blood ratios than (99m)Tc-MDP. 26 had the highest bone uptake at 1 h p.i. The new bisphosphonates showed no substantial growth inhibitory capacity in PC-3, Saos-2, and MCF-7 established cancer cell lines at low concentrations. Incubation of 26 with the same cancer cell lines indicated a rapid and saturated uptake. The promising properties of 26-29 indicate their potential for use as bone-imaging agents.

(99m)Tc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice.

PubMed

Kaloudi, Aikaterini; Nock, Berthold A; Lymperis, Emmanouil; Krenning, Eric P; de Jong, Marion; Maina, Theodosia

2016-06-01

In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE-inhibition on the pharmacokinetic profile of three (99m)Tc-labeled gastrins of varying peptide chain length: [(99m)Tc]SG6 ([(99m)Tc-N4-Gln(1)]gastrin(1-17)), [(99m)Tc]DG2 ([(99m)Tc-N4-Gly(4),DGlu(5)]gastrin(4-17)) and [(99m)Tc]DG4 ([(99m)Tc-N4-DGlu(10)]gastrin(10-17)). Mouse blood samples were collected 5min after injection of each of [(99m)Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431-CCK2R(+/-) xenografts at 4h postinjection (pi). [(99m)Tc]SG6 or [(99m)Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [(99m)Tc]DG2 control and PA animal groups were only included. Treatment of mice with PA induced significant stabilization of (99m)Tc-radiotracers in peripheral blood, while treatment with Lis or Lis+PA affected the stability of des(Glu)5 [(99m)Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (P<0.01). Only [(99m)Tc]DG4 profited by single Lis (2.06±0.39%ID/g vs 0.99±0.13%ID/g in controls) or combined Lis+PA coinjection (8.91±1.61%ID/g vs 4.89±1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [(99m)Tc]DG4 (<1.9%ID/g) resulting in the most optimal tumor-to-kidney ratios. In situ NEP/ACE-inhibition diversely affected the in vivo profile of (99m)Tc-radioligands based on different-length gastrins. Truncated [(99m)Tc]DG4 exhibited overall the most attractive profile during combined NEP/ACE-inhibition in mouse models, providing new opportunities for CCK2R-expressing tumor imaging in man with SPECT. Copyright © 2016 Elsevier Inc. All rights reserved.

99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI

PubMed Central

Gao, Shi; Ji, Tiefeng; Wen, Qiang; Song, Yan; Zhu, Lei; Xu, Zheli; Liu, Lin

2014-01-01

Purpose To compare the potential application of 99mTc-3P-Arg-Gly-Asp (99mTc-3P4-RGD2) scintimammography (SMM) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions. Method Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. 99mTc-3P4-RGD2 and 99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases. Results The mean T/NT ratio of 99mTc-3P4-RGD2 in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of 99mTc-3P4-RGD2 SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of 99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of 99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for 99mTc-3P4-RGD2 SMM (area = 0.851) was higher than that for 99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant. Conclusion 99mTc-3P4-RGD2 SMM does not provide any significant advantage over the established 99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of 99mTc-3P4-RGD2 SMM was significantly higher than that of 99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms. PMID:25250628

Validation of an ergonomic method to withdraw [99mTc] radiopharmaceuticals.

PubMed

Blondeel-Gomes, Sandy; Marie, Solène; Fouque, Julien; Loyeau, Sabrina; Madar, Olivier; Lokiec, François

2017-11-10

The main objective of the present work was to ensure quality of radiopharmaceuticals syringes withdrawn with a "Spinal needle/obturator In-Stopper" system. Methods: Visual examinations and physicochemical tests are performed at T0 and T+4h for [ 99m Tc]albumin nanocolloid and T+7h for [ 99m Tc]eluate, [ 99m Tc] HydroxyMethylene DiPhosphonate and [ 99m Tc]Human Serum Albumin. Microbiological validation was performed according to European pharmacopoeia. Fingertip radiation exposure was evaluated to confirm the safety of the system. Results: Results show stable visual and physicochemical properties. The integrity of the connector was not affected after 30 punctures (no cores). No microbiological contamination was found on tested syringes. Conclusion: The system could be used 30 times. The stability of syringes drawing with this method is guaranteed up to 4 hours for [ 99m Tc]albumin nanocolloid and 7 hours for [ 99m Tc]eluate, [ 99m Tc]HydroxyMethylene DisPhosphonate and [ 99m Tc]Human serum albumin. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

PubMed

Watanabe, N; Oriuchi, N; Sugiyama, S; Kuroki, M; Matsuoka, Y; Tanada, S; Murata, H; Inoue, T; Sasaki, Y

1999-01-01

The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

99mTc-N4-[Tyr3]Octreotate Versus 99mTc-EDDA/HYNIC-[Tyr3]Octreotide: an intrapatient comparison of two novel Technetium-99m labeled tracers for somatostatin receptor scintigraphy.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Maina, Theodosia; Nock, Berthold; vonGuggenberg, Elisabeth; Cordopatis, Paul; Moncayo, Roy

2004-02-01

Tetraamine-[Tyr3]octreotate (Demotate) is a somatostatin (SST) analogue that can be easily labeled with 99mTc at high specific activities and showed promising preclinical properties for SST receptor scintigraphy. This study reports on the first intra-patient comparison of 99mTc-Demotate and another 99mTc-labeled SST analogue, 99mTc-EDDA/HYNIC-TOC (HYNIC-TOC). Five patients with carcinoid tumors (n = 2) and endocrine pancreatic tumors (n = 3) were investigated with both radiopharmaceuticals. 99mTc-Demotate rapidly visualized somatostatin receptor positive tumors as early as 15 minutes post-injection (p.i.) with maximum tumor uptake and tumor/organ ratios already 1 hour p.i. Organs of predominant physiological uptake were the spleen and the kidneys with no intestinal excretion detectable up to 24 hours. 99mTc-Demotate exhibited faster pharmacokinetic properties compared to HYNIC-TOC. Tumor/organ ratios at equivalent time points were higher or comparable for 99mTc-Demotate in three patients with a matching scan result. Equivocal findings were observed in two patients, i.e. comparable uptake behavior in larger lesions with differences in smaller ones. 99mTc-Demotate is a promising agent for somatostatin receptor scintigraphy providing images of excellent quality as early as 1 hour after injection.

Design of an X -band electron linear accelerator dedicated to decentralized 99Mo/99mTc supply: From beam energy selection to yield estimation

NASA Astrophysics Data System (ADS)

Jang, Jaewoong; Yamamoto, Masashi; Uesaka, Mitsuru

2017-10-01

The most frequently used radionuclide in diagnostic nuclear medicine, 99mTc, is generally obtained by the decay of its parent radionuclide, 99Mo. Recently, concerns have been raised over shortages of 99Mo/99mTc, owing to aging of the research reactors which have been supplying practically all of the global demand for 99Mo in a centralized fashion. In an effort to prevent such 99Mo/99mTc supply disruption and, furthermore, to ameliorate the underlying instability of the centralized 99Mo/99mTc supply chain, we designed an X -band electron linear accelerator which can be distributed over multiple regions, whereby 99Mo/99mTc can be supplied with improved accessibility. The electron beam energy was designed to be 35 MeV, at which an average beam power of 9.1 kW was calculated by the following beam dynamics analysis. Subsequent radioactivity modeling suggests that 11 of the designed electron linear accelerators can realize self-sufficiency of 99Mo/99mTc in Japan.

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PubMed

Darr, Andreas M; Opfermann, Thomas; Niksch, Tobias; Driesch, Dominik; Marlowe, Robert J; Freesmeyer, Martin

2013-10-01

The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

Imaging of irradiated liver with Tc-99m-sulfur colloid and Tc-99m-IDA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gelfand, M.J.; Saha, S.; Aron, B.S.

1981-09-01

In three cases, irradiated regions of liver failed to concentrate Tc-99m-sulfur colloid. In two of these three, imaging with Tc-99m-acetanilide iminodiacetic acid (IDA) agents within five days showed near normal hepatic uptake of this hepatobiliary imaging agent. The hepatic parenchymal cells may be imaged with Tc-99m-IDA in some irradiated regions of liver, despite loss of reticuloendothelial cell function.

99mTc-labeling of HYNIC-conjugated cyclic RGDfK dimer and tetramer using EDDA as coligand.

PubMed

Wang, Jianjun; Kim, Young-Seung; Liu, Shuang

2008-03-01

In this study, EDDA (ethylenediamine- N, N'-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC-dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC-tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC-dimer was allowed to react with 99mTcO4 (-) in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC-dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC-dimer)(EDDA)] with high yield (>90%) and high specific activity ( approximately 8.0 Ci/micromol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC-tetramer)(EDDA)] was always <65%. The results from a mixed-ligand experiment show that there is only one EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC-dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC-dimer and HYNIC-tetramer. Surprisingly, [99mTc(HYNIC-dimer)(EDDA)] and [99mTc(HYNIC-tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC-tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.

Method for generating a crystalline .sup.99 MoO.sub.3 product and the isolation .sup.99m Tc compositions therefrom

DOEpatents

Bennett, Ralph G.; Christian, Jerry D.; Kirkham, Robert J.; Tranter, Troy J.

1998-01-01

An improved method for producing .sup.99m Tc compositions. .sup.100 Mo metal is irradiated with photons in a particle (electron) accelerator to produce .sup.99 Mo metal which is dissolved in a solvent. A solvated .sup.99 Mo product is then dried to generate a supply of .sup.99 MoO.sub.3 crystals. The crystals are thereafter heated at a temperature which will sublimate the crystals and form a gaseous mixture containing vaporized .sup.99m TcO.sub.3 and vaporized .sup.99m TcO.sub.2 but will not cause the production of vaporized .sup.99 MoO.sub.3. The mixture is then combined with an oxidizing gas to generate a gaseous stream containing vaporized .sup.99m Tc.sub.2 O.sub.7. Next, the gaseous stream is cooled to a temperature sufficient to convert the vaporized .sup.99m Tc.sub.2 O.sub.7 into a condensed .sup.99m Tc-containing product. The product has high purity levels resulting from the use of reduced temperature conditions and ultrafine crystalline .sup.99 MoO.sub.3 starting materials with segregated .sup.99m Tc compositions therein which avoid the production of vaporized .sup.99 MoO.sub.3 contaminants.

Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)-dipicolylamine) coordination complexes as cell death imaging agents

PubMed Central

wyffels, Leonie; Gray, Brian D.; Barber, Christy; Woolfenden, James M.; Pak, Koon Y.; Liu, Zhonglin

2011-01-01

The aim of this study was the development of 99mTc labeled bis(zinc(II)-dipicolylamine) (Zn2+-DPA) coordination complexes, and the in vivo evaluation of their usefulness as radiotracers for the detection of cell death. DPA ligand 1 was labeled with 99mTc via the 99mTc-tricarbonyl core ([99mTc(CO)3-1]3+) or via HYNIC (99mTc-HYNIC-1) in good radiochemical yields. Highest in vitro stabilities were demonstrated for [99mTc(CO)3-1]3+. A mouse model of hepatic apoptosis (anti-Fas mAb) was used to demonstrate binding to apoptotic cells. 99mTc-HYNIC-1 showed the best targeting of apoptotic hepatic tissue with a 2.2 times higher liver uptake in anti-Fas treated mice as compared to healthy animals. A rat model of ischemia-reperfusion injury was used to further explore the ability of the 99mTc-labeled Zn2+-DPA coordination complexes to target cell death. Selective accumulation could be detected for both tracers in the area at risk, correlating with histological proof of cell death. Area at risk to normal tissue uptake ratios were 3.82 for [99mTc(CO)3-1]3+ and 5.45 for 99mTc-HYNIC-1. PMID:21570306

Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic plaque imaging agent in experimental models.

PubMed

Cao, Wei; Zhang, Yongxue; An, Rui

2006-01-01

The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/- 1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Development of (99m)Tc-Labeled Pyridyl Benzofuran Derivatives To Detect Pancreatic Amylin in Islet Amyloid Model Mice.

PubMed

Yoshimura, Masashi; Ono, Masahiro; Watanabe, Hiroyuki; Kimura, Hiroyuki; Saji, Hideo

2016-06-15

While islet amyloid deposition comprising amylin is one of pathological hallmarks of type 2 diabetes mellitus (T2DM), no useful amylin-imaging probe has been reported. In this study, we evaluated two (99m)Tc-labeled pyridyl benzofuran derivatives as novel amylin-imaging probes using the newly established islet amyloid model mouse. Binding experiments in vitro demonstrated that [(99m)Tc]1 displayed a higher affinity for amylin aggregates than [(99m)Tc]2. Autoradiographic studies using human pancreas sections with T2DM revealed that [(99m)Tc]1 clearly labeled islet amyloid in T2DM pancreatic sections, while [(99m)Tc]2 did not. Although the initial uptake of [(99m)Tc]1 by the normal mouse pancreas was low (0.74%ID/g at 2 min post-injection), [(99m)Tc]1 showed higher retention in the model mouse pancreas than that of the normal mouse, and exhibited strong binding to amylin aggregates in the living pancreas of the model mice. These results suggest that [(99m)Tc]1 is a potential imaging probe targeting islet amyloids in the T2DM pancreas.

Analysis of accumulation of 99mTc-octreotide and 99mTc-EDDA/HYNIC-Tyr3-octreotide in the rat kidneys.

PubMed

Kopecky, Martin; Semecky, Vladimir; Trejtnar, Frantisek; Laznicek, Milan; Laznickova, Alice; Nachtigal, Petr; Decristoforo, Clemens; Mather, Stephen J; Mäcke, Helmut R

2004-02-01

The aim of this study was to compare renal handling and distribution of (99m)Tc-octreotide and (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide (HYNIC-TOC) in rats. In kidney perfusion experiments, the renal clearance value of (99m)Tc-octreotide was three times lower than that of (99m)Tc-EDDA/HYNIC-TOC. The predominant renal excretion of (99m)Tc-EDDA/HYNIC-TOC was associated with a high and long-term renal accumulation up to 48 hrs. Microautoradiographic results indicated that (99m)Tc-EDDA/HYNIC-TOC was retained mainly in the renal medulla within the cells of the collecting ducts and in the surrounding tissue. Lower positivity was found in the proximal and distal tubular cells. We conclude that the mechanism of renal accumulation of somatostatin analogues renal accumulation is complex and that proximal tubular reabsorption is probably not the main mechanism for uptake of (99m)Tc-EDDA/HYNIC-TOC in the kidneys. The presence of the somatostatin receptors, differences in the tonicity level within kidneys and other possible mechanisms could participate in their renal accumulation.

Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

PubMed

Selivanova, Svetlana V; Lavallée, Éric; Senta, Helena; Caouette, Lyne; Sader, Jayden A; van Lier, Erik J; Zyuzin, Alexander; van Lier, Johan E; Guérin, Brigitte; Turcotte, Éric; Lecomte, Roger

2015-10-01

Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required. Thick 100Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using γ-ray spectrometry. The internal radiation dose for 99mTc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. Extracted sodium pertechnetate 99mTc met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched 100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate 99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815% 100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator. Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

An efficient HPLC method for the analysis of isomeric purity of technetium-99m-exametazime and identity confirmation using LC-MS.

PubMed

Vanderghinste, D; Van Eeckhoudt, M; Terwinghe, C; Mortelmans, L; Bormans, G M; Verbruggen, A M; Vanbilloen, H P

2003-08-08

99mTc-exametazime (99mTc-d,l-HMPAO, 99mTc-d,l-hexamethylpropyleneamine oxime) is a neutral rather unstable complex of short-lived 99mTc (t(1/2)=6 h) with the d,l-isomer (mixture of D,D- and L,L-isomers) of a bis-amine bis-oxime tetraligand. It is widely used for measurement of regional cerebral perfusion in nuclear medicine. The meso-isomer (D,L-form) should not be present in a preparation as it is not retained in brain and thus does not provide clinically useful information. Meso-HMPAO is removed from the ligand during the synthesis procedure by repeated recrystallization, but can still be present as impurity in d,l-isomer. Due to the lack of a suitable chromatographic method for analysis of the isomeric purity of 99mTc-exametazime preparations, United States Pharmacopoeia 25 (USP 25) prescribes a biological test in rats for quality control purpose. In this study, we developed a suitable high-performance liquid chromatography (HPLC) method which allows to demonstrate the relative amounts of d,l- and meso-isomer in 99mTc-exametazime and so obviates the need for a biodistribution test in animals as part of the quality control. Due to the low concentrations in which 99mTc-d,l-HMPAO is obtained (typically 2-6 ng/ml), confirmation of the identity of 99mTc-d,l-HMPAO in the monograph of the European Pharmacopoeia is now performed only indirectly by TLC and assessment of its retention time on RP-HPLC. To investigate the potential of radio-LC-MS for assessment of the identity of 99mTc-exametazime, 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO prepared using a Tc-rich eluate were analyzed using a radio-LC-MS system equipped with a time-of-flight mass spectrometer with electrospray ionization. The main peak in the radiometric channel coincided with the molecular ion mass of 99mTc-d,l-HMPAO in the mass spectrometer channel and the measured accurate mass differed only by 0.26 ppm from the theoretical mass. The identity of 99mTc-meso-HMPAO was also confirmed. Thus, radio-LC-MS allowed to obtain strong evidence for the structure of 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO at nanomolar concentration. It is concluded that radio-LC-MS can become a sensitive aid in quality control of "no carrier added" radiopharmaceutical preparations.

Evaluation of technetium-99m decay on Escherichia coli inactivation: effects of physical or chemical agents.

PubMed Central

Silva, C. R.; Valsa, J. O.; Caniné, M. S.; Caldeira-de-Araújo, A.; Bernardo-Filho, M.

1998-01-01

Technetium-99m (99mTc) has been used in nuclear medicine and in biomedical research to label molecular and cellular structures employed as radiotracers. Here, we have evaluated, on a DNA repair proficient Escherichia coli strain, the 99mTc decay inactivation and the influence of the (i) pre-treatment with metal ion chelators or of the (ii) treatment with a free radical scavenger on the protection of the cells against the lethal effect of the 99mTc. As SnCl2 is frequently used as a reducing agent in the 99mTc-labeling process, we have also studied the capability of SnCl2 to alter the biological effects induced by the 99mTc decay. As we are exposed to either chemical or physical agents in the nature, we have decided to study a possible influence of the ultraviolet solar radiation in the biological phenomena induced by the 99mTc decay. Our data point out (i) a very important role of the Auger and/or conversion electrons in the cytotoxicity induced by the 99mTc decay; (ii) SnCl2, the metal ion chelators and the free radical scavenger protect the cells against the lethal effect of the 99mTc; and (iii) near-UV does not alter the lethal effect of the 99mTc decay. PMID:9713950

Report of a nationwide survey on actual administered radioactivities of radiopharmaceuticals for diagnostic reference levels in Japan.

PubMed

Watanabe, Hiroshi; Ishii, Kazunari; Hosono, Makoto; Imabayashi, Etsuko; Abe, Koichiro; Inubushi, Masayuki; Ohno, Kazuko; Magata, Yasuhiro; Ono, Kinya; Kikuchi, Kei; Wagatsuma, Kei; Takase, Tadashi; Saito, Kyoko; Takahashi, Yasuyuki

2016-07-01

The optimization of medical exposure is one of the major issues regarding radiation protection in the world, and The International Committee of Radiological Protection and the International Atomic Energy Agency recommend establishing diagnostic reference levels (DRLs) as tools for dose optimization. Therefore, the development of DRLs based on the latest survey has been required for nuclear medicine-related societies and organizations. This prompted us to conduct a nationwide survey on the actual administered radioactivity to adults for the purpose of developing DRLs in nuclear medicine. A nationwide survey was conducted from November 25, 2014 to January 16, 2015. The questionnaire was sent to all of the 1249 nuclear medicine facilities in Japan, and the responses were collected on a website using an answered form. Responses were obtained from 516 facilities, for a response rate of 41 %. 75th percentile of (99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy, (99m)Tc-HM-PAO, (99m)Tc-ECD and (123)I-IMP: cerebral blood flow scintigraphy, (99m)Tc-Tetrofosmin, (99m)Tc-MIBI and (201)Tl-Cl; myocardial perfusion scintigraphy and (18)F-FDG: oncology PET (in-house-produced or delivery) in representative diagnostic nuclear medicine scans were 932, 937, 763, 775, 200, 831, 818, 180, 235 and 252, respectively. More than 90 % of the facilities were within the range of 50 % from the median of these survey results in representative diagnostic nuclear medicine facilities in Japan. Responses of the administered radioactivities recommended by the package insert, texts and guidelines such as 740 MBq ((99m)Tc-MDP and (99m)Tc-HMDP: bone scintigraphy), 740 MBq ((99m)Tc-ECD and (99m)Tc-HM-PAO: cerebral blood flow scintigraphy) and 740 MBq ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI: myocardial perfusion scintigraphy), etc. were numerous. The administered activity of many radiopharmaceuticals of bone scintigraphy ((99m)Tc-MDP and (99m)Tc-HMDP), cerebral blood flow scintigraphy ((99m)Tc-HM-PAO) and myocardial perfusion scintigraphy ((99m)Tc-Tetrofosmin and (99m)Tc-MIBI), etc. were within the range of the EU DRLs and almost none of the administered radioactivity in Japan exceeded the upper limit of SNMMI standard administered radioactivity. This survey indicated that the administered radioactivity in diagnostic nuclear medicine in Japan had been in the convergence zone and nuclear medicine facilities in Japan show a strong tendency to adhere to the texts and guidelines. Furthermore, the administered radioactivities in Japan were within the range of variation of the EU and the SNMMI administered radioactivities.

Technetium-99m generator system

DOEpatents

Mirzadeh, Saed; Knapp, Jr., Furn F.; Collins, Emory D.

1998-01-01

A .sup.99 Mo/.sup.99m Tc generator system includes a sorbent column loaded with a composition containing .sup.99 Mo. The sorbent column has an effluent end in fluid communication with an anion-exchange column for concentrating .sup.99m Tc eluted from the sorbent column. A method of preparing a concentrated solution of .sup.99m Tc includes the general steps of: a. providing a sorbent column loaded with a composition containing .sup.99 Mo, the sorbent column having an effluent end in fluid communication with an anion-exchange column; b. eluting the sorbent column with a salt solution to elute .sup.99m Tc from the sorbent and to trap and concentrate the eluted .sup.99m Tc on the ion-exchange column; and c. eluting the concentrated .sup.99m Tc from the ion-exchange column with a solution comprising a reductive complexing agent.

Technetium-99m generator system

DOEpatents

Mirzadeh, S.; Knapp, F.F. Jr.; Collins, E.D.

1998-06-30

A {sup 99}Mo/{sup 99m}Tc generator system includes a sorbent column loaded with a composition containing {sup 99}Mo. The sorbent column has an effluent end in fluid communication with an anion-exchange column for concentrating {sup 99m}Tc eluted from the sorbent column. A method of preparing a concentrated solution of {sup 99m}Tc includes the general steps of: (a) providing a sorbent column loaded with a composition containing {sup 99}Mo, the sorbent column having an effluent end in fluid communication with an anion-exchange column; (b) eluting the sorbent column with a salt solution to elute {sup 99m}Tc from the sorbent and to trap and concentrate the eluted {sup 99m}Tc on the ion-exchange column; and (c) eluting the concentrated {sup 99m}Tc from the ion-exchange column with a solution comprising a reductive complexing agent. 1 fig.

A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.

PubMed

Magata, Yasuhiro; Kawaguchi, Takayoshi; Ukon, Misa; Yamamura, Norio; Uehara, Tomoya; Ogawa, Kazuma; Arano, Yasushi; Temma, Takashi; Mukai, Takahiro; Tadamura, Eiji; Saji, Hideo

2004-01-01

C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.

SPECT Imaging of Mice with 99mTc-Radiopharmaceuticals Obtained from 99Mo Produced by 100Mo(n,2n)99Mo and Fission of 235U

NASA Astrophysics Data System (ADS)

Hashimoto, Kazuyuki; Nagai, Yasuki; Kawabata, Masako; Sato, Nozomi; Hatsukawa, Yuichi; Saeki, Hideya; Motoishi, Shoji; Ohta, Masayuki; Konno, Chikara; Ochiai, Kentaro; Kawauchi, Yukimasa; Ohta, Akio; Shiina, Takayuki; Takeuchi, Nobuhiro; Ashino, Hiroki; Nakahara, Yuto

2015-04-01

The distribution of 99mTc-radiopharmaceutical in mouse was determined by single photon emission computed tomography (SPECT) for the first time using 99mTc, which was separated by thermochromatography from 99Mo produced via the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The SPECT image was comparable to that obtained using the fission product 99Mo. Radionuclidic and radiochemical purities of the separated 99mTc and its aluminum concentration met the United States Pharmacopeia regulatory requirements for 99mTc from the fission product 99Mo. These results provide important evidence that the 99mTc-radiopharmaceutical formulated using the (n,2n) 99Mo can be a promising substitute for the fission product 99Mo. The current and forthcoming problem of ensuring a reliable and constant supply of 99Mo in Japan can be partially mitigated.

TC-99m MIBI SPECT imaging in patients with lung carcinoma: is it a functional probe of multidrug resistance genes?

PubMed

Ak, Ilknur; Gülbaş, Zafer; Ocak, Suna; Kaya, Eser; Alataş, Füsun; Vardareli, Erkan; Metintaş, Muzaffer

2007-01-01

Multidrug-resistance (MDR) phenotype concerns altered membrane transport that results in lower cell concentrations of cytotoxic drug in many cancer types, including lung cancer, and is related to the overexpression of a variety of proteins that act as adenosine triphosphate-dependent extrusion pumps. Tc-99m Sestamibi (MIBI) is a transport substrate for P-glycoprotein (Pgp) pump. In this study, we assessed the uptake and clearance of technetium-99m-2-hexakis 2-methoxyisobutylisonitrile (Tc-99m MIBI) from the tumor and its correlation with messenger RNA (mRNA) levels of Pgp, MDR-associated protein (MRP1), and lung resistance protein (LRP) in lung carcinoma. This study was carried out on 19 patients (mean age, 60.1 +/- 2.07 years) with advanced-stage lung carcinoma. The tumor samples obtained by bronchoscopy were assessed to estimate the levels of Pgp, MRP1, and LRP expression on mRNA level by quantitative real-time reverse-transcription polymerase chain reaction. Tc-99m MIBI chest imaging was performed 15 and 180 minutes after injection of 740 MBq Tc-99m MIBI. The early (T/Be) and delayed (T/Bd) Tc-99m MIBI uptakes and washout rate (WR) of Tc-99m MIBI from the tumor were measured. No correlation was found between the T/Be Tc-99m MIBI uptake of tumors (T/Be) and the levels of Pgp mRNA, MRP1 mRNA, and LRP mRNA by reverse-transcription polymerase chain reaction. There was a correlation between the mean T/Bd Tc-99m MIBI uptake and Pgp expression of the tumors (P = 0.001, Spearman rho = - 0.702). There was a correlation between the WR of Tc-99m MIBI from the tumor and Pgp expression of the tumor (P = 0.000, Spearman rho = 0.875). Washout rate of Tc-99m MIBI was not related to the levels of MRP1 mRNA (P = 0.93, Spearman rho = 0.02) or LRP mRNA (P = 0.47, Spearman rho = 0.177). Increased WR of Tc-99m MIBI is related in Pgp over expression of the tumor. Tc-99m MIBI single photon emission computed tomography imaging may be a functional probe of overexpression of Pgp in patients with lung carcinoma. However, Tc-99m MIBI single photon emission computed tomography imaging cannot be used to identify the MDR involved in the MRP1 or LRP in these patients.

Method for generating a crystalline {sup 99}MoO{sub 3} product and the isolation {sup 99m}Tc compositions therefrom

DOEpatents

Bennett, R.G.; Christian, J.D.; Kirkham, R.J.; Tranter, T.J.

1998-09-01

An improved method is described for producing {sup 99m}Tc compositions. {sup 100}Mo metal is irradiated with photons in a particle (electron) accelerator to produce {sup 99}Mo metal which is dissolved in a solvent. A solvated {sup 99}Mo product is then dried to generate a supply of {sup 99}MoO{sub 3} crystals. The crystals are thereafter heated at a temperature which will sublimate the crystals and form a gaseous mixture containing vaporized {sup 99m}TcO{sub 3} and vaporized {sup 99m}TcO{sub 2} but will not cause the production of vaporized {sup 99}MoO{sub 3}. The mixture is then combined with an oxidizing gas to generate a gaseous stream containing vaporized {sup 99m}Tc{sub 2}O{sub 7}. Next, the gaseous stream is cooled to a temperature sufficient to convert the vaporized {sup 99m}Tc{sub 2}O{sub 7} into a condensed {sup 99m}Tc-containing product. The product has high purity levels resulting from the use of reduced temperature conditions and ultrafine crystalline {sup 99}MoO{sub 3} starting materials with segregated {sup 99m}Tc compositions therein which avoid the production of vaporized {sup 99}MoO{sub 3} contaminants. 1 fig.

A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

PubMed

Kim, Myoung Hyoun; Kim, Seul-Gi; Kim, Dae-Weung

2018-06-15

We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent. Copyright © 2018 John Wiley & Sons, Ltd.

Synthesis and evaluation of Tc-99m and fluorescence-labeled elastin-derived peptide, VAPG for multimodal tumor imaging in murine tumor model.

PubMed

Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Seul-Gi; Kim, Dae-Weung

2017-12-01

We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent. Copyright © 2017 John Wiley & Sons, Ltd.

Differential Lung Uptake of 99mTc-HMPAO and 99mTc-Duramycin in the Chronic Hyperoxia Rat Model

PubMed Central

Clough, Anne V.; Audi, Said H.; Haworth, Steven T.; Roerig, David L.

2015-01-01

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury which occur with acute respiratory distress syndrome, for example. Lung uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue while 99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis and/or necrosis. Thus, we investigated changes in lung uptake of these agents in rat exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods Male Sprague-Dawley rats were pre-exposed to either normoxia (21% O2) or hyperoxia (85% O2) for up to 21 days. For imaging, the rats were anesthetized, injected i.v. with either 99mTc-HMPAO or 99mTc-duramycin (37-74 MBq) and planar images were acquired using a high sensitivity modular gamma camera. Subsequently, 99mTc-macroagreggated albumin (37 MBq, diam=10-40 μm) was injected i.v., imaged, and used to define a lung region-of-interest. The lung to background ratio was used as a measure of lung uptake. Results Hyperoxia exposure resulted in a 74% increase in 99mTc-HMPAO lung uptake, which peaked at 7 days and persisted for the 21 days of exposure. 99mTc-duramycin lung uptake was also maximal at 7 days of exposure but decreased to near control levels by 21 days. The sustained elevation of 99mTc-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 days. Conclusion These results suggest the potential use of 99mTc-HMPAO and 99mTc-duramycin as redox and cell-death imaging biomarkers, respectively, for in vivo identification and assessment of different stages of lung injury. PMID:23086010

Design and Evaluation of New Tc-99m-Labeled Lactam Bridge-Cyclized Alpha-MSH Peptides for Melanoma Imaging

PubMed Central

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-01-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex, 99mTc(CO)3-HYNIC-GGNle-CycMSHhex and 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex were 1.0 ± 0.05, 1.2 ± 0.19 and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-peptides, 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h post-injection. 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex were 2.50 and 3.55 at 4 and 24 h post-injection. The melanoma lesions were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex as an imaging probe at 2 h post-injection. Overall, high melanoma uptake coupled with fast urinary clearance of 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future. PMID:23418722

Discordant hepatic uptake between Tc-99m sulfur colloid and Tc-99m DISIDA in hypervitaminosis A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vincent, L.M.; McCartney, W.H.; Mauro, M.A.

1984-02-01

Scintigraphic findings in a patient with biopsy-proven hypervitaminosis A included markedly impaired hepatic uptake of Tc-99m sulfur colloid but essentially normal uptake of Tc-99m DISIDA. This case presents a potential cause for image discordance with these two agents.

Synthesis, 99m Tc-labeling, and preliminary biological evaluation of DTPA-melphalan conjugates.

PubMed

Wang, Jianjun; Yang, Wenjiang; Xue, Jinquan; Zhang, Yanhua; Liu, Yu

2017-12-01

Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of cancer. For the purpose to develop novel 99m Tc-labeled tumor imaging agents with SPECT, MFL was directly labeled by 99m Tc using diethylene triamine pentacetate acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA-MFL and bis-substituted DTPA-2MFL. Radiolabeling was performed in high yield to get 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL, respectively, which were hydrophilic and stable at room temperature. The high initial tumor uptake with retention, good tumor/muscle ratios, and satisfactory scintigraphic images suggested the potential of 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or 99m Tc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress. Copyright © 2017 John Wiley & Sons, Ltd.

Development of Tyrosine-Based Radiotracer 99mTc-N4-Tyrosine for Breast Cancer Imaging

PubMed Central

Kong, Fan-Lin; Ali, Mohammad S.; Rollo, Alex; Smith, Daniel L.; Zhang, Yinhan; Yu, Dong-Fang; Yang, David J.

2012-01-01

The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with 99mTc with high radiochemical purity (>95%). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc-N4 and the clinical gold standard 18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. PMID:22496612

Mammary lymphoscintigraphy with various radiopharmaceuticals in breast cancer.

PubMed

Imoto, S; Murakami, K; Ikeda, H; Fukukita, H; Moriyama, N

1999-10-01

Sentinel node biopsy (SNB) in breast cancer is a promising surgical technique that avoids unnecessary axillary lymph node dissection. To optimize lymphatic mapping with radiopharmaceuticals, mammary lymphoscintigraphy with 30-50 MBq of technetium-99m-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSAD), technetium-99m-human serum albumin (99mTc-HSA), or technetium-99m-tin colloid (99mTc-TC) were investigated in 69 cases of primary breast cancer. Dynamic early images were obtained during the first 30 or 40 minutes, and static delayed images were obtained 6 hours after tracer injection. Hot spots as sentinel lymph nodes (SLNs) appeared in 51 of 69 cases (74%): in early images in 27 cases and in delayed images in 24 cases. SLNs were visualized more frequently in 23 of the 26 cases (88%) treated with 99mTc-HSAD and in 21 of the 24 cases (88%) treated with 99mTc-HSA than in only 7 of the 19 cases (37%) treated with 99mTc-TC. In 26 of the 51 cases, SLNs were identified as faint spots in delayed images. There was a significant difference in the first appearance of SLNs on the lymphoscintiscan between 43 cases of dense breast parenchyma and 26 cases of fatty breast parenchyma. These results suggest that 99mTc-HSAD or 99mTc-HSA is acceptable for lymphatic mapping, but in cases which have faint spots in delayed images or fatty breast parenchyma, gamma probe-guided SNB may result in failure or misleading false-negative SLNs.

Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent 99mTc-Duramycin

PubMed Central

Audi, Said; Li, Zhixin; Capacete, Joseph; Liu, Yu; Fang, Wei; Shu, Laura G.; Zhao, Ming

2013-01-01

Introduction 99mTc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between 99mTc-Duramycin and the target tissue. Methods High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague Dawley rats. Target binding and biodistribution of 99mTc-duramycin was captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of 99mTc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of 99mTc-Duramycin in normal and ischemic myocardial tissue. Results 99mTc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to 99mTc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for 99mTc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9 fold reduction in binding affinity. Conclusion 99mTc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of 99mTc-Duramycin as a novel PE-binding agent. PMID:22534031

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of (99m)Tc versus (188)Re.

PubMed

Freudenberg, Robert; Wendisch, Maria; Runge, Roswitha; Wunderlich, Gerd; Kotzerke, Jörg

2012-12-01

Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of (188)Re-perrhenate and (99m)Tc-pertechnetate on cellular survival. Rat thyroid PC Cl3 cells in culture were incubated with (188)Re or (99m)Tc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified. Dose effect curves were established for (188)Re and (99m)Tc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and (188)Re reduced cell survival more efficiently than (99m)Tc. A(37), the activity that is necessary to yield 37% cell survival was 14 MBq/ml for (188)Re and 480 MBq/ml for (99m)Tc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A(37) was reduced by 30% for the beta-emitter and by 95% for (99m)Tc. The dose D(37) that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides. Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular (99m)Tc yielded a dose increase that was higher compared to (188)Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non-uniform lognormal radionuclide uptake.

Macrocyclic triamine derived glucose analogues for 99m Tc(CO)3 labeling: synthesis and biological evaluation as potential tumor-imaging agents.

PubMed

Liu, Teli; Gan, Qianqian; Zhang, Junbo

2017-02-01

[ 99m Tc(CO) 3 (H 2 O) 3 ] + has attracted great attention among 99m Tc-labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to produce stable complex. In this study, two novel 1, 5, 9-triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose-azides with alkyne-[12]aneN 3 via the so-called click chemistry and radiolabeled with [ 99m Tc(CO) 3 (H 2 O) 3 ] + to form 99m Tc(CO) 3 -6 (C-1-substituted complex) and 99m Tc(CO) 3 -7 (C-2-substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99m Tc(CO) 3 -7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99m Tc-radiolabeled glucose derivatives, 99m Tc(CO) 3 -7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor-imaging agent. © 2017 John Wiley & Sons A/S.

In vivo imaging of tumour angiogenesis in mice with the alpha(v)beta (3) integrin-targeted tracer 99mTc-RAFT-RGD.

PubMed

Sancey, Lucie; Ardisson, Valérie; Riou, Laurent M; Ahmadi, Mitra; Marti-Batlle, Danièle; Boturyn, Didier; Dumy, Pascal; Fagret, Daniel; Ghezzi, Catherine; Vuillez, Jean-Philippe

2007-12-01

The molecular imaging of tumour neoangiogenesis currently represents a major field of research for the diagnostic and treatment strategy of solid tumours. Endothelial cells from tumour neovessels overexpress the alpha(v)beta(3) integrin, which selectively binds to Arg-Gly-Asp (RGD)-containing peptides. We evaluated the potential of the novel radiotracer (99m)Tc-RAFT-RGD for the non-invasive molecular imaging of alpha(v)beta(3) integrin expression in mice models of tumour development. (99m)Tc-RAFT-RGD, (99m)Tc-cRGD (specific control) and (99m)Tc-RAFT-RAD (non-specific control) were injected intravenously to mice bearing B16F0 or TS/A-pc tumours. In vivo whole-body tomographic imaging and post-mortem biodistribution studies were performed 60 min following tracer injection. Adjacent tumour slices were used to compare the localisation of neovessels from immunostaining and the pattern of (99m)Tc-RAFT-RGD uptake from autoradiographic ex vivo imaging. Biodistribution studies indicated that (99m)Tc-RAFT-RGD tumour uptake was significantly higher than that of (99m)Tc-RAFT-RAD in B16F0 (2.4+/-0.5 vs 1.0+/-0.1%ID/g, respectively) and in TS/A-pc tumours (2.7+/-0.8 vs 0.7+/-0.1%ID/g, respectively). Immunohistochemical and autoradiographic studies indicated that (99m)Tc-RAFT-RGD intratumoural uptake preferentially occurred in angiogenic areas. Tomographic imaging allowed tumour visualisation following injection of (99m)Tc-RAFT-RGD and (99m)Tc-cRGD with similar tumour-to-contralateral muscle (T/CM) ratios in B16F0 and in TS/A-pc tumours whereas (99m)Tc-RAFT-RAD T/CM ratios did not allow tumour imaging. In accordance with the higher level of alpha(v)beta(3) integrin expression on TS/A-pc tumours than on B16F0 tumours as determined from western blot and immunoprecipitation analyses, the (99m)Tc-RAFT-RGD T/CM ratio was significantly higher in TS/A-pc than in B16F0 tumours. (99m)Tc-RAFT-RGD allowed the in vivo imaging of alpha(v)beta(3) integrin tumour expression.

Quantitative analysis of [99mTc]C2A-GST distribution in the area at risk after myocardial ischemia and reperfusion using a compartmental model.

PubMed

Audi, Said; Poellmann, Michael; Zhu, Xiaoguang; Li, Zhixin; Zhao, Ming

2007-11-01

It was recently demonstrated that the radiolabeled C2A domain of synaptotagmin I accumulates avidly in the area at risk after ischemia and reperfusion. The objective was to quantitatively characterize the dynamic uptake of radiolabeled C2A in normal and ischemically injured myocardia using a compartmental model. To induce acute myocardial infarction, the left descending coronary artery was ligated for 18 min, followed by reperfusion. [99mTc]C2A-GST or its inactivated form, [99mTc]C2A-GST-NHS, was injected intravenously at 2 h after reperfusion. A group of four rats was sacrificed at 10, 30, 60 and 180 after injection. Uptake of [99mTc]C2A-GST and [99mTc]C2A-GST-NHS in the area at risk and in the normal myocardium were determined by gamma counting. A compartmental model was developed to quantitatively interpret myocardial uptake kinetic data. The model consists of two physical spaces (vascular space and tissue space), with plasma activity as input. The model allows for [99mTc]C2A-GST and [99mTc]C2A-GST-NHS diffusion between vascular and tissue spaces, as well as for [99mTc]C2A-GST sequestration in vascular and tissue spaces via specific binding. [99mTc]C2A-GST uptake in the area at risk was significantly higher than that for [99mTc]C2A-GST-NHS at all time points. The compartmental model separated [99mTc]C2A-GST uptake in the area at risk due to passive retention from that due to specific binding. The maximum amount of [99mTc]C2A-GST that could be sequestered in the area at risk due to specific binding was estimated at a total of 0.048 nmol/g tissue. The rate of [99mTc]C2A-GST sequestration within the tissue space of the area at risk was 0.012 ml/min. Modeling results also revealed that the diffusion rate of radiotracer between vascular and tissue spaces is the limiting factor of [99mTc]C2A-GST sequestration within the tissue space of the area at risk. [99mTc]C2A-GST is sequestered in the ischemically injured myocardium in a well-defined dynamic profile. Model parameters will be valuable indicators for gauging and guiding the development of future-generation molecular probes.

Diversification of 99Mo/99mTc separation: non–fission reactor production of 99Mo as a strategy for enhancing 99mTc availability.

PubMed

Pillai, Maroor R A; Dash, Ashutosh; Knapp, Furn F Russ

2015-01-01

This paper discusses the benefits of obtaining (99m)Tc from non-fission reactor-produced low-specific-activity (99)Mo. This scenario is based on establishing a diversified chain of facilities for the distribution of (99m)Tc separated from reactor-produced (99)Mo by (n,γ) activation of natural or enriched Mo. Such facilities have expected lower investments than required for the proposed chain of cyclotrons for the production of (99m)Tc. Facilities can receive and process reactor-irradiated Mo targets then used for extraction of (99m)Tc over a period of 2 wk, with 3 extractions on the same day. Estimates suggest that a center receiving 1.85 TBq (50 Ci) of (99)Mo once every 4 d can provide 1.48-3.33 TBq (40-90 Ci) of (99m)Tc daily. This model can use research reactors operating in the United States to supply current (99)Mo needs by applying natural (nat)Mo targets. (99)Mo production capacity can be enhanced by using (98)Mo-enriched targets. The proposed model reduces the loss of (99)Mo by decay and avoids proliferation as well as waste management issues associated with fission-produced (99)Mo.

Improved synthesis and biological evaluation of Tc-99m radiolabeled AMO for miRNA imaging in tumor xenografts.

PubMed

Kang, Lei; Fan, Zhongyi; Sun, Hongwei; Feng, Yingying; Ma, Chao; Yan, Ping; Zhang, Chunli; Ma, Huan; Hao, Pan; Chen, Xueqi; Zheng, Zhibing; Xu, Xiaojie; Wang, Rongfu

2015-01-01

MicroRNAs (miRNAs) have been considered as important biomarkers for malignant tumors. In this study, we introduced an improved (99m)Tc labeling method for noninvasive visualization of overexpressed miRNAs in tumor-bearing mice. Anti-miRNA-21 oligonucleotide (AMO) with partial 2'-O-methyl and phosphorothioate modification was designed and chemically synthesized. After conjugated with NHS-MAG3, AMO was labeled with (99m)Tc. Optimization was made to shorten reaction time and to improve labeling efficiency. Labeling efficiency was 97%, and specific activity was 2.78 MBq/ng. During 12 h, (99m)Tc-AMO showed no significant degradation by gel electrophoresis. Its radiochemical purity was stable, between 95.8% and 99.1%. Further, (99m)Tc-AMO decreased the level of miR-21 and increased the expression of PTEN protein at cellular level, shown by qRT-PCR and Western blot. Fluorescent protein labeled AMO displayed specific distribution and good stability in tumor cells. After the administration in tumor-bearing mice, (99m)Tc-AMO showed more radioactive uptake in the miR-21 over-expressed tumors than scramble control. Biodistribution results further proved the significant difference of tumor uptake between (99m)Tc-AMO and (99m)Tc-control. Therefore, this study presents an improved method with shorten time to prepare a (99m)Tc radiolabeled AMO. In addition, it supports the role of (99m)Tc-AMO for noninvasive visualization of miR-21 in malignant tumors. Copyright © 2015 John Wiley & Sons, Ltd.

Detection of bacterial infection by a technetium-99m-labeled peptidoglycan aptamer.

PubMed

Ferreira, Iêda Mendes; de Sousa Lacerda, Camila Maria; Dos Santos, Sara Roberta; de Barros, André Luís Branco; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

2017-09-01

Nuclear medicine clinicians are still waiting for the optimal scintigraphic imaging agents capable of distinguishing between infection and inflammation, and between fungal and bacterial infections. Aptamers have several properties that make them suitable for molecular imaging. In the present study, a peptidoglycan aptamer (Antibac1) was labeled with 99m Tc and evaluated by biodistribution studies and scintigraphic imaging in infection-bearing mice. Labeling with 99m Tc was performed by the direct method and the complex stability was evaluated in saline, plasma and in the molar excess of cysteine. The biodistribution and scintigraphic imaging studies with the 99m Tc-Antibac1 were carried out in two different experimental infection models: Bacterial-infected mice (S. aureus) and fungal-infected mice (C. albicans). A 99m Tc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control for both models. Radiolabeling yields were superior to 90% and 99m Tc-Antibac1 was highly stable in presence of saline, plasma, and cysteine up to 6h. Scintigraphic images of S. aureus infected mice at 1.5 and 3.0h after 99m Tc-Antibac1 injection showed target to non-target ratios of 4.7±0.9 and 4.6±0.1, respectively. These values were statistically higher than those achieved for the 99m Tc-library at the same time frames (1.6±0.4 and 1.7±0.4, respectively). Noteworthy, 99m Tc-Antibac1 and 99m Tc-library showed similar low target to non-target ratios in the fungal-infected model: 2.0±0.3 and 2.0±0.6for 99m Tc-Antibac1 and 2.1±0.3 and 1.9 ± 0.6 for 99m Tc-library, at the same times. These findings suggest that the 99m Tc-Antibac1 is a feasible imaging probe to identify a bacterial infection focus. In addition, this radiolabeled aptamer seems to be suitable in distinguishing between bacterial and fungal infection. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study.

PubMed

Monteiro, Liziane O F; Fernandes, Renata S; Oda, Caroline M R; Lopes, Sávia C; Townsend, Danyelle M; Cardoso, Valbert N; Oliveira, Mônica C; Leite, Elaine A; Rubello, Domenico; de Barros, André L B

2018-01-01

A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m ( 99m Tc). Biodistribution studies and scintigraphic images were performed after intravenous administration of 99m Tc-PTX, 99m Tc-SpHL-PTX and 99m Tc-SpHL-folate-PTX into healthy and tumor-bearing mice. High radiochemical purity (>98%) and in vitro stability (>90%) were achieved for both liposome formulations. The pharmacokinetic properties of 99m Tc-SpHL-DTPA-PTX and 99m Tc-SpHL-folate-DTPA-PTX decreased in a monophasic manner showing half-life of 400.1 and 541.8min, respectively. Scintigraphic images and biodistribution studies showed a significant uptake in liver, spleen and kidneys, demonstrating these routes as way for excretion. At 8h post-injection, the liposomal tumor uptake was higher than 99m Tc-PTX. Interesting, 4h after administration, the liposome folate coated showed higher tumor-to-muscle ratio than 99m Tc-SpHL-DTPA-PTX and 99m Tc-PTX. In conclusion, the liposomal systems, showed high tumor uptake by scintigraphic images, especially the 99m Tc-SpHL-folate-DTPA-PTX that showed a sustained and higher tumor-to-muscle ratio than non-functionalized liposome, which indicate its feasibility as a PTX delivery system to folate positive tumors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Nuclear medicine imaging of locally advanced laryngeal and hypopharyngeal cancer

NASA Astrophysics Data System (ADS)

Medvedeva, A.; Chernov, V.; Zeltchan, R.; Sinilkin, I.; Bragina, O.; Chijevskaya, S.; Choynzonov, E.; Goldberg, A.

2017-09-01

The diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. A total of 40 patients with histologically verified laryngeal and hypopharyngeal cancer and 20 patients with benign laryngeal lesions were included into the study. Submucosal injections of 99mTc-MIBI and 99mTc-Alotech were made around the tumor. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-MIBI. Sentinel lymph nodes (SLNs) were detected in 26 patients. In 18 hours after the injection of 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17%) of the 12 patients. Twenty eight SLNs were detected by SPECT and 31 SLNs were identified using the intraoperative gamma probe. The percentage of 99mTc-Alotech in the SLN was 5-10% of the radioactivity in the injection site by SPECT and 18-33% by intraoperative gamma probe detection. Thus, SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specificity and accuracy of this technique were 95%, 80% and 92%, respectively. The use of 99mTc-Alotech for the detection of SLNs in patients with laryngeal/hypopharyngeal cancer is characterized by 92.8% sensitivity.

Imaging of Cerebral Amyloid Angiopathy with Bivalent 99mTc-Hydroxamamide Complexes

NASA Astrophysics Data System (ADS)

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-01

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer’s disease (AD). We previously reported 99mTc-hydroxamamide (99mTc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for 99mTc-Ham complexes, and all 99mTc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent 99mTc-Ham complexes ([99mTc]SB2A and [99mTc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the 99mTc-Ham complex.

Comparison of LDPI to SPECT perfusion imaging using (99m)Tc-sestamibi and (99m)Tc-pyrophosphate in a murine ischemic hind limb model of neovascularization.

PubMed

Hendrikx, Geert; Vries, Mark H; Bauwens, Matthias; De Saint-Hubert, Marijke; Wagenaar, Allard; Guillaume, Joël; Boonen, Levinia; Post, Mark J; Mottaghy, Felix M

2016-12-01

We aimed to determine the accuracy of laser Doppler perfusion imaging (LDPI) in an animal model for hind limb ischemia. We used a murine (C57Bl/6 mice) ischemic hind limb model in which we compared LDPI with the clinically used (99m)Tc-sestamibi SPECT perfusion imaging (n = 7). In addition, we used the SPECT tracer (99m)Tc-pyrophosphate ((99m)Tc-PyP) to image muscular damage (n = 6). LDPI indicated a quick and prominent decrease in perfusion immediately after ligation, subsequently recovering to 21.9 and 25.2 % 14 days later in the (99m)Tc-sestamibi and (99m)Tc-PyP group, respectively. (99m)Tc-sestamibi SPECT scans also showed a quick decrease in perfusion. However, nearly full recovery was reached 7 days post ligation. Muscular damage, indicated by the uptake of (99m)Tc-PyP, was highest at day 3 and recovered to baseline levels at day 14 post ligation. Postmortem histology supported these findings, as a significantly increased collateral diameter was found 7 and 14 days after ligation and peak macrophage infiltration and TUNEL positivity was found on day 3 after ligation. Here, we indicate that LDPI strongly underestimates perfusion recovery in a hind limb model for profound ischemia.

Imaging of Cerebral Amyloid Angiopathy with Bivalent (99m)Tc-Hydroxamamide Complexes.

PubMed

Iikuni, Shimpei; Ono, Masahiro; Watanabe, Hiroyuki; Matsumura, Kenji; Yoshimura, Masashi; Kimura, Hiroyuki; Ishibashi-Ueda, Hatsue; Okamoto, Yoko; Ihara, Masafumi; Saji, Hideo

2016-05-16

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported (99m)Tc-hydroxamamide ((99m)Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for (99m)Tc-Ham complexes, and all (99m)Tc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent (99m)Tc-Ham complexes ([(99m)Tc]SB2A and [(99m)Tc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the (99m)Tc-Ham complex.

A system of {sup 99m}Tc production based on distributed electron accelerators and thermal separation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, R.G.; Christian, J.D.; Petti, D.A.

1999-04-01

A system has been developed for the production of {sup 99m}Tc based on distributed electron accelerators and thermal separation. The radioactive decay parent of {sup 99m}Tc, {sup 99}Mo, is produced from {sup 100}Mo by a photoneutron reaction. Two alternative thermal separation processes have been developed to extract {sup 99m}Tc. Experiments have been performed to verify the technical feasibility of the production and assess the efficiency of the extraction processes. A system based on this technology enables the economical supply of {sup 99m}Tc for a large nuclear pharmacy. Twenty such production centers distributed near major metropolitan areas could produce the entiremore » US supply of {sup 99m}Tc at a cost less than the current subsidized price.« less

Preclinical evaluation of 99mTc(CO)3-aspartic-N-monoacetic acid, 99mTc(CO)3(ASMA), a new renal radiotracer with pharmacokinetic properties comparable to 131I-OIH

PubMed Central

Lipowska, Malgorzata; Klenc, Jeffrey; Marzilli, Luigi G.; Taylor, Andrew T.

2014-01-01

In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to PAH and superior to those of both 99mTc-MAG3 and 131I-OIH, we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid ligand, 99mTc(CO)3(ASMA). The ASMA ligand features two carboxyl groups and an amine function for the coordination of the {99mTc(CO)3}+ core as well as a dangling carboxylate to facilitate rapid renal clearance. Methods rac-ASMA and L-ASMA were labeled with a 99mTc-tricarbonyl precursor and radiochemical purity of the labeled products was determined by HPLC. Using 131I-OIH as an internal control, we evaluated biodistribution in normal rats with 99mTc(CO)3(ASMA) isomers and in rats with renal pedicle ligation with 99mTc(CO)3(rac-ASMA). Clearance studies were conducted in 4 additional rats. In vitro radiotracer stability was determined in PBS buffer pH 7.4 and in challenge studies with cysteine and histidine. 99mTc(CO)3(ASMA) metabolites in urine were analyzed by HPLC. Results Both 99mTc(CO)3(ASMA) preparations had > 99% radiochemical purity and were stable in PBS buffer pH 7.4 for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, % injected dose in urine at 10 and 60 min for both preparations averaged 103% and 106% that of 131I-OIH, respectively. The renal clearances of 99mTc(CO)3(rac-ASMA) and 131I-OIH were comparable (P = 0.48). The tracer was excreted unchanged in the urine, proving its in vivo stability. In pedicle-ligated rats, 99mTc(CO)3(rac-ASMA) had less excretion into the bowel (P < 0.05) and was better retained in the blood (P < 0.05) than 131I-OIH. Conclusion Both 99mTc(CO)3(ASMA) complexes have pharmacokinetic properties in rats comparable to or superior to those of 131I-OIH, and human studies are warranted for their further evaluation. PMID:22717977

Supine lung clearance of Tc-99m DTPA and HMPAO aerosols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chia-Hung Kao; Hui-Tzu Lin; Shu-Ling Yu

1995-07-01

The speed of Tc-99m DTPA/HMPAO radioaerosol clearance from the lungs that is represented as a slope from lungs to blood was measured in 23 male normal controls using commercial lung radioaerosol delivery units in the supine position in order to avoid the influences of gravity. The right lung was selected and three regions of interest were created for equal subdivisions of the upper, middle, and lower third. The results show that the clearance of Tc-99m DTPA/HMPAO aerosols in the upper lung is lowest. The difference between upper and lower lungs for Tc-99m DTPA/HMPAO aerosol clearances are significant. The clearance ofmore » Tc-99m DTPA aerosols was significantly faster than those of Tc-99m HMPAO in any region. The authors conclude that, although the effect of gravity disappears in the supine position in our study, the differences of aerosol clearance in different regions are still significant. Lipophilic Tc-99m HMPAO aerosols were slower than those of hydrophilic Tc-99m DTPA, which suggests there are at least two different mechanisms. 22 refs., 2 figs., 1 tab.« less

[Gastrointestinal bleeding from capillary hemangioma of the ileum detected by 99mTc-HSAD scintigraphy].

PubMed

Asano, Y; Ishii, K; Sagiuchi, T; Aoki, Y; Yanaihara, H; Hayakawa, K

2001-05-01

It has been well-known that technetium-99m-human serum albumin-diethylenetriaminepenta-acetic acid (99mTc-HSAD) scintigraphy is useful for diagnosis of the localization of the gastrointestinal arterial or venous bleeding. In this report, we describe a case of venous bleeding from capillary hemangioma of the ileum end detected by 99mTc-HSAD scintigraphy. This patient was a 9-year-old girl with severe anemia. Gastrointestinal bleeding was suspected from her clinical course and laboratory tests. Immediately after melena occurred, 99mTc-HSAD scintigraphy showed the extravasation of RI suggesting gastrointestinal bleeding in the ileum end. Abdominal angiography immediately after 99mTc-HSAD scintigraphy, however, could not show the extravasation of contrast agent. Because the condition of the patient became worse, laparotomy was performed on the basis of 99mTc-HSAD scintigraphy findings. At surgery, venous bleeding from capillary hemangioma in the ileum end was observed. It was suggested that 99mTc-HSAD scintigraphy was very useful for identifying the gastrointestinal venous bleeding.

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

PubMed

Wallace, Anne M; Han, Linda K; Povoski, Stephen P; Deck, Kenneth; Schneebaum, Schlomo; Hall, Nathan C; Hoh, Carl K; Limmer, Karl K; Krontiras, Helen; Frazier, Thomas G; Cox, Charles; Avisar, Eli; Faries, Mark; King, Dennis W; Christman, Lori; Vera, David R

2013-08-01

Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

Poor accumulation of technetium-99m glucoheptonate in sarcoidosis and other diffuse infiltrative lung diseases as compared with gallium-67 citrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorne, M.; Sahlstroem, K.A.; Alanko, K.

1988-02-01

Forty-two patients with diffuse infiltrative lung diseases were imaged with Ga-67 citrate and Tc-99m glucoheptonate (GH). Twenty patients had sarcoidosis, six had fibrosis, six had tuberculosis, nine had lung infiltration, and one had pleural empyema. The main difference between Ga-67 and Tc-99m GH was the much greater uptake of Ga-67 in sarcoidosis than that of Tc-99m GH. Fifteen patients with sarcoidosis had positive Ga-67 scans but only six had positive Tc-99m GH scans. The results in other diffuse infiltrative lung diseases were almost equal with Ga-67 and Tc-99m GH. Although Tc-99m GH is less expensive and simpler to use, itmore » is not an adequate substitute for Ga-67 in diffuse infiltrative lung diseases.« less

[Assessment of myocardial perfusion and left ventricular function with 99mTc-PPN 1011].

PubMed

Kumita, S; Mizumura, S; Oishi, T; Kumazaki, T; Sano, J; Yamazaki, Y; Munakata, K

1993-04-01

First-pass radionuclide angiography (FPRNA) was performed with the new myocardial perfusion agent 99mTc-1,2,bis[bis(2-ethoxyethyl)phosphino] ethane (99mTc-PPN 1011) on stress and at rest. One hour after that, myocardial perfusion was counted by 99mTc-PPN 1011 SPECT. Left ventricular ejection fraction (LVEF) obtained by FPRNA correlated with that by multigated image with 99mTc-HSAD (r = 0.94, n = 11). The reduction of left ventricular function under the exercise (delta LVEF) and the increase of severity score (delta Severity score) have a good relation (r = 0.88) in 7 patients with prior myocardial infarction. Thus 99mTc-PPN 1011 appears to be an ideal radiopharmaceutical for evaluation of ventricular function and myocardial perfusion.

Comparative analysis of 99mTc-depreotide and 99mTc-EDDA/HYNIC-TOC thorax scintigrams acquired for the purpose of differential diagnosis of solitary pulmonary nodules.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-01-01

Aiming at comparison of diagnostic efficacy of 2 radiopharmaceuticals: 99mTc-depreotide (Neospect, Amersham) and 99mTc-EDDA/HYNIC-Tyr3-octreotide (Tektrotyd, Polatom), in differentiation between malignant and benign etiology of solitary pulmonary nodules (SPNs), radionuclide studies with 2 radiotracers were performed in 18 patients. For both radiopharmaceuticals the same acquisition and processing protocols were applied. Studies were acquired with SPECT technique, after administration of 740 MBq of activity. Scintigrams were assessed visually, as: positive (+), equivocal (+/-) and negative (-). Additionally, uptake intensity of both radiotracers in nodules was assessed semiquantitatively, using a tumour-to-background ratio. Verification of scintigraphic results was based in 14 cases upon a pathological examination of tumour samples (histopathology) and in the remaining 4 - on clinical observation and bacteriological studies. Normal scintigrams obtained with both radiopharmaceuticals differed significantly. 99mTc-depreotide was markedly accumulated in spine, sternum, ribs and lungs (mean lung/heart ratio = 2.2). This accumulation was not observed on 99mTc- -EDDA/HYNIC-TOC scintigrams (mean lung/heart ratio = 0.7). In 6 patients a malignant etiology--lung cancer--was revealed (5--adenocarcinoma, 1--squamous cell) and the other 12 cases turned out to be benign (4 hamartomas, 3 tuberculomas, a tuberculous infiltrate, an alien body with inflammatory reaction, a hyperplasia of lymphatic tissue and 2 cases of unknown etiology, from which one had a stable size and the other resolved during a 6 month observation period). In all 6 cases of lung cancer positive results were obtained with both tracers. Moreover, in 2 patients metastases in mediastinum could be observed on scintigrams obtained with both radiopharmaceuticals. From among 12 cases of benign etiology 6 99mTc-depreotide scintigrams were true negative, 1--equivocal and 5--false positive, whereas 6 99mTc-EDDA/HYNIC-TOC scintigrams were true negative, 4--equivocal and 2 false positive. Moreover, 99mTc-depreotide additionally revealed mediastinal and hilar lesions in 9 patients with benign lesions and 99mTc-EDDA/HYNIC-TOC - in 8. A visual comparison of scintigrams revealed a higher quality of 99mTc-Depreotide images in comparison with 99mTc-EDDA/HYNIC-TOC ones. 99mTc-Depreotide showed a higher than 99mTc-EDDA/HYNIC-TOC accumulation in lung tumours compared with blood pool (heart) - 4.5 (s.d. 1.05) and 1.8 (s.d. 0.29), respectively (p < 0.05). However, mean values of tumour-to-lung-background ratio were equal for both radiotracers (2.2 in malignant and 1.4 in benign lesions, respectively). A statistically significantly higher non-uniformity of counts inside lung background regions was found on 99mTc-EDDA/HYNIC-TOC scintigrams than on 99mTc-depreotide ones (16.4% vs. 11.4%; p < 0.01). Although both radiopharmaceuticals show similar diagnostic efficacy in differentiation of SPNs, a tendency toward a higher number of false positive results on 99mTc-depreotide scintigrams probably leads to a lower specificity. Better statistical quality of 99mTc-depreotide scintigrams facilitates their interpretation and a distinct outline of lungs simplify localization of lesions. A substantial number of false positive lesions in mediastinal and hilar regions in patients without a neoplastic process hamper the usefulness of both radiotracers for effective detection of lung cancer metastases to lymph nodes.

Design and evaluation of new Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptides for melanoma imaging.

PubMed

Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

2013-04-01

The purpose of this study was to examine the melanoma targeting and imaging properties of new (99m)Tc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) peptides were synthesized, and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc-MAG3-GGNle-CycMSH(hex), (99m)Tc-AcCG3-GGNle-CycMSH(hex), (99m)Tc(CO)3-HYNIC-GGNle-CycMSH(hex), and (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice at 2 h postinjection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were further examined because of its high melanoma uptake and fast urinary clearance. The IC50 values of MAG3-GGNle-CycMSH(hex), AcCG3-GGNle-CycMSH(hex), and HYNIC-GGNle-CycMSH(hex) were 1.0 ± 0.05, 1.2 ± 0.19, and 0.6 ± 0.04 nM in B16/F1 melanoma cells, respectively. Among these four (99m)Tc-peptides, (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) exhibited the highest melanoma uptake (14.14 ± 4.90% ID/g) and fastest urinary clearance (91.26 ± 1.96% ID) at 2 h postinjection. (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) showed high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) were 2.50 and 3.55 at 4 and 24 h postinjection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) as an imaging probe at 2 h postinjection. Overall, high melanoma uptake coupled with fast urinary clearance of (99m)Tc(EDDA)-HYNIC-GGNle-CycMSH(hex) highlighted its potential for metastatic melanoma detection in the future.

Evaluation of 99mTc-3PRGD2 integrin receptor imaging in hepatocellular carcinoma tumour-bearing mice: comparison with 18F-FDG metabolic imaging.

PubMed

Zheng, Jieling; Miao, Weibing; Huang, Chao; Lin, Haoxue

2017-07-01

Our study was designed to explore the utility of 99m Tc-HYNIC-PEG 4 -E[PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD 2 ) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99m Tc-3PRGD 2 integrin receptor imaging and 2-18-fluoro-2-deoxy-D-glucose ( 18 F-FDG) metabolic imaging in a nude mouse model. 99m Tc-3PRGD 2 was synthesized using a HYNIC-3PRGD 2 lyophilized kit with 99m TcO 4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 10 7 /ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99m Tc-3PRGD 2 . Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99m Tc-3PRGD 2 , to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99m Tc-3PRGD 2 and 37 MBq of 18 F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99m Tc-3PRGD 2 and 18 F-FDG. The biodistribution study first validated that the tumour uptake of 99m Tc-3PRGD 2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99m Tc-3PRGD 2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99m Tc-3PRGD 2 integrin receptor imaging was more sensitive than 18 F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of 99m Tc-3PRGD 2 was consistently higher than that of 18 F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of 18 F-FDG was higher than that of 99m Tc-3PRGD 2 . Our study demonstrated that 99m Tc-3PRGD 2 is a valuable tumour molecular probe for the detection of early stage HCC compared with 18 F-FDG, meriting further investigation of 99m Tc-3PRGD 2 as a novel SPECT tracer for tumour imaging.

Phenolic aminocarboxylate chelates of 99mTc as hepatobiliary agents.

PubMed

Hunt, F C; Maddalena, D J; Wilson, J G; Bautovich, G J

1986-01-01

A series of alkyl- and halogen-substituted derivatives of ethylenediamine di[o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis[2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) were complexed with 99mTc and their biodistribution was determined in rats. All complexes displayed substantial hepatobiliary excretion; of each series, 99mTc-Br-EDDHA and 99mTc-di-Cl-HBED had the maximum amount in the gastrointestinal tract. Scintigraphic studies of 99mTc-Cl-EDDHA in dogs revealed prompt imaging of the liver followed by imaging of the gall bladder as the complex was excreted into the bile.

Renal damage detected by DMSA, despite normal renal ultrasound, in children with febrile UTI.

PubMed

Bush, N C; Keays, M; Adams, C; Mizener, K; Pritzker, K; Smith, W; Traylor, J; Villanueva, C; Snodgrass, W T

2015-06-01

2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children. Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function < 44%. We calculated sensitivity, specificity, positive and negative predictive values, and false negative rates of RBUS compared to DMSA. 618 patients (79% female), median age 3.4 years, were referred for FUTIs. Of the 512 (83%) with normal RBUS, 99 (19%) had abnormal DMSA. Children with normal RBUS after their first FUTI had abnormal DMSA in 15/151 (10%) aged ≤ 24 months and 23/119 (19%) aged > 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS. After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

A new approach for manufacturing and processing targets to produce 99mTc with cyclotrons

NASA Astrophysics Data System (ADS)

Matei, L.; McRae, G.; Galea, R.; Niculae, D.; Craciun, L.; Leonte, R.; Surette, G.; Langille, S.; Louis, C. St.; Gelbart, W.; Abeysekera, B.; Johnson, R. R.

2017-06-01

The most important radioisotope for nuclear medicine is 99mTc. After the supply crisis of 99Mo starting in 2008, the availability of 99mTc became a worldwide concern. Alternative methods for producing the medical imaging isotope 99mTc are actively being developed around the world. The reaction 100Mo(p, 2n)99mTc provides a direct route that can be incorporated into routine production in nuclear medicine centers that possess medical cyclotrons for production of other isotopes, such as those used for Positron Emission Tomography. This paper describes a new approach for manufacturing targets for the (p, 2n) nuclear reaction on 100Mo and the foundation for the subsequent commercial separation and purification of the 99mTc produced. Two designs of targets are presented. The targets used to produce 99mTc are subject to a number of operational constraints.They must withstand the temperatures generated by the irradiation, accommodate temperature gradients from cooling system of the target, must be resilient and must be easily post-processed to separate the 99mTc. After irradiation, the separation of Tc from Mo was carried out using an innovative two-step approach. The process described in this paper can be automated with modules that easily fit in standard production hot cells found in nuclear medicine facilities.

Techniques for Loading Technetium-99m and Rhenium-186/188 Radionuclides into Preformed Liposomes for Diagnostic Imaging and Radionuclide Therapy.

PubMed

Goins, Beth; Bao, Ande; Phillips, William T

2017-01-01

Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m ( 99m Tc), for noninvasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 ( 186/188 Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load 99m Tc or 186/188 Re into preformed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport 99m Tc or 186/188 Re across the lipid bilayer of the preformed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the 99m Tc and 186/188 Re within the liposomes. In the first method, 99m Tc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and 99m Tc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, 99m Tc or 186/188 Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and 99m Tc-BMEDA or 186/188 Re-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium sulfate (pH) gradient loading technique is employed using liposomes with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for 99m Tc or 186/188 Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, 99m Tc/ 186/188 Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the 99m Tc/ 186/188 Re-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with 99m Tc-BMEDA for noninvasive monitoring of tissue distribution during treatment or with 186/188 Re-BMEDA for combination chemo-radionuclide therapy.

Detection of atherosclerotic plaques in ApoE-deficient mice using (99m)Tc-duramycin.

PubMed

Liu, Zhonglin; Larsen, Brandon T; Lerman, Lilach O; Gray, Brian D; Barber, Christy; Hedayat, Ahmad F; Zhao, Ming; Furenlid, Lars R; Pak, Koon Y; Woolfenden, James M

2016-08-01

Apoptosis of macrophages and smooth muscle cells is linked to atherosclerotic plaque destabilization. The apoptotic cascade leads to exposure of phosphatidylethanolamine (PE) on the outer leaflet of the cell membrane, thereby making apoptosis detectable using probes targeting PE. The objective of this study was to exploit capabilities of a PE-specific imaging probe, (99m)Tc-duramycin, in localizing atherosclerotic plaque and assessing plaque evolution in apolipoprotein-E knockout (ApoE(-/-)) mice. Atherosclerosis was induced in ApoE(-/-) mice by feeding an atherogenic diet. (99m)Tc-duramycin images were acquired using a small-animal SPECT imager. Six ApoE(-/-) mice at 20weeks of age (Group I) were imaged and then sacrificed for ex vivo analyses. Six additional ApoE(-/-) mice (Group II) were imaged at 20 and 40weeks of age before sacrifice. Six ApoE wild-type (ApoE(+/+)) mice (Group III) were imaged at 40weeks as controls. Five additional ApoE(-/-) mice (40weeks of age) (Group IV) were imaged with a (99m)Tc-labeled inactive peptide, (99m)Tc-LinDUR, to assess (99m)Tc-duramycin targeting specificity. Focal (99m)Tc-duramycin uptake in the ascending aorta and aortic arch was detected at 20 and 40weeks in the ApoE(-/-) mice but not in ApoE(+/+) mice. (99m)Tc-duramycin uptake in the aortic lesions increased 2.2-fold on quantitative imaging in the ApoE(-/-) mice between 20 and 40weeks. Autoradiographic and histological data indicated significantly increased (99m)Tc-duramycin uptake in the ascending aorta and aortic arch associated with advanced plaques. Quantitative autoradiography showed that the ratio of activity in the aortic arch to descending thoracic aorta, which had no plaques or radioactive uptake, was 2.1 times higher at 40weeks than at 20weeks (6.62±0.89 vs. 3.18±0.29, P<0.01). There was barely detectable focal uptake of (99m)Tc-duramycin in the aortic arch of ApoE(+/+) mice. No detectable (99m)Tc-LinDUR uptake was observed in the aortas of ApoE(-/-) mice. PE-targeting properties of (99m)Tc-duramycin in the atherosclerotic mouse aortas were noninvasively characterized. (99m)Tc-duramycin is promising in localizing advanced atherosclerotic plaques. Copyright © 2016 Elsevier Inc. All rights reserved.

Method for the production of .sup.99m Tc compositions from .sup.99 Mo-containing materials

DOEpatents

Bennett, Ralph G.; Christian, Jerry D.; Grover, S. Blaine; Petti, David A.; Terry, William K.; Yoon, Woo Y.

1998-01-01

An improved method for producing .sup.99m Tc compositions from .sup.99 Mo compounds. .sup.100 Mo metal or .sup.100 MoO.sub.3 is irradiated with photons in a particle (electron) accelerator to ultimately produce .sup.99 MoO.sub.3. This composition is then heated in a reaction chamber to form a pool of molten .sup.99 MoO.sub.3 with an optimum depth of 0.5-5 mm. A gaseous mixture thereafter evolves from the molten .sup.99 MoO.sub.3 which contains vaporized .sup.99 MoO.sub.3, vaporized .sup.99m TcO.sub.3, and vaporized .sup.99m TcO.sub.2. This mixture is then combined with an oxidizing gas (O.sub.2(g)) to generate a gaseous stream containing vaporized .sup.99m Tc.sub.2 O.sub.7 and vaporized .sup.99 MoO.sub.3. Next, the gaseous stream is cooled in a primary condensation stage in the reaction chamber to remove vaporized .sup.99 MoO.sub.3. Cooling is undertaken at a specially-controlled rate to achieve maximum separation efficiency. The gaseous stream is then cooled in a sequential secondary condensation stage to convert vaporized .sup.99m Tc.sub.2 O.sub.7 into a condensed .sup.99m Tc-containing reaction product which is collected.

Method for the production of {sup 99m}Tc compositions from {sup 99}Mo-containing materials

DOEpatents

Bennett, R.G.; Christian, J.D.; Grover, S.B.; Petti, D.A.; Terry, W.K.; Yoon, W.Y.

1998-09-01

An improved method is described for producing {sup 99m}Tc compositions from {sup 99}Mo compounds. {sup 100}Mo metal or {sup 100}MoO{sub 3} is irradiated with photons in a particle (electron) accelerator to ultimately produce {sup 99}MoO{sub 3}. This composition is then heated in a reaction chamber to form a pool of molten {sup 99}MoO{sub 3} with an optimum depth of 0.5--5 mm. A gaseous mixture thereafter evolves from the molten {sup 99}MoO{sub 3} which contains vaporized {sup 99}MoO{sub 3}, vaporized {sup 99m}TcO{sub 3}, and vaporized {sup 99m}TcO{sub 2}. This mixture is then combined with an oxidizing gas (O{sub 2(g)}) to generate a gaseous stream containing vaporized {sup 99m}Tc{sub 2}O{sub 7} and vaporized {sup 99}MoO{sub 3}. Next, the gaseous stream is cooled in a primary condensation stage in the reaction chamber to remove vaporized {sup 99}MoO{sub 3}. Cooling is undertaken at a specially-controlled rate to achieve maximum separation efficiency. The gaseous stream is then cooled in a sequential secondary condensation stage to convert vaporized {sup 99m}Tc{sub 2}O{sub 7} into a condensed {sup 99m}Tc-containing reaction product which is collected. 1 fig.

Imaging experimental intraabdominal abscesses with 99mTc-PEG liposomes and 99mTc-HYNIC IgG.

PubMed Central

Dams, E T; Reijnen, M M; Oyen, W J; Boerman, O C; Laverman, P; Storm, G; van der Meer, J W; Corstens, F H; van Goor, H

1999-01-01

OBJECTIVE: To evaluate the accuracy of technetium-99m-labeled polyethylene glycol-coated liposomes (99mTc-PEG liposomes) and technetium-99m-labeled nonspecific human immunoglobulin G (99mTc-HYNIC IgG) for the scintigraphic detection of experimental intraabdominal abscesses in comparison with that of a standard agent, gallium-67 citrate. BACKGROUND: Scintigraphic imaging techniques can be very useful for the rapid and accurate localization of intraabdominal abscesses. Two newly developed radiolabeled agents, 99mTc-PEG liposomes and 99mTc-HYNIC IgG, have shown to be excellent agents for imaging experimental focal infection, but have not yet been studied in the detection of abdominal abscesses. METHODS: Intraabdominal abscesses were induced in 42 rats using the cecal ligation and puncture technique. Seven days later, randomized groups of rats received 99mTc-PEG liposomes, 99mTc-HYNIC IgG, or 67Ga citrate intravenously. The rats were imaged up to 24 hours after the injection. The biodistribution of the radiolabel was determined by counting dissected tissues ex vivo. Macroscopic intraabdominal abnormalities and focal uptake on the images were independently scored on a semiquantitative scale. RESULTS: 99mTc-PEG liposomes provided the earliest scintigraphic visualization of the abscess (as soon as 2 hours after the injection vs. 4 hours for the other two agents). Liposomes, IgG, and gallium all showed similarly high absolute uptake in the abscess. Focal uptake of liposomes and gallium correlated best with the extent of the macroscopic abnormalities. CONCLUSIONS: 99mTc-PEG liposomes and 99mTc-HYNIC IgG performed at least as well as the standard agent, 67Ga citrate, in the detection of experimental intraabdominal abscesses, with obvious advantages such as lower radiation exposure and more favorable physical properties. Of the two technetium agents, the liposomes seemed to be superior, providing the earliest diagnostic image and the best correlation with the inflammatory abnormalities. In addition, the preferential localization of radiolabeled PEG liposomes holds promise for targeted delivery of liposome-encapsulated drugs. Images Figure 1. PMID:10203089

Comparison of 99mTc-UBI 29-41, 99mTc-Ciprofloxacin, 99mTc-Ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study.

PubMed

Auletta, Sveva; Baldoni, Daniela; Varani, Michela; Galli, Filippo; Hajar, Iman A; Duatti, Adriano; Ferro-Flores, Guillermina; Trampuz, Andrej; Signore, Alberto

2017-08-28

Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-Ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335). Stability controls were performed with the labelled radiopharmaceuticals during 6 h in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 °C and 4 °C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues. Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: 99mTc-UBI and 99mTcN-CiproCS2 showed higher infected cage/sterile cage ratio at 24 h for both E. coli and S. aureus; 99mTc-Ciprofloxacin at 24 h for both E. coli and at 4 h for S. aureus; 111In-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages. 99mTc-UBI, 99mTcN-CiproCS2 showed poor in vitro binding but good in vivo binding to E. coli only. 111In-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. 99mTc-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.

Comparison of 99mTc-HYNIC-TOC and HYNIC-TATE octreotide scintigraphy with FDG PET and 99mTc-MIBI in local recurrent or distant metastatic thyroid cancers.

PubMed

Sager, Sait; Kabasakal, Levent; Halac, Metin; Maecke, Helmut; Uslu, Lebriz; Önsel, Çetin; Kanmaz, Bedii

2013-05-01

There have been various studies for early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study is to evaluate the clinical utility of 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE, octreotide derivatives, to detect recurrences or distant metastases in 131I-negative thyroglobulin positive thyroid cancer patients and to compare the lesions with FDG PET and 99mTc-MIBI studies in the same patient group. Twenty differentiated thyroid cancer patients, 7 male and 13 female, mean age 54.6 ± 15.3 (range 13-78 years), were included in this study. Eighteen patients had papillary thyroid cancer and 2 had follicular thyroid cancer. Fifteen patients received HYNIC-TOC and 5 patients received HYNIC-TATE as a radiopharmaceutical. All patients underwent whole-body scan 1 and 4 hours after injection of octreotide derivatives and SPECT imagings were performed from the suspicious sites. The lesions that were seen in 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE studies were compared with 99mTc-MIBI and FDG-PET studies. Among 99mTc-HYNIC-TOC and 99mTc-HYNIC-TATE scintigraphies, 15 patient studies were evaluated as true positive (75%) and 5 were false negative (25%). The total number of lesions in octreotide scintigraphy was 48 in 20 patients. Of 20 patients, 19 had FDG-PET study, 15 of them were evaluated as true positive (78.9%), and 4 them were evaluated as false negative (21.1%). Total number of lesions in FDG PET was 74. 99mTc-MIBI study was positive in 11 patients (55%) and negative in 9 patients (45%). Total number of lesions in 99mTc-MIBI was 25. Technetium-labeled somatostatin receptor scintigraphy analogues HYNIC-TOC and HYNIC-TATE are useful imaging alternatives in somatostatin receptor expressing thyroid cancer patients. Radiolabeling is easy and they are readily available for routine use.

Measurement of technetium-99 in Marshall Islands soil samples by ICP-MS

PubMed

Tagami; Uchida; Hamilton; Robison

2000-07-01

Extraction techniques for recovery of technetium-99 (99Tc) for Inductively Coupled Plasma Mass Spectrometry (ICP-MS) measurements were evaluated using soil samples collected from the Marshall Islands. The results of three different extraction techniques were compared: (MI) acid leaching of Tc from ashed soil; (M2) acid leaching of Tc from raw dry soil; and (M3) Tc volatilization from ashed soil using a combustion apparatus. Total Tc recoveries varied considerably between the extraction techniques but each method yielded similar analytical results for 99Tc. Applications of these extraction techniques to a series of environmental samples and ICP-MS measurements have yielded first data on the 99Tc content of Marshall Islands soil samples contaminated with close-in radioactive fallout from nuclear weapons testing. The 99Tc activity concentration in the soil samples ranged between 0.1 and 1.1 mBq g(-1) dry weight (dw). The limit of detection for 99Tc by ICP-MS was 0.17 mBq per sample or 0.014 mBq g(-1) dw under standard operating conditions.

Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent (99m)Tc-Duramycin.

PubMed

Audi, Said; Li, Zhixin; Capacete, Joseph; Liu, Yu; Fang, Wei; Shu, Laura G; Zhao, Ming

2012-08-01

(99m)Tc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between (99m)Tc-Duramycin and the target tissue. High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague-Dawley rats. Target binding and biodistribution of (99m)Tc-duramycin were captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of (99m)Tc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of (99m)Tc-Duramycin in normal and ischemic myocardial tissue. (99m)Tc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to (99m)Tc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for (99m)Tc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9-fold reduction in binding affinity. (99m)Tc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of (99m)Tc-Duramycin as a novel PE-binding agent. Copyright © 2012 Elsevier Inc. All rights reserved.

Direct production of 99mTc using a small medical cyclotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lapi, Suzanne

This project describes an investigation towards the production of 99mTc with a small medical cyclotron. This endeavor addresses the current urgent problem of availability of 99mTc due to the ongoing production reactor failures and the upcoming Canadian reactor shut down. Currently, 99mTc is produced via nuclear fission using highly enriched uranium which is a concern due to nuclear proliferation risks. In addition to this, the United States is dependent solely on currently unreliable foreign sources of this important medical isotope. Clearly, a need exists to probe alternative production routes of 99mTc. In the first year, this project measured cross-sections andmore » production yields of potential pathways to 99mTc and associated radionuclidic impurities produced via these pathways using a small 15 MeV medical cyclotron. During the second and third years target systems for the production of 99mTc via the most promising reaction routes were developed and separation techniques for the isolation of 99mTc from the irradiated target material will be investigated. Systems for the recycling of the enriched target isotopes as well as automated target processing systems were examined in years four and five. This project has the potential to alleviate some of the current crisis in the medical community by developing a technique to produce 99mTc on location at a university hospital. This technology will be applicable at many other sites in the United States as many other similar, low energy (<20 MeV) cyclotrons (currently used for a few hours per day for the production of [ 18F]fluorodeoxyglucose) are available for production of 99mTc though this method, thus leading to job creation and preservation.« less

Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-11-01

Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g. A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions. We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.

Pixelized Measurement of (99m)Tc-HDP Micro Particles Formed in Gamma Correction Phantom Pinhole Scan: a Reference Study.

PubMed

Jung, Joo-Young; Cheon, Gi Jeong; Lee, Yun-Sang; Ha, Seunggyun; Chae, Mi-Hye; Chung, Yong-An; Yoon, Do Kyun; Bahk, Yong-Whee

2016-09-01

Currently, traumatic bone diseases are diagnosed by assessing the micro (99m)Tc-hydroxymethylene diphosphonate (HDP) uptake in injured trabeculae with ongoing osteoneogenesis demonstrated by gamma correction pinhole scan (GCPS). However, the mathematic size quantification of micro-uptake is not yet available. We designed and performed this phantom-based study to set up an in-vitro model of the mathematical calculation of micro-uptake by the pixelized measurement. The micro (99m)Tc-HDP deposits used in this study were spontaneously formed both in a large standard flood and small house-made dish phantoms. The processing was as follows: first, phantoms were flooded with distilled water and (99m)Tc-HDP was therein injected to induce micro (99m)Tc-HDP deposition; second, the deposits were scanned using parallel-hole and pinhole collimator to generally survey (99m)Tc-HDP deposition pattern; and third, the scans underwent gamma correction (GC) to discern individual deposits for size measurement. In original naïve scans, tracer distribution was simply nebulous in appearance and, hence, could not be measured. Impressively, however, GCPS could discern individual micro deposits so that they were calculated by pixelized measurement. Phantoms naturally formed micro (99m)Tc-HDP deposits that are analogous to (99m)Tc-HDP uptake on in-vivo bone scan. The smallest one we measured was 0.414 mm. Flooded phantoms and therein injected (99m)Tc-HDP form nebulous micro (99m)Tc-HDP deposits that are rendered discernible by GCPB and precisely calculable using pixelized measurement. This method can be used for precise quantitative and qualitative diagnosis of bone and joint diseases at the trabecular level.

99mTc-zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging.

PubMed

Rashed, H M; Marzook, F A; Farag, H

2016-12-01

Lung imaging radiopharmaceuticals are helpful agents for measuring pulmonary blood flow and allow detection of pulmonary embolism and lung cancer. The goal of this study was to develop a novel potential radiopharmaceutical for lung imaging. Zolmitriptan (a selective serotonin receptor agonist) was successfully labeled with 99m Tc via direct labeling method under reductive conditions studying different factors affecting the labeling efficiency. 99m Tc-zolmitriptan was obtained with a maximum labeling yield of 92.5 ± 0.61 % and in vitro stability up to 24 h. Molecular modeling was done to predict the structure of 99m Tc-zolmitriptan and ensure that radiolabeling did not affect binding ability of zolmitriptan to its receptor. Biodistribution studies showed that maximum lung uptake of 99m Tc-zolmitriptan was 23.89 ± 1.2 % injected dose/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the renal pathway. Scintigraphic images confirmed the biodistribution results showing a high resolution lung image with low accumulation of radioactivity in other organs except kidneys and urinary bladder. 99m Tc-zolmitriptan is not a blood product and so it is more safe than the currently available 99m Tc-MAA, and its lung uptake is higher than that of the recently discovered 123 I-IPMPD, 99m Tc(CO) 5 I and 99m Tc-DHPM. So, 99m Tc-zolmitriptan could be used as a hopeful radiopharmaceutical for lung scintigraphic imaging.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H.B.; Blaufox, M.D.

Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using /sup 99m/Tc mercaptoacetyltriglycine ((/sup 99m/Tc)MAG-3) and /sup 131/I orthoiodohippurate ((/sup 131/I)OIH). Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH in normals didn't change significantly after Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ((/sup 99m/Tc)MAG-3 p less than 0.01 and (/sup 131/I)OIH pmore » less than 0.025) and clamped kidney clearance decreased after inhibition ((/sup 99m/Tc)MAG-3, p less than 0.01, (/sup 131/I)OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ((/sup 99m/Tc)MAG-3 p less than 0.0025 and (/sup 131/I)OIH, p less than 0.001). The ratio of (/sup 99m/Tc)MAG-3 to (/sup 131/I)OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels (/sup 131/I)orthoiodohippurate in renovascular hypertension.« less

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Levitsky, Lynne L

2015-01-01

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

Dose calibrator linearity test: 99mTc versus 18F radioisotopes*

PubMed Central

Willegaignon, José; Sapienza, Marcelo Tatit; Coura-Filho, George Barberio; Garcez, Alexandre Teles; Alves, Carlos Eduardo Gonzalez Ribeiro; Cardona, Marissa Anabel Rivera; Gutterres, Ricardo Fraga; Buchpiguel, Carlos Alberto

2015-01-01

Objective The present study was aimed at evaluating the viability of replacing 18F with 99mTc in dose calibrator linearity testing. Materials and Methods The test was performed with sources of 99mTc (62 GBq) and 18F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical 99mTc and 18F sources activities were calculated and subsequently compared. Results Mean deviations between experimental and theoretical 99mTc and 18F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the 99mTc source as measured with the equipment pre-calibrated to measure 99mTc and 18F was 3.42 (± 0.06), and for the 18F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time. Conclusion The results of the linearity test using 99mTc were compatible with those obtained with the 18F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in 18F acquisition suggest 99mTc as the element of choice to perform dose calibrator linearity tests in centers that use 18F, without any detriment to the procedure as well as to the quality of the nuclear medicine service. PMID:25798005

Design and performance of an automated radionuclide separator: its application on the determination of ⁹⁹Tc in groundwater.

PubMed

Chung, Kun Ho; Choi, Sang Do; Choi, Geun Sik; Kang, Mun Ja

2013-11-01

A modular automated radionuclide separator for (99)Tc (MARS Tc-99) has been developed for the rapid and reproducible separation of technetium in groundwater samples. The control software of MARS Tc-99 was developed in the LabView programming language. An automated radiochemical method for separating (99)Tc was developed and validated by the purification of (99m)Tc tracer solution eluted from a commercial (99)Mo/(99m)Tc generator. The chemical recovery and analytical time for this radiochemical method were found to be 96 ± 2% and 81 min, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced (99m)Tc yields.

PubMed

Tanguay, J; Hou, X; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-05-21

Cyclotron production of (99m)Tc through the (100)Mo(p,2n) (99m)Tc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional (99m)Tc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity (99m)Tc. However, variations in proton beam currents and the thickness and isotopic composition of enriched (100)Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute (99m)Tc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including (100)Mo target thicknesses and proton beam currents, and reproducibility of absolute (99m)Tc yields (defined as the end of bombardment (EOB) (99m)Tc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB (99m)Tc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in (99m)Tc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of (99m)Tc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced (99m)Tc.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced 99mTc yields

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-05-01

Cyclotron production of 99mTc through the 100Mo(p,2n) 99mTc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional 99mTc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity 99mTc. However, variations in proton beam currents and the thickness and isotopic composition of enriched 100Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute 99mTc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including 100Mo target thicknesses and proton beam currents, and reproducibility of absolute 99mTc yields (defined as the end of bombardment (EOB) 99mTc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB 99mTc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in 99mTc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of 99mTc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced 99mTc.

Amyloidosis of heart and liver: comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate for detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, V.W.; Caldarone, A.G.; Falk, R.H.

1983-07-01

A prospective, comparative study was made of the efficacy of technetium-99m pyrophosphate (Tc PYP) and technetium-99m methylene diphosphonate (Tc MDP) in detecting soft-tissue amyloidois. Tc PYP and Tc MDP scans were obtained within ten-day intervals in seven patients with histologically proven amyloidosis. Tc PYP was a better scanning agent for soft-tissue amyloidosis in all patients. Cardiac and hepatic involvement were proved by autopsy in one patient. Involvement of the heart was confirmed by echocardiography in five patients. The potential use of tc PYP scannning as a screening test for soft-tissue amyloidosis is discussed.

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

PubMed

Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

Transglutaminase-mediated conjugation and nitride-technetium-99m labelling of a bis(thiosemicarbazone) bifunctional chelator.

PubMed

Salvarese, Nicola; Spolaore, Barbara; Marangoni, Selena; Pasin, Anna; Galenda, Alessandro; Tamburini, Sergio; Cicoria, Gianfranco; Refosco, Fiorenzo; Bolzati, Cristina

2018-06-01

An assessment study involving the use of the transglutaminase (TGase) conjugation method and the nitride-technetium-99m labelling on a bis(thiosemicarbazone) (BTS) bifunctional chelating agent is presented. The previously described chelator diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-(N 4 -amino-3-thiosemicarbazone), H 2 ATSM/A, has been functionalized with 6-aminohexanoic acid (ε-Ahx) to generate the bifunctional chelating agent diacetyl-2-(N 4 -methyl-3-thiosemicarbazone)-3-[N 4 -(amino)-(6-aminohexanoic acid)-3-thiosemicarbazone], H 2 ATSM/A-ε-Ahx (1), suitable for conjugation to glutamine (Gln) residues of bioactive molecules via TGase. The feasibility of the TGase reaction in the synthesis of a bioconjugate derivative was investigated using Substance P (SP) as model peptide. Compounds 1 and H 2 ATSM/A-ε-Ahx-SP (2) were labelled with nitride-technetium-99m, obtaining the complexes [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx)] ( 99m Tc1) and [ 99m Tc][Tc(N)(ATSM/A-ε-Ahx-SP)] ( 99m Tc2). The chemical identity of 99m Tc1 and 99m Tc2 was confirmed by radio/UV-RP-HPLC combined with ESI-MS analysis on the respective carrier-added products 99g/99m Tc1 and 99g/99m Tc2. The stability of the radiolabelled complexes after incubation in various environments was investigated. All the results were compared with those obtained for the corresponding 64 Cu-analogues, 64 Cu1 and 64 Cu2. The TGase reaction allows the conjugation of 1 with the peptide, but it is not highly efficient due to instability of the chelator in the required conditions. The SP-conjugated complexes are unstable in mouse and human sera. However, indeed the BTS system can be exploited as nitride-technetium-99m chelator for highly efficient technetium labelling, thus making compound 1 worthy of further investigations for new targeted technetium and copper radiopharmaceuticals encompassing Single Photon Emission Computed Tomography and Positron Emission Tomography imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Tc-99m imaging in thyroidectomized differentiated thyroid cancer patients immediately before I-131 treatment.

PubMed

Tsai, Chi-Jung; Cheng, Cheng-Yi; Shen, Daniel Hueng-Yuan; Kuo, Shou Jen; Wang, Lien-Yen; Lee, Chiang-Hsuan; Wang, Jhi-Joung; Chang, Ming-Che; Huang, Wen-Sheng

2016-02-01

The aim of this study was to evaluate the clinical role of technetium-99m pertechnetate (Tc-99m) imaging in thyroidectomized differentiated thyroid cancer patients immediately before radioiodine-131 (I-131) treatment (Tx). Eighty-six consecutive post-total-thyroidectomy patients (15 men, 71 women; mean age: 46.8 years) with pathologically diagnosed differentiated thyroid cancer were retrospectively studied. Tc-99m imaging immediately before I-131 Tx using both patient-based and lesion-based measurements were analyzed and were further compared with those of post-Tx I-131 whole-body scans. For patients with unequivocally positive Tc-99m uptake, the sensitivity was 77% (patient-based) and 59% (site-based). The positive predictive value (PPV) was 100% for both patient-based and site-based measurements. If equivocal Tc-99m uptake was counted as positive, the sensitivity was 83 and 67%, and the PPV was 100 and 99% for patient-based and site-based measurements, respectively. (a) To increase sensitivity yet maintaining high PPV, equivocal Tc-99m uptake should be considered a positive finding. (b) The nearly 100% PPV of Tc-99m imaging immediately before I-131 Tx for remnant detection suggests that Tc-99m imaging not only serves as an alternative to low-dose I-131 scanning in the low-risk post-thyroidectomy patients but also provides a clue for the subsequent I-131 therapeutic dosage and even for the outcome prediction.

Streptozotocin (STZ) and schistosomiasis mansoni change the biodistribution of radiopharmaceutical sodium (99m)Tc-pertechnetate in mice.

PubMed

Góes, Vanessa Coelho; Neves, Renata Heisler; Arnóbio, Adriano; Bernardo-Filho, Mario; Machado-Silva, José Roberto

2016-09-01

Technetium-99m ((99m)Tc) is a radionuclide commonly used in nuclear medicine to obtain (99m)Tc-radiopharmaceuticals, which can be used to evaluate either physiological processes or changes related to diseases. It is also used in some experimental studies. Streptozotocin (STZ) administration to rodents causes lesions in very early stages and induces severe and permanent diabetes. Most morbidity of schistosomiasis mansoni is attributed to a granulomatous inflammatory response and associated liver fibrosis. This study was designed to investigate whether STZ administration and schistosomiasis modify the biodistribution of the radiopharmaceutical sodium (99m)Tc-pertechnetate. Adult female mice were infected by exposure to 100Schistosoma mansoni cercariae (BH strain, Belo Horizonte, Brazil) and euthanized after nine weeks. STZ was administered by a single intraperitoneal injection of 100mg/kg body weight, 3 or 15days before euthanasia. Each animal received 100μl of sodium (Na) (99m)Tc-pertechnetate ((99m)TcO4(-)) (740kBq). The animals were divided into four groups: A, uninfected; B, infected; C, uninfected + STZ; and D, infected + STZ. Blood, brain, thyroid, heart, lungs, liver, spleen, pancreas and kidneys were removed. The radioactivity was counted and the percentage of the injected dose of Na(99m)TcO4 per gram of the organ (% ID/g) was determined. Three days after the STZ injection, there was a decrease of Na(99m)TcO4 uptake by the liver, lungs, pancreas and kidneys (p<0.05) in group D when compared with group A. After 15days, the decrease of Na(99m)TcO4 uptake occurred also in the brain, thyroid, heart, spleen and blood (p<0.05) in group D. We demonstrated modifications on the biodistribution of Na(99m)TcO4 due to STZ administration and schistosomiasis, possibly due to physiological alterations in some organs. The biodistribution of radiopharmaceutical Na(99m)TcO4 should be carefully evaluated in subjects with diabetes and/or schistosomiasis infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Preparation and evaluation of effect on Escherichia coli and Staphylococcus aureus of radiolabeled ampicillin-loaded graphene oxide nanoflakes.

PubMed

Yurt, Fatma; Ersöz, Onur Alp; Harputlu, Ersan; Ocakoglu, Kasim

2018-06-01

Ampicillin is a one of effective antibiotics against Gram-positive and Gram-negative bacteria. This study aimed to label ampicillin-loaded graphene oxide nanoflake (AMP-GO) with 99m Tc and evaluate of its in vitro binding to Staphylococcus aureus and Escherichia coli. Firstly, ampicillin was loaded into graphene oxide nanoflake prepared. AMP-GO was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) techniques, and the amount of loaded ampicillin onto GO was determined by UV-Vis absorption spectroscopy. AMP and AMP-GO were labeled with 99m Tc using stannous chloride reducing agent. Labeling efficiency of 99m Tc-AMP-GO was found to be 97.66 ± 2.06%. 99m Tc-AMP-GO has higher binding efficiencies to both S. aureus and E. coli than 99m Tc-AMP. 99m Tc-AMP-GO could be promising candidate as agent infection nuclear imaging. Furthermore, in vivo studies of 99m Tc-AMP-GO with infected rats are planned to be performed. © 2018 John Wiley & Sons A/S.

Evaluating 99mTc Auger electrons for targeted tumor radiotherapy by computational methods.

PubMed

Tavares, Adriana Alexandre S; Tavares, João Manuel R S

2010-07-01

Technetium-99m (99mTc) has been widely used as an imaging agent but only recently has been considered for therapeutic applications. This study aims to analyze the potential use of 99mTc Auger electrons for targeted tumor radiotherapy by evaluating the DNA damage and its probability of correct repair and by studying the cellular kinetics, following 99mTc Auger electron irradiation in comparison to iodine-131 (131I) beta minus particles and astatine-211 (211At) alpha particle irradiation. Computational models were used to estimate the yield of DNA damage (fast Monte Carlo damage algorithm), the probability of correct repair (Monte Carlo excision repair algorithm), and cell kinetic effects (virtual cell radiobiology algorithm) after irradiation with the selected particles. The results obtained with the algorithms used suggested that 99mTc CKMMX (all M-shell Coster-Kroning--CK--and super-CK transitions) electrons and Auger MXY (all M-shell Auger transitions) have a therapeutic potential comparable to high linear energy transfer 211At alpha particles and higher than 131I beta minus particles. All the other 99mTc electrons had a therapeutic potential similar to 131I beta minus particles. 99mTc CKMMX electrons and Auger MXY presented a higher probability to induce apoptosis than 131I beta minus particles and a probability similar to 211At alpha particles. Based on the results here, 99mTc CKMMX electrons and Auger MXY are useful electrons for targeted tumor radiotherapy.

Effect of metabolic alterations on the accumulation of technetium-99m-labeled d, l-HMPAO in slices of rat cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, C.S.; Tow, D.E.; Yu, C.C.

1994-03-01

It is widely recognized that the distribution of technetium-99m-labeled d,l-hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) in the brain is determined by the regional blood flow. However, other factors may affect this process including the metabolism of the brain tissue. To examine this possibility we studied the effects of metabolic alterations on {sup 99m}Tc-HMPAO uptake in rat brain cortex slices, with concurrent measurement of oxygen consumption (QO{sub 2}). {sup 99m}Tc-HMPAO uptake was determined by incubating slices of rat cerebral cortex at 37{degrees}C in Krebs-Ringer phosphate glucose medium containing {sup 99m}Tc-HMPAO with and without test substances. Differential gradients for {sup 99m}Tc activity betweenmore » the tissue and the suspending medium (T/M ratio) were derived from the equation T/M[{sup 99m}Tc] = counts per gram of tissue/counts per milliliter of medium. The QO{sub 2} of the brain slices was measured using a biological oxygen monitor equipped with a polarographic oxygen probe. Inhibitors affecting oxidative phosphorylation caused parallel suppression of the T/M ratio and QO{sub 2}. Agents that uncouple oxidation from phosphorylation increased the QO{sub 2} and decreased the T/M ratio. Incubation of slices at 22{degrees}C depressed the T/M ratio and QO{sub 2}. The presence of inhibitors of oxidative phosphorylation in the incubation medium increased the release of {sup 99m}Tc activity from slices that had been prelabeled with {sup 99m}Tc-HMPAO. These findings suggest that the altered metabolic status of the brain tissue modulates the kinetics and net accumulation of {sup 99m}Tc-HMPAO at the cellular level by either depressing uptake, increasing back-diffusion, or both. 33 refs., 4 figs., 3 tabs.« less

(99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

PubMed

Taylor, Andrew T; Lipowska, Malgorzata; Marzilli, Luigi G

2010-03-01

Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.

A solvent-extraction module for cyclotron production of high-purity technetium-99m.

PubMed

Martini, Petra; Boschi, Alessandra; Cicoria, Gianfranco; Uccelli, Licia; Pasquali, Micòl; Duatti, Adriano; Pupillo, Gaia; Marengo, Mario; Loriggiola, Massimo; Esposito, Juan

2016-12-01

The design and fabrication of a fully-automated, remotely controlled module for the extraction and purification of technetium-99m (Tc-99m), produced by proton bombardment of enriched Mo-100 molybdenum metallic targets in a low-energy medical cyclotron, is here described. After dissolution of the irradiated solid target in hydrogen peroxide, Tc-99m was obtained under the chemical form of 99m TcO 4 - , in high radionuclidic and radiochemical purity, by solvent extraction with methyl ethyl ketone (MEK). The extraction process was accomplished inside a glass column-shaped vial especially designed to allow for an easy automation of the whole procedure. Recovery yields were always >90% of the loaded activity. The final pertechnetate saline solution Na 99m TcO 4 , purified using the automated module here described, is within the Pharmacopoeia quality control parameters and is therefore a valid alternative to generator-produced 99m Tc. The resulting automated module is cost-effective and easily replicable for in-house production of high-purity Tc-99m by cyclotrons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Introduction of an 8-aminooctanoic acid linker enhances uptake of 99mTc-labeled lactam bridge-cyclized α-MSH peptide in melanoma.

PubMed

Guo, Haixun; Miao, Yubin

2014-12-01

The purpose of this study was to examine the effects of amino acid, hydrocarbon, and polyethylene glycol (PEG) linkers on the melanoma targeting and imaging properties of (99m)Tc-labeled lactam bridge-cyclized HYNIC-linker-Nle-CycMSHhex (hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2) peptides. Four novel peptides (HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex) were designed and synthesized. The melanocortin-1 receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of (99m)Tc(ethylenediaminediacetic acid [EDDA])-HYNIC-GGGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-GSGNle-CycMSHhex, (99m)Tc(EDDA)-HYNIC-PEG2Nle-CycMSHhex, and (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h after injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were further examined because of its high melanoma uptake. The inhibitory concentrations of 50% (IC50) for HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex were 0.7 ± 0.1, 0.8 ± 0.09, 0.4 ± 0.08, and 0.3 ± 0.06 nM, respectively, in B16/F1 melanoma cells. Among these four (99m)Tc-labeled peptides, (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex displayed the highest melanoma uptake (22.3 ± 1.72 percentage injected dose/g) at 2 h after injection. (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited high tumor-to-normal-organ uptake ratios except for the kidneys. The tumor-to-kidney uptake ratios of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex were 3.29, 3.63, and 6.78 at 2, 4, and 24 h, respectively, after injection. The melanoma lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2 h after injection. High melanoma uptake and fast urinary clearance of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Introduction of an 8-Aminooctanoic Acid Linker Enhances the melanoma uptake of Tc-99m-labeled Lactam Bridge-Cyclized Alpha-MSH Peptide

PubMed Central

Guo, Haixun; Miao, Yubin

2015-01-01

The purpose of this study was to examine the effects of amino acid, hydrocarbon and polyethylene glycol (PEG) linkers on melanoma targeting and imaging properties of 99mTc-labeled lactam bridge-cyclized HYNIC-linker-Nle-CycMSHhex {hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} peptides. Methods four novel peptides {HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex and HYNIC-AocNle-CycMSHhex} were designed and synthesized. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of 99mTc(EDDA)-HYNIC-GGGNle-CycMSHhex, 99mTc(EDDA)-HYNIC-GSGNle-CycMSHhex, 99mTc(EDDA)-HYNIC-PEG2Nle-CycMSHhex and 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were determined in B16/F1 melanoma-bearing C57 mice at 2 h post-injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were further examined because of its high melanoma uptake. Results The IC50 values of HYNIC-GGGNle-CycMSHhex, HYNIC-GSGNle-CycMSHhex, HYNIC-PEG2Nle-CycMSHhex, and HYNIC-AocNle-CycMSHhex were 0.7 ± 0.1, 0.8 ± 0.09, 0.4 ± 0.08, and 0.3 ± 0.06 nM in B16/F1 melanoma cells, respectively. Among these four 99mTc-labeled peptides, 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex displayed the highest melanoma uptake (22.3 ± 1.72% ID/g) at 2 h post-injection. 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited high tumor to normal organ uptake ratios except for the kidneys. The tumor/kidney uptake ratios of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex were 3.29, 3.63 and 6.78 at 2, 4 and 24 h post-injection. The melanoma lesions were clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2 h post-injection. Conclusion High melanoma uptake and fast urinary clearance of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex highlighted its potential for metastatic melanoma detection in the future. PMID:25453052

Preoperative localization of parathyroid carcinoma using Tc-99m MIBI.

PubMed

Kitapçi, M T; Tastekin, G; Turgut, M; Caner, B; Kars, A; Barista, I; Bekdik, C

1993-03-01

A patient with parathyroid cancer is presented who underwent Tc-99m MIBI scintigraphy. The Tc-99m MIBI image demonstrated increased accumulation of activity at the lower pole of the left thyroid lobe which was later confirmed as a parathyroid cancer. Uptake by parathyroid cancer must be kept in mind as a cause of increased Tc-99m MIBI accumulation when a disease is in question in the thyroid or parathyroid gland.

A novel Tc-99 m and fluorescence labeled peptide as a multimodal imaging agent for targeting angiogenesis in a murine tumor model.

PubMed

Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Seul-Gi; Kim, Dae-Weung

2016-11-01

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin α V β 3 . In the present study, we successfully developed a TAMRA-GHEG-ECG-SDV peptide labeled with both Tc-99 m and TAMRA to target the integrin α V β 3 of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99 m TAMRA-GHEG-ECG-SDV as a dual-modality imaging agent for tumor of the murine model. TAMRA-GHEG-ECG-SDV was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-SDV with Tc-99 m was done using ligand exchange methods. Labeling stability and cytotoxicity studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed in murine models with HT-1080 and HT-29 tumors. A tumor tissue slide was prepared and analyzed using confocal microscopy. After radiolabeling procedures with Tc-99 m, the Tc-99 m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). In the gamma camera imaging study, a substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin α V β 3 positive) and low uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-29 tumor (integrin α V β 3 negative) were demonstrated. A competition study revealed that HT-1080 tumor uptake was effectively blocked by the co-injection of an excess concentration of SDV. Specific uptake of Tc-99 m TAMRA-GHEG-ECG-SDV was confirmed by biodistribution, ex vivo imaging and confocal microscopy studies. Our in vivo and in vitro studies revealed substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV in the integrin α V β 3 -positive tumor. Tc-99 m TAMRA-GHEG-ECG-SDV could be a good candidate for a dual-modality imaging agent targeting tumor angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-Microspheres Used in Preradioembolization Dosimetry: Influence on the Liver-Lung Shunt.

PubMed

Grosser, Oliver S; Ruf, Juri; Kupitz, Dennis; Pethe, Annette; Ulrich, Gerhard; Genseke, Philipp; Mohnike, Konrad; Pech, Maciej; Richter, Wolf S; Ricke, Jens; Amthauer, Holger

2016-06-01

Perfusion scintigraphy using (99m)Tc-labeled albumin aggregates is mandatory before hepatic radioembolization with (90)Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, (99m)Tc-MAA (macroaggregated serum albumin [MAA]) and (99m)Tc-HSA (human serum albumin [HSA]), was assessed. In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver-lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Compared with (99m)Tc-MAA-microspheres, (99m)Tc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Liver perfusion imaging in patients with primary and metastatic liver malignancy: prospective comparison between 99mTc-MAA spect and dynamic CT perfusion.

PubMed

Reiner, Caecilia S; Goetti, Robert; Burger, Irene A; Fischer, Michael A; Frauenfelder, Thomas; Knuth, Alexander; Pfammatter, Thomas; Schaefer, Niklaus; Alkadhi, Hatem

2012-05-01

To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32-78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99m)Tc-MAA SPECT after intraarterial injection of 180 MBq 99mTc-MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P < .01) and 99mTc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862). This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Imaging of glutathione localization in brain with technetium-99M meso-hexamethyl propyleneamine oxime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasaki, T.; Toyama, H.; Oda, K.

1995-05-01

Previous studies have shown decreasing [Tc-99m] meso-HM-PAO uptake in accordance with glutathione (GSH) content in diethyl, maleate (DEM) treated mice brain. In order to elucidate the retention mechanism of [Tc-99m] HM-PAO in brain and to visualize the regional localization of GSH in the brain with [Tc-99m] meso-HM-PAO, the relationship between the tissue GSH content and uptake of [Tc-99m] meso-HM-PAO was studied in rats and rabbits. Increasing pre-load of DEM (550 mg/kg body weight), an agent to reduce GSH content by glutathione transferase, led to a decrease in GSH (control 1.972{plus_minus}0.017 vs DEM 1.138{plus_minus}0.106 mM) and uptake of [Tc-99m] meso-HM-PAO tomore » half of the control in the rat brain (control 0.281{plus_minus}0.024 vs DEM 0.153 {plus_minus} 0.009 % dose/g). On the other hand, the DEM did not decrease GSH or the uptake of [Tc-99m] meso-HM-PAO in the rabbit brain, in which glutathione transferase activity is very low. These results were also demonstrated by images with pin-hole collimated gamma camera. The uptake of [Tc-99m] meso showed variations in the regional distribution, but the d,l-isomer was uniform. [Tc-99m] meso-HM-PAO uptake was well correlated with GSH content in mice brain regions (r=0.800, p<0.02), whereas [Tc-99m]d,l-HM-PAO was not (r=0.017, p>0.5). Both [Tc-99m] mesa HM-PAO uptake and GSH content were especially high at cerebellum (Uptake: 2.598{plus_minus}0.256 % dose/g. GSH: 2.372{plus_minus}0.107 mM) as compared to other areas (Uptake;cerebral cortex 1.797{plus_minus}0.100 brain stem 1.607 {plus_minus}0.112 % dose/g. GSH: cerebral cortex 1.635{plus_minus}0.142 brain stem 1.478{plus_minus}0.141 mM).« less

Benchmark experiment for the cross section of the 100Mo(p,2n)99mTc and 100Mo(p,pn)99Mo reactions

NASA Astrophysics Data System (ADS)

Takács, S.; Ditrói, F.; Aikawa, M.; Haba, H.; Otuka, N.

2016-05-01

As nuclear medicine community has shown an increasing interest in accelerator produced 99mTc radionuclide, the possible alternative direct production routes for producing 99mTc were investigated intensively. One of these accelerator production routes is based on the 100Mo(p,2n)99mTc reaction. The cross section of this nuclear reaction was studied by several laboratories earlier but the available data-sets are not in good agreement. For large scale accelerator production of 99mTc based on the 100Mo(p,2n)99mTc reaction, a well-defined excitation function is required to optimise the production process effectively. One of our recent publications pointed out that most of the available experimental excitation functions for the 100Mo(p,2n)99mTc reaction have the same general shape while their amplitudes are different. To confirm the proper amplitude of the excitation function, results of three independent experiments were presented (Takács et al., 2015). In this work we present results of a thick target count rate measurement of the Eγ = 140.5 keV gamma-line from molybdenum irradiated by Ep = 17.9 MeV proton beam, as an integral benchmark experiment, to prove the cross section data reported for the 100Mo(p,2n)99mTc and 100Mo(p,pn)99Mo reactions in Takács et al. (2015).

Techniques for loading technetium-99m and rhenium-186/188 radionuclides into pre-formed liposomes for diagnostic imaging and radionuclide therapy.

PubMed

Goins, Beth; Bao, Ande; Phillips, William T

2010-01-01

Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m ((99m)Tc), for non-invasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 ((186/188)Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load (99m)Tc or (186/188)Re into pre-formed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport (99m)Tc or (186/188)Re across the lipid bilayer of the pre-formed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the (99m)Tc and (186/188)Re within the liposomes. In the first method, (99m)Tc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and (99m)Tc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, (99m)Tc or (186/188)Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and (99m)Tc-BMEDA or (186/188)Re-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium sulfate (pH) gradient loading technique is employed using liposomes with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for (99m)Tc or (186/188)Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, (99m)Tc/(186/188)Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the (99m)Tc/(186/188)Re-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with (99m)Tc-BMEDA for non-invasive monitoring of tissue distribution during treatment or with (186/188)Re-BMEDA for combination chemo-radionuclide therapy.

Initial Evaluation of (99m)Tc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers.

PubMed

Lipowska, Malgorzata; Klenc, Jeffrey; Folks, Russell D; Taylor, Andrew T

2014-09-01

Preclinical studies in rats showed that two of (99m)Tc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of (131)I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of (99m)Tc(CO)3(ASMA) isomers in healthy human subjects. Three ASMA ligands (rac-, L- and D-ASMA) were labeled with (99m)Tc(CO)3 using an IsoLink kit (Covidien), and each formed (99m)Tc(CO)3(ASMA) tracer was co-injected with (131)I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC. Image quality was excellent with all three agents. Each (99m)Tc(CO)3(ASMA) preparation was excreted unchanged in the urine. The plasma clearance ratio ((99m)Tc(CO)3(ASMA)/(131)I-OIH) was 81 ± 3 % for D-ASMA compared to only 20 ± 4 % for L-ASMA and 37 ± 7 % for rac-ASMA; the 81 % clearance ratio for D-ASMA isomer is still ∼ 30 % higher than the (99m)Tc-MAG3/(131)I-OIH clearance ratio (∼50-60 %). Red cell uptake was similar for all three tracers (6-9 %), and all tracers had a relatively rapid renal excretion; at 3 h, the (99m)Tc(CO)3(ASMA)/(131)I-OIH urine ratio was 100 ± 3 % for D-ASMA, 80 ± 2 % for L-ASMA and 88 ± 1 % for rac-ASMA. The renal excretion characteristics of (99m)Tc(CO)3(D-ASMA) in humans are superior to those of the other two (99m)Tc(CO)3(ASMA) isomers studied, but are still inferior to (131)I-OIH, even though there was no difference in the clearance of two of (99m)Tc(CO)3(ASMA) isomers and (131)I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of (99m)Tc(CO)3(ASMA) isomers to their subtle structural differences.

An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Donnemiller, Eveline; Ulmer, Hanno; Watfah Rychlinski, Christine; Mather, Stephen J; Moncayo, Roy

2003-05-01

The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor-to-normal tissue ratios than (111)In-OCT. This study revealed a higher sensitivity of (99m)Tc-TOC as compared with (111)In-OCT as an imaging agent for the localization of SSTR-expressing tumors. To avoid false-positive findings with (99m)Tc-OCT due to nonspecific tracer accumulation, additional scanning at 1-2 h after injection should be done.

Vertical distributions of (99)Tc and the (99)Tc/(137)Cs activity ratio in the coastal water off Aomori, Japan.

PubMed

Nakanishi, Takahiro; Zheng, Jian; Aono, Tatsuo; Yamada, Masatoshi; Kusakabe, Masashi

2011-08-01

Using a sector-field ICP-MS the vertical distributions of the (99)Tc concentration and (99)Tc/(137)Cs activity ratio were measured in the coastal waters off Aomori Prefecture, Japan, where a spent-nuclear-fuel reprocessing plant has begun test operation. The (99)Tc concentrations in surface water ranged from 1.8 to 2.4 mBq/m(3), no greater than the estimated background level. Relatively high (99)Tc/(137)Cs activity ratios (10-12 × 10(-4)) would be caused by the inflow of the high-(99)Tc/(137)Cs water mass from the Japan Sea. There is no observable contamination from the reprocessing plant in the investigated area. The (99)Tc concentration and the (99)Tc/(137)Cs activity ratio in water column showed gradual decreases with depth. Our results implied that (99)Tc behaves in a more conservative manner than (137)Cs in marine environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-02-01

Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.

PubMed

Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn

2016-03-01

Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc-99m ECG-HGK for tumor imaging. Copyright © 2016 John Wiley & Sons, Ltd.

Utility of ⁹⁹mTc-human serum albumin diethylenetriamine pentaacetic acid SPECT for evaluating endoleak after endovascular abdominal aortic aneurysm repair.

PubMed

Nakai, Motoki; Sato, Hirotatsu; Sato, Morio; Ikoma, Akira; Sonomura, Tetsuo; Nishimura, Yoshiharu; Okamura, Yoshitaka

2015-01-01

The purpose of this study was to assess the utility of (99m)Tc-human serum albumin diethylenetriamine pentaacetic acid ((99m)Tc-HSAD) SPECT in the detection of endoleaks after endovascular abdominal aortic aneurysm repair. Fifteen patients (11 men, four women) with aneurysm sac expansion of 5 mm or greater after endovascular abdominal aortic aneurysm repair underwent three-phase CT, (99m)Tc-HSAD SPECT, and CT during aortography. Sensitivity calculations for three-phase CT and (99m)Tc-HSAD SPECT were performed with CT during aortography as the reference standard. The volume of each endoleak was measured with CT during aortography. Seven subjects underwent embolization with N-butyl cyanoacrylate (NBCA)-Lipiodol (ethiodized oil, Guerbet and metallic coils. Three-phase CT and (99m)Tc-HSAD SPECT were repeated after embolization to assess their efficacy. Endoleaks were interpreted as perigraft radioisotope accumulation in 12 patients (80.0%) on (99m)Tc-HSAD SPECT images, in 13 patients (86.7%) on three-phase CT images, and in 15 patients (100%) on CT during aortography. The mean endoleak volume visualized with (99m)Tc-HSAD SPECT was 8.37 cm(3) (range, 5.2-15.1 cm(3)), and the volume not visualized was 3.47 cm(3) (2.5-4.6 cm(3)), a statistically significant difference (p = 0.019). In two patients, (99m)Tc-HSAD SPECT depicted endoleaks evident at delayed phase CT during aortography but not at three-phase CT, suggesting they were slow-filling endoleaks. Accumulation of (99m)Tc-HSAD corresponding to endoleaks disappeared after embolization, but CT evaluation of embolization was impeded by artifacts of NBCA-Lipiodol and metallic coils. Technetium-99m-labeled HSAD SPECT proved less sensitive than three-phase CT but depicted endoleaks with volumes 5.2 cm(3) or greater as perigraft radioisotope accumulation. Slow-filling endoleaks can be visualized with (99m)Tc-HSAD SPECT, which can be used to evaluate the efficacy of embolization.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prior, P; Timmins, R; Wells, R G

Dual isotope SPECT allows simultaneous measurement of two different tracers in vivo. With In111 (emission energies of 171keV and 245keV) and Tc99m (140keV), quantification of Tc99m is degraded by cross talk from the In111 photons that scatter and are detected at an energy corresponding to Tc99m. TEW uses counts recorded in two narrow windows surrounding the Tc99m primary window to estimate scatter. Iterative TEW corrects for the bias introduced into the TEW estimate resulting from un-scattered counts detected in the scatter windows. The contamination in the scatter windows is iteratively estimated and subtracted as a fraction of the scatter-corrected primarymore » window counts. The iterative TEW approach was validated with a small-animal SPECT/CT camera using a 2.5mL plastic container holding thoroughly mixed Tc99m/In111 activity fractions of 0.15, 0.28, 0.52, 0.99, 2.47 and 6.90. Dose calibrator measurements were the gold standard. Uncorrected for scatter, the Tc99m activity was over-estimated by as much as 80%. Unmodified TEW underestimated the Tc99m activity by 13%. With iterative TEW corrections applied in projection space, the Tc99m activity was estimated within 5% of truth across all activity fractions above 0.15. This is an improvement over the non-iterative TEW, which could not sufficiently correct for scatter in the 0.15 and 0.28 phantoms.« less

Imaging discordance between hepatic angiography versus Tc-99m-MAA SPECT/CT: a case series, technical discussion and clinical implications.

PubMed

Kao, Yung Hsiang; Tan, Eik Hock; Teo, Terence Kiat Beng; Ng, Chee Eng; Goh, Soon Whatt

2011-11-01

During pre-therapy evaluation for yttrium-90 (Y-90) radioembolization, it is uncommon to find severe imaging discordance between hepatic angiography versus technetium-99m-macroaggregated albumin (Tc-99m-MAA) single photon emission computed tomography with integrated low-dose CT (SPECT/CT). The reasons for severe imaging discordance are unclear, and literature is scarce. We describe 3 patients with severe imaging discordance, whereby tumor angiographic contrast hypervascularity was markedly mismatched to the corresponding Tc-99m-MAA SPECT/CT, and its clinical impact. The incidence of severe imaging discordance at our institution was 4% (3 of 74 cases). We postulate that imaging discordance could be due to a combination of 3 factors: (1) different injection rates between soluble contrast molecules versus Tc-99m-MAA; (2) different arterial flow hemodynamics between soluble contrast molecules versus Tc-99m-MAA; (3) eccentric release position of Tc-99m-MAA due to microcatheter tip location, inadvertently selecting non-target microparticle trajectories. Tc-99m-MAA SPECT/CT more accurately represents hepatic microparticle biodistribution than soluble contrast hepatic angiography and should be a key criterion in patient selection for Y-90 radioembolization. Tc-99m-MAA SPECT/CT provides more information than planar scintigraphy to guide radiation planning and clinical decision making. Severe imaging discordance at pre-therapy evaluation is ominous and should be followed up by changes to the final vascular approach during Y-90 radioembolization.

Targeted imaging of gastrin-releasing peptide receptors with 99mTc-EDDA/HYNIC-[Lys3]-bombesin: biokinetics and dosimetry in women.

PubMed

Santos-Cuevas, Clara L; Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Pichardo-Romero, Pablo A

2008-08-01

The gastrin-releasing peptide receptor (GRP-R) is expressed in several normal human tissues and is overexpressed in various human tumors including breast, prostate, small-cell lung cancer and pancreatic cancer. Recently, 99mTc-EDDA/HYNIC-[Lys]-bombesin (99mTc-HYNIC-BN) was reported as a radiopharmaceutical with high stability in human serum, specific cell GRP-R binding and rapid cell internalization. The aim of this study was to determine the biokinetics and dosimetry of 99mTc-HYNIC-BN and the feasibility of using this radiopharmaceutical to image GRP-R in four early breast cancer patients and seven healthy women. Whole-body images were acquired at 20, 90, 180 min, and 24 h after 99mTc-HYNIC-BN administration. The same regions of interest were drawn around source organs on each time frame and regions of interest were converted to activity (conjugate view counting method). The image sequence was used to extrapolate 99mTc-HYNIC-BN time-activity curves in each organ to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. 99mTc-HYNIC-BN had a rapid blood clearance with mainly renal excretion. No statistically significant differences (P>0.05) in the radiation-absorbed doses among cancer patients and healthy women were observed. The average equivalent doses (n=11) were 24.8+/-8.8 mSv (kidneys), 7.3+/-1.8 mSv (lungs), 6.5+/-4.0 mSv (breast), 2.0+/-0.3 mSv (pancreas), 1.6+/-0.3 mSv (liver), 1.2+/-0.2 mSv (ovaries), and 1.0+/-0.2 mSv (red marrow). The effective dose was 3.3+/-0.6 mSv. The images showed well-differentiated concentration of 99mTc-HYNIC-BN in cancer mammary tissue. All the absorbed doses were comparable with those known for most of the 99mTc studies. 99mTc-HYNIC-BN shows high tumor uptake in breasts with malignant tumors so it is a promising imaging radiopharmaceutical to target site-specific early breast cancer. The results obtained warrant a further clinical study to determine specificity/sensibility of 99mTc-HYNIC-BN.

Tc-99m TRODAT uptake in an osteoid tumor of clivus.

PubMed

Taywade, Sameer; Tripathi, Madhavi; Tandon, Vivek; Das, Chandan Jyoti; Damle, Nishikant Avinash; Shamim, Shamim Ahmed; Thukral, Parul; Bal, Chandrasekhar

2016-01-01

Tc-99m TRODAT is cocaine analog and binds to the dopamine transporter in vivo . Tc-99m TRODAT single-photon emission computed tomography/computed tomography. (SPECT/CT) is useful for demonstrating presynaptic dopaminergic dysfunction in patients with Parkinsonism. However, few reports have shown extrastriatal uptake of Tc-99m TRODAT. We present the case of a 67-year-old male who underwent Tc-99m TRODAT SPECT/CT for evaluation of Parkinsonism. In addition to tracer binding in the striatum, tracer uptake was noted in an osteoid tumor of the clivus. Integrated SPECT/CT enabled precise localization and characterization of the extrastriatal site of tracer binding and emphasizes the importance of such coincidental findings.

Effective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan.

PubMed

Jing, Hongli; Li, Fang; Zhuang, Hongming; Wang, Zhenghua; Tian, Jian; Xing, Xiaoping; Jin, Jin; Zhong, Dingrong; Zhang, Jingjing

2013-11-01

Tumor-induced osteomalacia (TIO) is an endocrine disorder caused by tumors producing excessive fibroblast growth factor-23 (FGF-23). The causative tumors are generally small, slow-growing benign mesenchymal tumors. The only cure of the disease depends on resection of the tumors, which are extremely difficult to localize due to their small sizes and rare locations. Since these tumors are known to express somatostatin receptors, this research was undertaken to evaluate efficacy of [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body imaging in this clinical setting Images of 99mTc-HYNIC-TOC scans and clinical chart from 183 patients with hypophosphatemia and clinically suspected TIO were retrospectively reviewed. The scan findings were compared to the results of histopathological examinations and clinical follow-ups. Among 183 patients, 72 were confirmed to have TIO while 103 patients were found to have other causes of hypophosphatemia. The possibility of TIO could not be either diagnosed or excluded in the remaining 8 patients. For analytical purposes, these 8 patients who could neither be diagnosed nor excluded as having TIO were regarded as having the disease, bringing the total of TIO patients to 80. The 99mTc-HYNIC-TOC scan identified 69 tumors in 80 patients with TIO, which rendered a sensitivity of 86.3% (69/80). 99mTc-HYNIC-TOC scintigraphy excluded 102 patients without TIO with a specificity of 99.1% (102/103). The overall accuracy of 99mTc-HYNIC-TOC whole body scan in the localization of tumors responsible for osteomalacia is 93.4% (171/183). Whole body 99mTc-HYNIC-TOC imaging is effective in the localization of occult tumors causing TIO. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Structure and Properties of fac-[Re(I)(CO)3(NTA)](2-) (NTA(3-) = Trianion of Nitrilotriacetic Acid) and fac-[Re(I)(CO)3(L)](n-) Analogues Useful for Assessing the Excellent Renal Clearance of the fac-[(99m)Tc(I)(CO)3(NTA)](2-) Diagnostic Renal Agent.

PubMed

Klenc, Jeffrey; Lipowska, Malgorzata; Abhayawardhana, Pramuditha L; Taylor, Andrew T; Marzilli, Luigi G

2015-07-06

We previously identified two new agents based on the [(99m)Tc(V)O](3+) core with renal clearances in human volunteers 30% higher than that of the widely used clinical tracer (99m)Tc-MAG3 (MAG3(5-) = penta-anion of mercaptoacetyltriglycine). However, renal agents with even higher clearances are needed. More recently, we changed our focus from the [(99m)Tc(V)O](3+) core to the discovery of superior tracers based on the fac-[(99m)Tc(I)(CO)3](+) core. Compared to (99m)Tc-MAG3, fac-[(99m)Tc(I)(CO)3(NTA)](2-) (NTA(3-) = trianion of nitrilotriacetic acid) holds great promise by virtue of its efficient renal clearance via tubular secretion and the absence of hepatobiliary elimination, even in patients with severely reduced renal function. We report here NMR, molecular (X-ray) structure, and solution data on fac-[Re(I)(CO)3(NTA)](2-) with a -CH2CO2(-) dangling monoanionic chain and on two fac-[Re(I)(CO)3(L)](-) analogues with either a -CH2CONH2 or a -CH2CH2OH dangling neutral chain. In these three fac-[Re(I)(CO)3(L)](n-) complexes, the fac-[Re(I)(CO)3(N(CH2CO2)2)](-) moiety is structurally similar and has similar electronic properties (as assessed by NMR data). In reported and ongoing studies, the two fac-[(99m)Tc(I)(CO)3(L)](-) analogues with these neutral dangling chains were found to have pharmacokinetic properties very similar to those of fac-[(99m)Tc(I)(CO)3(NTA)](2-). Therefore, we reach the unexpected conclusion that in fac-[(99m)Tc(I)(CO)3(L)](n-) agents, renal clearance is affected much more than anticipated by features of the core plus the chelate rings (the [(99m)Tc(I)(CO)3(N(CH2CO2)2)](-) moiety) than by the presence of a negatively charged dangling carboxylate chain.

Stability of stabilized 99mTc-D,L-HMPAO stored in vials and syringes.

PubMed

Del Carmen Plancha-Mansanet, Maria; Caballero-Calabuig, Elisa; Félix-Fontestad, Jesús; Reyes-Ojeda, María Dolores; Sopena-Novales, Pablo; Abreu-Sánchez, Pedro; Del Carmen Cano-Terol, Maria; Sopena-Monforte, Ramón

2008-12-01

Our objective was to determine the stability of stabilized (99m)Tc-hexamethylpropylene amine oxime ((99m)Tc-d,l-HMPAO) dispensed by vial and syringe, with the storage time and labeling activity varied. (99m)Tc-d,l-HMPAO was labeled according to the manufacturer's instructions, but with modification of the (99m)TcO(4)Na activity. Two groups were prepared: 1,110 MBq (30 mCi) and 2,600-3,700 MBq (70.3-100 mCi). Five minutes after labeling, the radiochemical purity (RCP) of the vial content was determined. Afterward, the same activity was distributed into two 2-mL syringes and into the manufacturer's vial. In one of the syringes, the radiopharmaceutical stayed in contact with the needle for 4 h. At 2 and 4 h after labeling, the RCP of the vial and syringe content was checked and compared. The mean RCP of stabilized (99m)Tc-d,l-HMPAO labeled with 1,110 MBq (30 mCi) and stored in a vial decreased from 93.1% at 5 min to 92.1% at 2 h and to 91.1% at 4 h. With storage in a syringe, the RCP decreased from 89.8% at 2 h to 88.7% at 4 h. This diminution increased for labeling with higher activities (2,600-3,700 MBq [70.3-100 mCi]), ranging from 91.4% at 5 min, 89.0% at 2 h, and 85.3% at 4 h in a vial and from 85.9% at 2 h to 80.2% in a syringe. (99m)TcO(2) and secondary (99m)Tc-HMPAO were the main impurities at t = 0. (99m)TcO(4)(-) was an impurity that increased with time in both vials and syringes but significantly so in syringes. All these impurities were higher with labeling activities in the range of 2,600-3,700 MBq (70.3-100 mCi). Contact of the needle with (99m)Tc-d,l-HMPAO sharply decreased the RCP to 57.1% at 4 h. The RCP of stabilized (99m)Tc-d,l-HMPAO decreases significantly in both vials and syringes with high labeling activities. The product is less stable when stored in a syringe than in a vial. The fraction of dose in contact with the needle affects the RCP results.

Synthesis of Tc-99m labeled 1,2,3-triazole-4-yl c-met binding peptide as a potential c-met receptor kinase positive tumor imaging agent.

PubMed

Kim, Eun-Mi; Joung, Min-Hee; Lee, Chang-Moon; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Kim, Dong Wook

2010-07-15

The mesenchymal-epithelial transition factor (c-Met), which is related to tumor cell growth, angiogenesis and metastases, is known to be overexpressed in several tumor types. In this study, we synthesized technetium-99m labeled 1,2,3-triazole-4-yl c-Met binding peptide (cMBP) derivatives, prepared by solid phase peptide synthesis and the 'click-to-chelate' protocol for the introduction of tricarbonyl technetium-99m, as a potential c-Met receptor kinase positive tumor imaging agent, and evaluated their in vitro c-Met binding affinity, cellular uptake, and stability. The (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12, [(99m)Tc(CO)(3)]13, and [(99m)Tc(CO)(3)]14) were prepared in 85-90% radiochemical yields. The cold surrogate cMBP derivatives, [Re(CO)(3)]12, [Re(CO)(3)]13, and [Re(CO)(3)]14, were shown to have high binding affinities (0.13 microM, 0.06 microM, and 0.16 microM, respectively) to a purified cMet/Fc chimeric recombinant protein. In addition, the in vitro cellular uptake and inhibition studies demonstrated the high specific binding of these (99m)Tc labeled cMBP derivatives ([(99m)Tc(CO)(3)]12-14) to c-Met receptor positive U87MG cells. 2010 Elsevier Ltd. All rights reserved.

Prospective Randomized Trial of Use of In-House Prepared Low-Cost Radiopharmaceutical Versus Commercial Radiopharmaceutical for Sentinel Lymph Node Biopsy in Patients with Early Stage Invasive Breast Cancer.

PubMed

Agarwal, Gaurav; Rajan, Sendhil; Mayilvaganan, Sabaretnam; Mishra, Anjali; Krishnani, Narendra; Gambhir, Sanjay

2018-05-01

The current standard-of-care for surgical staging of the axilla in clinically node-negative (N0) early breast cancers is sentinel lymph node biopsy (SLNB), which requires expensive radiopharmaceuticals for efficacious results. In-house produced low-cost radiopharmaceuticals may be the solution and have shown efficacy in earlier observational/pilot studies. We compared SLNB using in-house prepared radiopharmaceutical ( 99m Tc-Antimony-colloid) versus commercially marketed radiopharmaceutical ( 99m Tc-Sulphur-colloid) in this prospective randomized study. 78 clinically N0 early breast cancer patients (T1/2, N0 stages), undergoing primary surgery were prospectively randomized 1:1 into two groups; to receive SLNB using methylene blue, and either 99m Tc-Antimony colloid (Group-1) or   99m Tc-Sulphur colloid (Group-2). Completion axillary dissection was done in all (validation SLNB). SLNB indices were compared between the groups. The groups were comparable with regard to age, stage, tumour size, hormone receptors and HER2neu status. Cost of the in-house prepared 99m Tc-antimony colloid was 16-times lesser compared to 99m Tc-sulphur colloid. SLN identification rates (IR) in Groups 1 and 2 were 100 and 97.4% respectively, (p > 0.05). False negative rates (FNR) in Group 1 and 2 were 6.3% (1/16 patients) and 7.7% (1/13 patients), respectively, (p > 0.05). There were no major allergic reactions in either group. In this prospective randomized trial on early breast cancer patients, accuracy of SLNB was comparable using in-house prepared, 99m Tc-antimony colloid and commercially marketed 99m Tc-sulphur colloid as radiopharmaceutical, while 99m Tc-antimony colloid was much cheaper than 99m Tc-sulphur colloid.

[Contamination levels to room air arising from the use of 99mTc-gas and prevention from the contamination].

PubMed

Komatani, A; Akutsu, T; Yamaguchi, K; Onodera, Y; Manaka, Y; Takahashi, K

1996-04-01

99mTc-gas (TECHNEGAS) is a 99mTc-labeled micro-aerosol which is considered to have different behavior from 133Xe or 81mKr gas. In order to estimate contamination levels to room air arising from the use of 99mTc-gas, filtered expired air during administration and 1, 2, 3, 5, 10 min after the administration were collected in each polyethylene bag. Radioactivities of the polyethylene bags, used filter and the lung were measured with 3-head scintillation camera. The activity of the expired air diminished within 6-10 min and about 5% of whole discharged 99mTc-gas was released to room air. The activity of the used filter was two times of the lung. According to these results, it is recommended that the 99mTc-gas may be administrated in a exclusive room. The administrated patient and used filter must be remain in the exclusive room.

The distribution of 99mTc-EHDP in the tissues of the dog and its application in the assessment of fracture healing.

PubMed

Hughes, S

1977-07-01

Technetium-labelled ethane hydroxydiphosphonate (99mTc-EHDP) is a commonly used bone-scanning agent. After injection it leaves the circulation to enter bone and to be cleared by the kidney. The transcapillary exchange of 99mTc-EHDP in bone was examined and found to be low. The capillary movement was compared with that of sucrose, a freely diffusible substance, and it was found that the permeability ratio of 99mTc-EHDP to 14C-sucrose was similar to the diffusion coefficient ratio, suggesting that 99mTc-EHDP passes through the capillaries by the process of passive diffusion. The renal clearance of 99mTc-EHDP was 24 ml/min and was unaffected by the action of parathyroid hormone. After a fracture the bone blood flow increases, although the transcapillary extraction of 99mTc-EHDP does not change. This is because there is an increase, from recruitment and dilatation of capillaries, in the surface area available for exchange. Therefore the increased isotopic activity seen on a bone scan after a fracture is primarily related to an increase in bone blood supply from capillary enhancement within the cortex.

Development and study of 99mTc-1-Thio-D-glucose for visualization of malignant tumors

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Skuridin, V.

2017-09-01

The preclinical studies of 99mTc-1-Thio-D-glucose, a new tumor-seeking agent based on technetium-99m-labeled glucose derivative, were conducted, and the feasibility of using this radiopharmaceutical for tumor visualization was studied. The preclinical studies were carried out strictly in accordance with the local legislation and were regulated by the generally accepted research standards. 99mTc-1-Thio-D-glucose was found to have optimal pharmacokinetic and physico-chemical properties for diagnostic imaging and was proved to belong to the low-toxic substances. The potential utility of 99mTc-1-thio-D-glucose for tumor imaging was studied in vitro and in vivo models. The present study demonstrated that 99mTc-1-Thio-D-glucose is a prospective radiopharmaceutical for cancer visualization.

Urine interleukin-6, interleukin-8 and transforming growth factor β1 in infants with urinary tract infection and asymptomatic bacteriuria

PubMed Central

Krzemień, Grażyna; Turczyn, Agnieszka; Pańczyk-Tomaszewska, Małgorzata

2016-01-01

Introduction Urinary tract infection (UTI) occurs in 1.1% of girls and 1.4% of boys during the first year of life. Asymptomatic bacteriuria (ABU) is usually detected incidentally in 0.9% of girls and 2.5% of boys at this age. The aim of the study was to assess the usefulness of measurement of pro-inflammatory urine interleukin (IL)-6 and IL-8 concentrations and anti-inflammatory transforming growth factor β1 (TGF-β1) level in infants with febrile UTI, non-febrile UTI and ABU. Material and methods A total of 35 children, mean age 6.14 ±3.47 months, were divided into three groups: group I – febrile UTI (n = 13), group II – non-febrile UTI (n = 13) and group III – ABU (n = 9). At the time of enrollment urine IL-6, IL-8, TGF-β1 and serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured. Renal ultrasound was performed in all children, 99mTc-dimercaptosuccinic acid scintigraphy (DMSA) and voiding cystourethrography in children with UTI. Results Urine concentrations of IL-6 and IL-8 were significantly higher in febrile UTI compared to those with non-febrile UTI and ABU (p < 0.5, p < 0.01) and positively correlated with CRP, ESR and WBC (p < 0.01). Urine levels of TGF-β1 were significantly higher in children with febrile UTI compared to those with ABU (p < 0.05) and positively correlated with WBC (p < 0.01). Inflammatory changes in the DMSA scan were detected in 66.6% of children with UTI. No significant difference in frequency of an abnormal DMSA scan compared to a normal scan was found in groups with febrile and non-febrile UTI. No relations between urine cytokines, systemic inflammatory markers and changes in DMSA scan were observed. The cutoff value for detection of inflammatory changes in the DMSA scan for IL-8 was 120 pg/mg creatinine (Cr) and 40 pg/mg Cr for TGF-β1. Based on this value, the sensitivity for IL-8 was 58.3%, specificity 100% and for TGF-β1 66.7% and 83.7%, respectively. Conclusions We found significant differences in children with febrile UTI and ABU regarding urine IL-6, IL-8 and TGF-β1 levels. Urine cytokines and systemic inflammatory markers do not differentiate between upper and lower UTI in infants. PMID:27833443

The absorption of (99m)Tc-alendronate given by rectal route in rabbits.

PubMed

Asikoğlu, Makbule; Ozguney, Isik; Ozcan, Ipek; Orumlu, Oya; Guneri, Tamer; Koseoğlu, Kamil; Ozkilic, Hayal

2008-01-01

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%-1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m ((99m)Tc) by direct method. The radiochemical characterization of the (99m)Tc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of (99m)Tc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing (99m)Tc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The (99m)Tc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of (99m)Tc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

Quality of 99mTcO4- from 99Mo Produced by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Nagai, Yasuki; Nakahara, Yuto; Kawabata, Masako; Hatsukawa, Yuichi; Hashimoto, Kazuyuki; Saeki, Hideya; Motoishi, Shoji; Ohta, Akio; Shiina, Takayuki; Kawauchi, Yukimasa

2017-05-01

The pharmaceutical quality of 99mTc pertechnetate solution obtained from 99Mo, the 100Mo(n,2n) reaction product, was investigated for the first time with an emphasis on the nonradioactive Mo content and endotoxin concentration. They were less than the tolerance dose given in international guidelines and the established upper limit in an international pharmacopoeia, respectively. Four other quality control tests commonly used for a commercially available 99mTc pertechnetate solution also demonstrated to meet the United States Pharmacopeia requirements. The results strongly support that the thermochromatographic separation method used to separate 99mTc from 99Mo can be a promising substitute for the fission product 99Mo.

Synthesis and biological evaluation of new diisocyanide- and triisocyanide-99mTc complexes.

PubMed

Chemin, N; du Moulinet d'Hardemare, A; Bouquillon, S; Fagret, D; Vidal, M

1996-01-01

This paper describes the synthesis of four new polyisocyanides (three diisocyanides and one triisocyanide). The complexation of 99mTc with these ligands is also studied through chromatography and revealed the formation of hexacoordinated 99mTc+1 complexes. Finally, biodistributions of these complexes in mice are given and compared. Heart captations are lower than the ones with [99mTc(MIBI)6]+ but remain constant and a satisfactory lungs clearance, probably due to the metabolization of the ligands, is observed.

[Calculation of the partial function of the kidney with DMSA in pediatrics: is the evaluation of the geometric mean necessary?].

PubMed

Porn, U; Rossmüller, B; Alalp, S; Fischer, S; Dresel, S; Hahn, K

2001-08-01

For assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimercaptosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 +/- 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256, 300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr)]. The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p < 0.01). The mean difference between the PFgeom and the PFdors was 1.5 +/- 1.4%. A difference > or = 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference > 5% did not show any renal abnormality. The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differential renal function in orthotopic kidneys, so that in these cases the anterior view is not necessary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.

Potential Ways to Address Shortage Situations of 99Mo/99mTc.

PubMed

Filzen, Leah M; Ellingson, Lacey R; Paulsen, Andrew M; Hung, Joseph C

2017-03-01

99m Tc, the most common radioisotope used in nuclear medicine, is produced in a nuclear reactor from the decay of 99 Mo. There are only a few aging nuclear reactors around the world that produce 99 Mo, and one of the major contributors, the National Research Universal (Canada), ceased production on October 31, 2016. The National Research Universal produced approximately 40% of the world's 99 Mo supply, so with its shut down, shortages of 99 Mo/ 99m Tc are expected. Methods: Nuclear pharmacies and nuclear medicine departments throughout the United States were contacted and asked to provide their strategies for coping with a shortage of 99 Mo/ 99m Tc. Each of these strategies was evaluated on the basis of its effectiveness for conserving 99m Tc while still meeting the needs of the patients. Results: From the responses, the following 6 categories of strategies, in order of importance, were compiled: contractual agreements with commercial nuclear pharmacies, alternative imaging protocols, changes in imaging schedules, software use, generator management, and reduction of ordered doses or elimination of backup doses. Conclusion: The supply chain of 99 Mo/ 99m Tc is quite fragile; therefore, being aware of the most appropriate coping strategies is crucial. It is essential to build a strong collaboration between the nuclear pharmacy and nuclear medicine department during a shortage situation. With both nuclear medicine departments and nuclear pharmacies implementing viable strategies, such as the ones proposed, the amount of 99m Tc available during a shortage situation can be maximized. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Effects of amino acids on melanoma targeting and clearance properties of Tc-99m-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2013-11-14

The purpose of this study was to examine the effects of amino acids on melanoma targeting and clearance properties of new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-Lys-(Arg(11))CCMSH {c[Arg-Ser-Asp-DTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RNleD-Lys-(Arg(11))CCMSH, RPheD-Lys-(Arg(11))CCMSH, and RdPheD-Lys-(Arg(11))CCMSH peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of (99m)Tc-RSD-Lys-(Arg(11))CCMSH, (99m)Tc-RFD-Lys-(Arg(11))CCMSH, and (99m)Tc-RfD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe, and dPhe increased the MC1 receptor binding affinities of the peptides, whereas the substitution of Gly with Nle decreased the MC1 receptor binding affinity of the peptide. (99m)Tc-RSD-Lys-(Arg(11))CCMSH exhibited the highest melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these (99m)Tc-peptides. The B16/F1 melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RSD-Lys-(Arg(11))CCMSH as an imaging probe. It is desirable to reduce the renal uptake of (99m)Tc-RSD-Lys-(Arg(11))CCMSH to facilitate its potential therapeutic application.

(99m)Tc-HYNIC-TOC scintigraphy in evaluation of active Graves' ophthalmopathy (GO).

PubMed

Sun, Hua; Jiang, Xu-Feng; Wang, Shu; Chen, Hao-Yan; Sun, Jiao; Li, Pei-Yong; Ning, Guang; Zhao, Yong-Ju

2007-06-01

A promising radiopharmaceutical (99m)Tc-HYNIC-TOC ((99m)Tc-HYNIC-Octreotide) can be applied for somatostatin receptor scintigraphy with the potential to replace Indium-111 labeled somatostatin analogus. Here we evaluate whether orbital (99m)Tc-HYNIC-TOC scintigraphy can be used as a Graves' ophthalmopathy (GO) activity parameter to predict the retrobulbar irradiation response. Orbital (99m)Tc-HYNIC-TOC scintigraphy was performed on 14 consecutive patients demonstrating moderated to severe Graves' ophthalmopathy. The patients were treated with retrobulbar irradiation following the octreoscan and the response to this therapy was assessed at 3 months after the start of treatment. The orbital (99m)Tc-HYNIC-TOC uptake was calculated to assess the effects of treatment. Among the 14 GO patients, eight (57.1%) responded to retrobulbar radiotherapy; six (42.9%) showed no change. We compared the eight responders and six non-responders in terms of orbital (99m)Tc-HYNIC-TOC uptake, using the orbital/occipital ratio. On the 4-h (99m)Tc-HYNIC-TOC scintigraphy, responders had a higher orbital/occipital uptake ratio than the no-responders (P = 0.001). A significant correlation was found between the orbital/occipital ratio and the clinical activity score (CAS) (P = 0.034). The Receiving-Operator-Characteristic curve showed the best threshold for discriminating active and inactive disease was 1.40 (sensitivity, 100%; specificity, 83.3%). In the responders group, all these eight patients had positive scintigraphy. While there were five patients who had negative scintigraphy in the non-responders group. Orbital (99m)Tc-HYNIC-TOC scintigraphy can be a useful method for the estimation of disease activity and prediction the response to subsequent radiotherapy in GO patient. And the patients with positive octreoscan were more likely to respond to irradiation.

Development of kit formulations for (99m) TcN-MPO: a cationic radiotracer for myocardial perfusion imaging.

PubMed

Zheng, Yumin; Ji, Shundong; Tomaselli, Elena; Liu, Shuang

2014-07-01

The objective of this study was to develop a kit formulation for [(99m) TcN(mpo)(PNP5)](+) (MPO = 2-mercaptopyridine oxide), ((99m) TcN-MPO) to support its clinical evaluations as a SPECT radiotracer. Radiolabeling studies were performed using three different formulations (two-vial formulation and single-vial formulations with/without SnCl2 ) to explore the factors influencing radiochemical purity (RCP) of (99m) TcN-MPO. We found that the most important factor affecting the RCP of (99m) TcN-MPO was the purity of PNP5. (99m) TcN-MPO was prepared >98% RCP (n = 20) using the two-vial formulation. For single-vial formulations with/without SnCl2 , β-cyclodextrin (β-CD) is particularly useful as a stabilizer for PNP5. The RCP of (99m) TcN-MPO was 95-98% using β-CD, but its RCP was only 90-93% with γ-cyclodextrin (γ-CD). It seems that PNP5 fits better into the inner cavity of β-CD, which forms more stable inclusion complex than γ-CD in the single-vial formulations. The results from biodistribution and imaging studies in Sprague-Dawley rats clearly demonstrated biological equivalence of three different formulations. Single photon-emission computed tomography data suggested that high quality images could be obtained at 0-30-min post-injection without significant interference from the liver radioactivity. Considering the ease for (99m) Tc-labeling and high RCP of (99m) TcN-MPO, the non-SnCl2 single-vial formulation is an attractive choice for future clinical studies. Copyright © 2014 John Wiley & Sons, Ltd.

Values of (99m)Tc-methoxyisobutylisonitrile imaging after first-time large-dose (131)I therapy in treating differentiated thyroid cancer.

PubMed

Pan, Xiaomei; Duan, Dong; Zhu, Yuquan; Pang, Hua; Guan, Lili; Lv, Zhixiang

2016-01-01

The aim of this study is to investigate the use of (99m)Tc-methoxyisobutylisonitrile (MIBI) imaging for evaluating the treatment response of differentiated thyroid cancer (DTC) after the first administration of a high dose of (131)I. Patients with DTC who received (131)I therapy underwent (99m)Tc-MIBI imaging after successive increases in the therapeutic dose of (131)I, and the serum levels of thyroglobulin (Tg) were measured. A total of 191 patients were enrolled in the final analysis, including 65 metastases and/or thyroid remnant-positive patients (22 patients with metastases and 43 patients with thyroid remnants). The sensitivity of (99m)Tc-MIBI imaging for detecting positive cases and thyroid remnants was 56.9% and 39.5%, respectively, which was significantly lower than that of (131)I imaging (92.3% and 100%, respectively, P<0.01 for both). The sensitivity of (99m)Tc-MIBI imaging for detecting metastases was 90.9%, which was slightly higher than that of (131)I imaging (77.3%, P>0.05). The Tg levels in the positive group were significantly higher than that in the negative group (P<0.01). In addition, the Tg levels in the (99m)Tc-MIBI(+)/(131)I(-) group were significantly higher than that in the (131)I(+)/(99m)Tc-MIBI group (P<0.05). After the first (131)I therapy, although (99m)Tc-MIBI imaging was able to detect the existence of metastatic lesions in patients with DTC better, its assessment for the removal efficiency of thyroid remnants was unsatisfactory. The results of (99m)Tc-MIBI imaging showed good correlations with the Tg level.

Cutoff value of thyroid uptake of (99m)Tc-pertechnetate to discriminate between Graves' disease and painless thyroiditis: a single center retrospective study.

PubMed

Uchida, Toyoyoshi; Suzuki, Ruriko; Kasai, Takatoshi; Onose, Hiroyuki; Komiya, Koji; Goto, Hiromasa; Takeno, Kageumi; Ishii, Shinya; Sato, Junko; Honda, Akira; Kawano, Yui; Himuro, Miwa; Yamada, Emiko; Yamada, Tetsu; Watada, Hirotaka

2016-01-01

Thyroid uptake of (99m)Tc-pertechnetate is a useful way to determine the cause of thyrotoxicosis. In daily clinical practice, (99m)Tc-pertechnetate uptake is used to discriminate between Graves' disease and painless thyroiditis when clinical information is not enough to make the distinction. However, since the optimal cutoff value of (99m)Tc-pertechnetate uptake has not yet been elucidated, our aim was to determine this value. We recruited patients with thyrotoxicosis in whom (99m)Tc-pertechnetate uptake was measured in clinical settings between 2009 and 2013. Three experienced endocrinologists (who were blinded to the value of (99m)Tc-pertechnetate uptake and initial treatment) diagnosed the cause of thyrotoxicosis based on thyrotropin, free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels, and by ultrasound findings and using images of thyroid uptake of (99m)Tc-pertechnetate without the actual values. Ninety-four patients diagnosed as having Graves' disease or painless thyroiditis were finally included. According to the diagnosis, the optimal cutoff value of (99m)Tc-pertechnetate uptake was determined by receiver operating characteristics analysis. A cutoff value of 1.0% provided optimal sensitivity and specificity of 96.6% and 97.1%, respectively. Then, its validity was confirmed in 78 patients with confirmed Graves' disease or painless thyroiditis diagnosed at another institute. Applying this cutoff value to the patients with thyrotoxicosis revealed positive and negative predictive values for Graves' disease of 100% and 88.9%, respectively. In conclusion, a cutoff value for (99m)Tc-pertechnetate uptake of 1.0% was useful to discriminate between Graves' disease and painless thyroiditis.

Development of (99m)Tc-labeled asymmetric urea derivatives that target prostate-specific membrane antigen for single-photon emission computed tomography imaging.

PubMed

Kimura, Hiroyuki; Sampei, Sotaro; Matsuoka, Daiko; Harada, Naoya; Watanabe, Hiroyuki; Arimitsu, Kenji; Ono, Masahiro; Saji, Hideo

2016-05-15

Prostate-specific membrane antigen (PSMA) is expressed strongly in prostate cancers and is, therefore, an attractive diagnostic and radioimmunotherapeutic target. In contrast to previous reports of PMSA-targeting (99m)Tc-tricarbonyl complexes that are cationic or lack a charge, no anionic (99m)Tc-tricarbonyl complexes have been reported. Notably, the hydrophilicity conferred by both cationic and anionic charges leads to rapid hepatobiliary clearance, whereas an anionic charge might better enhance renal clearance relative to a cationic charge. Therefore, an improvement in rapid clearance would be expected with either cationic or anionic charges, particularly anionic charges. In this study, we designed and synthesized a novel anionic (99m)Tc-tricarbonyl complex ([(99m)Tc]TMCE) and evaluated its use as a single-photon emission computed tomography (SPECT) imaging probe for PSMA detection. Direct synthesis of [(99m)Tc]TMCE from dimethyl iminodiacetate, which contains both the asymmetric urea and succinimidyl moiety important for PSMA binding, was performed using our microwave-assisted one-pot procedure. The chelate formation was successfully achieved even though the precursor included a complicated bioactive moiety. The radiochemical yield of [(99m)Tc]TMCE was 12-17%, with a radiochemical purity greater than 98% after HPLC purification. [(99m)Tc]TMCE showed high affinity in vitro, with high accumulation in LNCaP tumors and low hepatic retention in biodistribution and SPECT/CT studies. These findings warrant further evaluation of [(99m)Tc]TMCE as an imaging agent and support the benefit of this strategy for the design of other PSMA imaging probes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Amino Acids on Melanoma Targeting and Clearance Properties of Tc-99m-Labeled Arg-X-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

Flook, Adam M.; Yang, Jianquan; Miao, Yubin

2013-01-01

The purpose of this study was to examine the effects of amino acids on melanoma targeting and clearance properties of new 99mTc-labeled Arg-X-Asp-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptides. RSD-Lys-(Arg11)CCMSH {c[Arg-Ser-Asp-dTyr-Asp]-Lys-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RNleD-Lys-(Arg11)CCMSH, RPheD-Lys-(Arg11)CCMSH and RdPheD-Lys-(Arg11)CCMSH peptides were synthesized and evaluated for their melanocortin-1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of 99mTc-RSD-Lys-(Arg11)CCMSH, 99mTc-RFD-Lys-(Arg11)CCMSH and 99mTc-RfD-Lys-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The substitution of Gly with Ser, Phe and dPhe increased the MC1 receptor binding affinities of the peptides, whereas the substitution of Gly with Nle decreased the MC1 receptor binding affinity of the peptide. 99mTc-RSD-Lys-(Arg11)CCMSH exhibited the highest melanoma uptake (18.01 ± 4.22% ID/g) and the lowest kidney and liver uptake among these 99mTc-peptides. The B16/F1 melanoma lesions could be clearly visualized by SPECT/CT using 99mTc-RSD-Lys-(Arg11)CCMSH as an imaging probe. It is desirable to reduce the renal uptake of 99mTc-RSD-Lys-(Arg11)CCMSH to facilitate its potential therapeutic application. PMID:24131154

Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0,Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization?

PubMed

Storch, Daniel; Béhé, Martin; Walter, Martin A; Chen, Jianhua; Powell, Pia; Mikolajczak, Renata; Mäcke, Helmut R

2005-09-01

Radiolabeled somatostatin analogs are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin receptor-positive tumors. The aim of this study was to compare 3 somatostatin analogs designed for the labeling with (99m)Tc (where HYNIC is 6-hydrazinopyridine-3-carboxylic acid): 6-hydrazinopyridine-3-carboxylic acid(0)-octreotide (HYNIC-OC/(99m)Tc-(1)), [HYNIC(0),Tyr(3)]octreotide (HYNIC-TOC/(99m)Tc-(2)), and [HYNIC(0),Tyr(3),Thr(8)]octreotide (HYNIC-TATE/(99m)Tc-(3)), using ethylenediamine-N,N'-diacetic acid (EDDA) as a coligand. In addition, we compared the (99m)Tc-labeled peptides [(111)In-diethylenetriaminepentaacetic acid(0)]octreotide ([(111)In-DTPA]-OC) and [(111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(0),Tyr(3),Thr(8)]octreotide ([(111)In-DOTA]-TATE) with regard to the rate of internalization and the biodistribution in AR4-2J (expressing the somatostatin receptor subtype 2) tumor-bearing rats. The main attention was directed toward a potential correlation between the rate of internalization and the tumor or pancreas uptake. Synthesis was performed on solid phase using a standard Fmoc strategy. Internalization was studied in cell culture (AR4-2J) and biodistribution was studied using a Lewis rat tumor model (AR4-2J). The 5 radiopeptides showed a specific internalization into AR4-2J cells in culture (as shown by blocking experiments). The rate of internalization of the 5 radiopeptides differed significantly according to the following order: (99m)Tc-(1) approximately = [(111)In-DTPA]-OC < (99m)Tc-(2) < (99m)Tc-(3) approximately = [(111)In-DOTA]-TATE. All radiopeptides displayed a rapid blood clearance and a fast clearance from all somatostatin receptor-negative tissues predominantly via the kidneys. A receptor-specific uptake of radioactivity was observed for all compounds in somatostatin receptor-positive organs such as the pancreas, the adrenals, and the stomach. After 4 h, the uptake in the AR4-2J tumor was comparable for (99m)Tc-(2) (3.85 +/- 1.0 injected dose per gram tissue (%ID/g)), (99m)Tc-(3) (3.99 +/- 0.58%ID/g), and [(111)In-DOTA]-TATE (4.12 +/- 0.74%ID/g) but much lower for [(111)In-DTPA]-OC (0.99 +/- 0.08%ID/g) and (99m)Tc-(1) (0.70 +/- 0.13%ID/g). The specificity was determined by blocking experiments using a large excess of [Tyr(3)]octreotide. (99m)Tc-(3) displayed the highest tumor-to-kidney ratio (2.5:1), followed by (99m)Tc(2) (1.9:1) and [(111)In-DOTA]-TATE (1.7:1). These data show that the 5 radiopeptides are specific radioligands for the somatostatin receptor subtype 2. The rate of internalization correlates with the uptake in the tumor (R(2) = 0.75; P = 0.026) and pancreas (R(2) = 0.98; P = 7.4.10(-5)). [Tyr(3),Thr(8)]octreotide derivatives show superiority over the corresponding octreotide and [Tyr(3)]octreotide derivatives, indicating that [(111)In-DOTA]-TATE and [(99m)Tc/EDDA/HYNIC]-TATE are suitable candidates for clinical studies.

Tc-99m Labeled carrier for imaging

DOEpatents

Henze, Eberhard

1984-01-01

Novel radionuclide imaging agents, having particular application for lymphangiography are provided by non-covalently binding Tc-99m to a pharmaceutically acceptable cross-linked polysaccharide. Upon injection of the Tc-99m labeled polysaccharide into the blood stream, optimum contrast can be obtained within one hour.

99mTc-tagged chicken liver as a marker of solid food in the human stomach.

PubMed

Meyer, J H; MacGregor, I L; Gueller, R; Martin, P; Cavalieri, R

1976-04-01

Past measurement of gastric emptying of solid food in man has depended on external counting of surface-absorbed isotopes without verification that isotopic labels remain attached to solid food in the stomach. In this study chicken liver was isotopically labeled with 99mTc incorporated uniformly and intracellularly throughout the liver substance. In vitro studies showed less than 10% loss of 99mTc from liver incubated with pepsin HC1. By contrast, up to 90% of 51Cr absorbed to scrambled eggs became detached under similar conditions. In feeding experiments less than 10% of 99mTc was liberated from fed 99mTc liver, while significantly more 51Cr became detached from egg under identical intragastric conditions. We conclude that 99mTc-tagged chicken liver is an adequate marker of the rate of emptying of solid food and appears to be more reliable than 51Cr-labeled scrambled eggs from which 51Cr dissociates in the stomach.

Synthesis and characterization of fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] complexes (M = Re, (99m)Tc) with acetylacetone and curcumin as OO donor bidentate ligands.

PubMed

Triantis, Charalampos; Tsotakos, Theodoros; Tsoukalas, Charalampos; Sagnou, Marina; Raptopoulou, Catherine; Terzis, Aris; Psycharis, Vassilis; Pelecanou, Maria; Pirmettis, Ioannis; Papadopoulos, Minas

2013-11-18

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

Feasibility studies towards future self-sufficient supply of the 99Mo-99mTc isotopes with Japanese accelerators

PubMed Central

NAKAI, Kozi; TAKAHASHI, Naruto; HATAZAWA, Jun; SHINOHARA, Atsushi; HAYASHI, Yoshihiko; IKEDA, Hayato; KANAI, Yasukazu; WATABE, Tadashi; FUKUDA, Mitsuhiro; HATANAKA, Kichiji

2014-01-01

In order to establish a self-sufficient supply of 99mTc, we studied feasibilities to produce its parent nucleus, 99Mo, using Japanese accelerators. The daughter nucleus, 99mTc, is indispensable for medical diagnosis. 99Mo has so far been imported from abroad, which is separated from fission products generated in nuclear reactors using enriched 235U fuel. We investigated 99mTc production possibilities based on the following three scenarios: (1) 99Mo production by the (n, 2n) reaction by spallation neutrons at the J-PARC injector, LINAC; (2) 99Mo production by the (p, pn) reaction at Ep = 50–80 MeV proton at the RCNP cyclotron; (3) 99mTc direct production with a 20 MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for a scheme on a global scale, scenario (2) works in a local area, and both cases take a long time for negotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for 99mTc production. We here consider both the advantages and disadvantages among the three scenarios by taking account of the Japanese accelerator situation. PMID:25504230

Initial evaluation of 99m Tc-tricarbonyl-cyclopentadienyl fatty acids derivatives as SPECT tracers for myocardium.

PubMed

Liu, Jianping; Wang, Huan; Wang, Shuxia; Xue, Qianqian; Wang, Dawei; Wang, Hang; Zhang, Huabei

2017-05-15

Fatty acids are myocardial metabolic agent for detecting myocardial ischemia and infraction. However, no 99m Tc-labeled fatty acids had potential use in clinical practice. In this study, 99m Tc-CpTT-10-oxo-para-PPA (1d), 99m Tc-CpTT-11-oxo-para-PPA (2d), 99m Tc-CpTT-12-oxo-para-PPA (3d), 99m Tc-CpTT-11-oxo-ortho-PPA (4d), and 99m Tc-CpTT-11-oxo-meta-PPA (5d) were synthesized by a double ligand transfer reaction, and their biological behaviors were investigated. Compound 2d achieved good heart to blood ratio (3.39 at 5 min after intravenous), and 2d showed high-heart uptake of 6.20% ID/g at 5 minutes after injection. Compound 3d displayed a prolonged retention in the myocardium (1.43% ID/g at 60 min after injection). Radioactivity accumulation in the lungs, spleen, and blood was eliminated rapidly. In vivo, metabolite analysis presented that compound 6d may be metabolite of 2d through β-oxidation in tissue. Unfortunately, the biodistribution studies of 1d, 2d, 3d, 4d, and 5d showed fast heart clearance and poor heart to liver ratios, which suggested that the 5 99m Tc-labeled fatty acid analogues cannot be used for diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.

Preparation and comparative evaluation of 99m Tc-HYNIC-cNGR and 99m Tc-HYNIC-PEG2 -cNGR as tumor-targeting molecular imaging probes.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Kumar, Chandan; Sarma, Haladhar Dev; Banerjee, Sharmila

2018-02-01

The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG 2 -c(NGR), were synthesized, radiolabeled with 99m Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99m Tc-labeled HYNIC peptide could not be modulated through introduction of PEG 2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. Copyright © 2017 John Wiley & Sons, Ltd.

Modulation of in vivo distribution through chelator: Synthesis and evaluation of a 2-nitroimidazole-dipicolylamine-(99m)Tc(CO)3 complex for detecting tumor hypoxia.

PubMed

Mallia, Madhava B; Mittal, Sweety; Sarma, Haladhar D; Banerjee, Sharmila

2016-01-01

Previous studies have clearly demonstrated strong correlation between in vivo distribution and blood clearance of radiopharmaceuticals for the detection of hypoxia. Present study describes an attempt to improve the in vivo distribution of a previously reported 2-nitroimidazole-(99m)Tc(CO)3 complex by tuning its blood clearance pattern through structural modification of the ligand. Herein, a 2-nitroimidazole-dipicolylamine ligand (2-nitroimidazole-DPA) was synthesized in a two-step procedure and radiolabeled with (99m)Tc(CO)3 core. Subsequently, the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. As intended by its design, 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex was more lipophilic than previously reported 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex (DETA-diethylenetriamine) and showed slower blood clearance. Consequently it showed higher tumor uptake than 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Significantly, despite structural modifications, other parameters such as the tumor to blood ratio and tumor to muscle ratio of the 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex remained comparable to that of 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Present study demonstrates the feasibility of structural modifications for improving in vivo tumor uptake of hypoxia detecting radiopharmaceuticals. This might encourage researchers to improve suboptimal properties of a potential radiopharmaceuticals rather than ignoring it altogether. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

PubMed

León, A; Rey, A; Mallo, L; Pirmettis, I; Papadopoulos, M; León, E; Pagano, M; Manta, E; Incerti, M; Raptopoulou, C; Terzis, A; Chiotellis, E

2002-02-01

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m.

PubMed

Abreu, P R C; Almeida, M C; Bernardo, R M; Bernardo, L C; Brito, L C; Garcia, E A C; Fonseca, A S; Bernardo-Filho, M

2006-06-01

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m ((99m)Tc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with (99m)Tc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with (99m)Tc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with (99m)Tc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with (99m)Tc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract.

Impurities in Tc-99m radiopharmaceutical solution obtained from Mo-100 in cyclotron.

PubMed

Tymiński, Zbigniew; Saganowski, Paweł; Kołakowska, Ewa; Listkowska, Anna; Ziemek, Tomasz; Cacko, Daniel; Dziel, Tomasz

2018-04-01

The gamma emitting impurities in 99m Tc solution obtained from enriched molybdenum 100 Mo metallic target after its irradiation in a cyclotron were measured using a high-purity germanium (HPGe) detector. The radioactivity range of tested samples of 99m Tc was rather low, in the range from 0.34 to 2.39 MBq, thus creating a challenge to investigate the standard measurement HPGe system for impurity detection and quantification. In the process of 99m Tc separation from irradiated target the AnaLig® Tc-02 resin, Dionex H + and Alumina A columns were used. Fractions of eluates from various steps of separation process were taken and measured for radionuclidic purity. The overall measurement sensitivity of gamma emitters in terms of minimum detectable activity (MDA) was found at the level of 14-70Bq with emission lines in range of 36 - 1836keV resulting in impurity content range of 6.7 × 10 -4 to 3.4 × 10 -3 % for 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc 96 Nb, 97 Nb, 99 Mo contaminants and 9.4 × 10 -3 % for 97m Tc. The usefulness of the chosen measurement conditions and the method applied to testing the potential contaminators was proved by reaching satisfactory results of MDAs less than the criteria of impurity concentration of all nuclides specified in the European Pharmacopoeia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Localization of hemorrhage in a recurrent hemothorax using Tc-99m-sulfur colloid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taillefer, R.; Essiambre, R.; Lemieux, R.

1981-05-01

Tc99m-sulfur colloid scintigraphy has proven clinically useful in identifying gastrointestinal hemorrhages. The authors describe a patient with recurrent hemothorax under oral anticoagulation therapy in which Tc-99m-sulfur colloid imaging was used to determine the site of bleeding.

Radiopharmaceutical considerations for using Tc-99m MAA in lung transplant patients.

PubMed

Ponto, James A

2010-01-01

To elucidate radiopharmaceutical considerations for using technetium Tc-99m albumin aggregated (Tc-99m MAA) in lung transplant patients and to establish an appropriate routine dose and preparation procedure. Tertiary care academic hospital during May 2007 to May 2009. Nuclear pharmacist working in nuclear medicine department. Radiopharmaceutical considerations deemed important for the use of Tc-99m MAA in lung transplant patients included radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity. Evaluation of our initial 12-month experience, published literature, and professional practice guidelines provided the basis for establishing an appropriate dose and preparation procedure of Tc-99m MAA for use in lung transplant patients. Radiochemical purity at typical incubation times and image quality in subsequent lung transplant patients imaged during the next 12 months. Based on considerations of radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity, a routine dose consisting of 3 mCi (111 MBq) and 100,000 particles of Tc-99m MAA for planar perfusion lung imaging of adult lung transplant patients was established as reasonable and appropriate. MAA kits were prepared with a more reasonable amount of Tc-99m and yielded high radiochemical purity values in typical incubation times. Images have continued to be of high diagnostic quality. Tc-99m MAA used for lung transplant imaging can be readily prepared with high radiochemical purity to provide a dose of 3 mCi (111 GBq)/100,000 particles, which provides images of high diagnostic quality.

The presence of sodium nitrate in generator eluate decreases the radiochemical purity of 99mTc-sestamibi.

PubMed

Métayé, Thierry; Rosenberg, Thierry; Guilhot, Joëlle; Bouin-Pineau, Marie-Hélène; Perdrisot, Rémy

2012-09-01

A high radiochemical purity (RCP) is recommended for radiopharmaceutical compounds used in the clinical practice of nuclear medicine. However, some preparations of (99m)Tc-sestamibi contain excess impurities (>6%). To understand the origin of these impurities, we investigated the effect of sodium nitrate on the RCP of sestamibi preparations by testing eluates from 3 commercially available (99m)Tc generators. The sestamibi kits (Stamicis) were reconstituted with (99m)Tc eluate from nitrate-containing wet-column (NCWC), nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators. Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was determined using aluminum oxide sheets as the stationary phase and absolute ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine, albumin nanocolloid, and soluble albumin were also tested for their RCP values with eluates from the 3 different (99m)Tc generators. The RCP assessment of (99m)Tc-sestamibi was performed on 127 Stamicis preparations. Significantly lower RCP values were found for Stamicis kits prepared with the NCWC generator than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001) generators. The number of Stamicis preparations with an RCP under 94% was greater with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration of nitrate in NFWC generator eluates significantly decreased the RCP of the Stamicis preparation. In the absence of nitrate in (99m)Tc eluate, no difference was observed between the RCP values of Stamicis kits prepared with the NFWC and NFDC generators. The (99m)Tc impurities generated by nitrates did not modify the quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because these impurities are not in the heart field of view. No other tested (99m)Tc-radiopharmaceutical interfered with nitrates. We recommend using nitrate-free generator eluates in (99m)Tc-sestamibi preparations to improve the product quality and prevent unnecessary exposure of the patient to radiation.

Remote-loading labeling of liposomes with (99m)Tc-BMEDA and its stability evaluation: effects of lipid formulation and pH/chemical gradient.

PubMed

Li, Shihong; Goins, Beth; Phillips, William T; Bao, Ande

2011-03-01

Efficient, convenient, and stable radiolabeling plays a critical role for the monitoring of liposome behavior via either blood sampling, organ distribution, or noninvasive nuclear imaging. The direct labeling of liposome-carrying drugs without any prior modification undoubtedly is convenient and optimal for liposomal drug testing. In this article, we investigated the effect of various lipid formulations and pH/chemical gradients on the radiolabeling efficiency and entrapment stability of technetium-99m ((99m)Tc) remotely loaded into liposomes, using (99m)Tc-N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine ((99m)Tc-BMEDA) complex. The tested liposomes either contained unsaturated lipid or possessed various surface charges. (99m)Tc could be efficiently loaded into various premanufactured liposomes containing either an ammonium sulfate pH, citrate pH, or glutathione (GSH) chemical gradient. (99m)Tc-entrapment stabilities of these liposomes in phosphate-buffered saline (PBS; pH 7.4) buffer at 25°C were mainly dependent on the pH/chemical gradient, but not lipid formulation. Stability sequence was ammonium sulfate pH-gradient>citrate pH-gradient>GSH-gradient. Stabilities of (99m)Tc-liposomes in 50% fetal bovine serum (FBS)/PBS (pH 7.4) buffer at 37°C are dependent on both lipid formulation and pH/chemical gradient. Specifically, (99m)Tc labeling of the ammonium sulfate pH-gradient liposomes were less stable in 50% FBS/PBS than in PBS, whereas noncationic liposomes with citrate pH- or GSH-gradient displayed higher stability, except that anionic citrate pH-gradient liposomes showed no stability difference in these two media. Cationic liposomes aggregated in 50% FBS/PBS, forming a new discrete fraction with larger particle sizes. These in vitro characterization results have indicated the optimism of using (99m)Tc-BMEDA for labeling pH/GSH gradient liposomes without the requirement of modifying lipid formulation for liposomal therapeutic-agent development.

Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of (161)Tb-folate and (177)Lu-folate.

PubMed

Haller, Stephanie; Pellegrini, Giovanni; Vermeulen, Christiaan; van der Meulen, Nicholas P; Köster, Ulli; Bernhardt, Peter; Schibli, Roger; Müller, Cristina

2016-12-01

The radiolanthanide (161)Tb has, in recent years, attracted increasing interest due to its favorable characteristics for medical application. (161)Tb exhibits similar properties to the widely-used therapeutic radionuclide (177)Lu. In contrast to (177)Lu, (161)Tb yields a significant number of short-ranging Auger/conversion electrons (≤50 keV) during its decay process. (161)Tb has been shown to be more effective for tumor therapy than (177)Lu if applied using the same activity. The purpose of this study was to investigate long-term damage to the kidneys after application of (161)Tb-folate and compare it to the renal effects caused by (177)Lu-folate. Renal side effects were investigated in nude mice after the application of different activities of (161)Tb-folate (10, 20, and 30 MBq per mouse) over a period of 8 months. Renal function was monitored by the determination of (99m)Tc-DMSA uptake in the kidneys and by measuring blood urea nitrogen and creatinine levels in the plasma. Histopathological analysis was performed by scoring of the tissue damage observed in HE-stained kidney sections from euthanized mice. Due to the co-emitted Auger/conversion electrons, the mean absorbed renal dose of (161)Tb-folate (3.0 Gy/MBq) was about 24 % higher than that of (177)Lu-folate (2.3 Gy/MBq). After application of (161)Tb-folate, kidney function was reduced in a dose- and time-dependent manner, as indicated by the decreased renal uptake of (99m)Tc-DMSA and the increased levels of blood urea nitrogen and creatinine. Similar results were obtained when (177)Lu-folate was applied at the same activity. Histopathological investigations confirmed comparable renal cortical damage after application of the same activities of (161)Tb-folate and (177)Lu-folate. This was characterized by collapsed tubules and enlarged glomeruli with fibrin deposition in moderately injured kidneys and glomerulosclerosis in severely damaged kidneys. Tb-folate induced dose-dependent radionephropathy over time, but did not result in more severe damage than (177)Lu-folate when applied at the same activity. These data are an indication that Auger/conversion electrons do not exacerbate overall renal damage after application with (161)Tb-folate as compared to (177)Lu-folate, even though they result in an increased dose deposition in the renal tissue. Global toxicity affecting other tissues than kidneys remains to be investigated after (161)Tb-based therapy, however.

Permeability of ferret trachea in vitro to {sup 99m}{Tc}-DTPA and [{sup 14}C]antipyrine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanafi, Z.; Webber, S.E.; Widdicombe, J.G.

1994-09-01

Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of {sup 99m}{Tc}-diethylenetriamine pentaacetic acid ({sup 99m}{Tc}-DTPA; hydrophilic) and [{sup 14}C]antipyrine ([{sup 14}C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either {sup 99m}{Tc}-DTPA or [{sup 14}C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline {sup 99m}{Tc}-DTPA and [{sup 14}C]AP permeability coefficients were - 4.7 {+-} 0.6 (SE) x 10{sup {minus}7} and -2.2 {+-} 0.1 x 10{sup {minus}5} cm/s, respectively. PAF (10 {mu}M) increased permeability tomore » {sup 99m}{Tc}-DTPA to -35.3 {+-} 7.6 x 10{sup {minus}7} cm/s (P < 0.05), but permeability to [{sup 14}C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 {mu}M), phenylephrine (PE, 100 {mu}M), and albuterol (Alb, 100 {mu}M) caused no change in permeability to {sup 99m}{Tc}-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 {mu}M) significantly increased permeability. Abluminal Hist decreased permeability to [{sup 14}C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to {sup 99m}{Tc}-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent. 37 refs., 11 figs., 1 tab.« less

Evaluation of polyethylene glycol coated liposomes labeled with Tc-99m as a blood pool agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, W.T.; Klipper, R.; Goins, B.

1994-05-01

This investigation evaluated Tc-99m liposomes coated with polyethylene glycol (PEG) as a blood pool agent in comparison with Tc-99m liposomes carrying no surface charge (Neutral) and with Tc-99m autologous red cells. Liposomes (135 nm diameter) encapsulating glutathione were labeled with Tc-99m using the lipophilic chelator, HMPAO as previously described. Autologous red cells were labeled using an Ultratag kit. Labeling efficiencies averaged 66%, 52%, and 97% for the PEG liposomes. Neutral liposomes, and red cells, respectively. Rabbits (3-3.5 Kg) were injected IV via ear vein with 2.0 mls of PEG liposomes (2 mCi, 17 mg phospholipid/Kg body weight, n=5). Neutral liposomesmore » (1.3 mCi, 17 mg phospholipid/Kg body weight, n=4), or red cells (2.6 mCi, n=2). Gamma camera images were acquired at 5,22, and 45 minutes, and 2,20,and 44 hours post-injection. Blood samples were obtained at each time point to determine clearance kinetics. Circulation half lives of both Tc-99m liposome formulations were longer than Tc-99m red cells (8 hrs), with the half life of PEG liposomes (35 hrs) 1.6 times longer than Neutral liposomes (22 hrs). In vivo stability of the Tc-99m label was excellent for the liposomes with only 3.5-4% bladder activity at 45 minutes compared to 12% bladder activity for the red cells. Excellent blood pool images were obtained for the PEG liposomes in the rabbit. Heart/liver ratios calculated from region of interest analysis of 45 minutes images were 1.9, 1.5, and 1.7 for PEG liposomes, Neutral liposomes and red cells. This study demonstrates the feasibility of using Tc-99m PEG liposomes to perform gated cardiac blood pool and rapid gastrointestinal bleeding studies.« less

Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mountford, P.J.; Kettle, A.G.; O'Doherty, M.J.

Technetium-99m-HM-PAO (({sup 99m}Tc)HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr {sup 99m}Tc scan could replace the 24-hr {sup 111}In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr {sup 99}Tc-leukocyte scan, the 4-hr {sup 111}In-leukocyte scan, and the 24-hr {sup 111}In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr {sup 99m}Tc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positivemore » in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr {sup 99m}Tc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr {sup 111}In-leukocyte scans. Because of the high incidence of false-positive 4-hr ({sup 99m}Tc)HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr {sup 111}In-leukocyte scans for detecting intraabdominal sepsis, and that serial {sup 99m}Tc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated.« less

Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy.

PubMed

Garai, Ildikó; Barna, Sandor; Nagy, Gabor; Forgacs, Attila

2016-01-01

Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac-curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi-ological and clinical pitfalls, the diagnostic accuracy will improve.

.sup.100Mo compounds as accelerator targets for production of .sup.99mTc

DOEpatents

Richards, Vernal; Lapi, Suzanne

2016-09-20

Methods of synthesizing .sup.100Mo.sub.2C and .sup.99mTcO.sub.4.sup.- are disclosed. Methods of .sup.100Mo.sub.2C generation involve thermally carburizing .sup.100MoO.sub.3. Methods of .sup.99mTcO.sub.4 generation involve proton bombardment of .sup.100Mo.sub.2C in a cyclotron. Yields of .sup.99mTcO.sub.4 can be increased by sintering .sup.100Mo.sub.2C prior to bombardment. The methods also include recycling of .sup.100Mo.sub.2C to form .sup.100MoO.sub.3. SPECT images obtained using .sup.99mTcO.sub.4 generated by the disclosed methods are also presented.

Comparative analysis of hepatopulmonary shunt obtained from pretherapy 99mTc MAA scintigraphy and post-therapy 90Y Bremsstrahlung imaging in 90Y microsphere therapy.

PubMed

Jha, Ashish Kumar A; Zade, Anand A; Rangarajan, Venkatesh; Purandare, Nilendu; Shah, Sneha A; Agrawal, Archi; Kulkarni, Suyash S; Shetty, Nitin

2012-05-01

(99m)Tc macroaggregate albumin (MAA) scintigraphy is routinely used to estimate the hepatopulmonary shunt (HPS) of (90)Y microspheres because of their comparable average particle sizes (20-30 µm). However, the MAA particle size can vary from 10 to 90 µm. Therefore, HPS computed from (99m)Tc MAA scintigraphy may not accurately represent the HPS of (90)Y microspheres. In view of this, the present study was undertaken to investigate the accuracy of (99m)Tc MAA scintigraphy in estimating the HPS of (90)Y microspheres. Nineteen sessions of transarterial radioembolization using (90)Y therasphere were carried out in 17 patients for hepatic malignancies (both primary and secondary). For each session of therapy, a pretherapeutic (99m)Tc MAA scintigraphy and post-therapeutic (90)Y Bremsstrahlung scintigraphy were performed. The HPSs obtained from these images were compared. The mean HPS fractions calculated from the pretherapeutic (99m)Tc MAA study and the post-therapeutic (90)Y Bremsstrahlung images were 4.77 ± 2.81 and 4.52 ± 2.5%, respectively. The coefficient of correlation (r) was 0.96. (99m)Tc MAA scintigraphy accurately predicts the HPS of (90)Y microspheres.

Synthesis and evaluation of (99m)Tc chelate-conjugated bevacizumab.

PubMed

Camacho, Ximena; García, María Fernanda; Calzada, Victoria; Fernández, Marcelo; Porcal, Williams; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2013-03-01

Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model. For this purpose, Bevacizumab was derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl(2).2H(2)O was added to Bevacizumab-HYNIC and radiolabeled with (99m)TcO(4)(-). The radiochemical stability of the radiolabeled antibody was assessed. Biodistribution and scintigraphy imaging were performed in normal CD1 female mice and in spontaneous adenocarcinoma tumor bearing CD1 mice (n = 5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc-HYNIC-Bevacizumab was 1.37 ± 0.51% and 5.33 ± 2.13% at 4 and 24 h postinjection, respectively. Scintigraphy image studies showed tumor selective uptake of (99m)Tc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that (99m)Tc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

PubMed

Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2017-01-17

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P < 0.001). Autoradiography and histochemical staining results were consistent with selective uptake of the radiotracer in the necrotic regions. Among the these tracers, 99m Tc(EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested 99m Tc(EDDA)-HYNIC-2C-rhein emerged as a "hot spot" imaging probe that has a potential for rapid imaging of necrotic myocardium. The necrosis avidity mechanism of 99m Tc(EDDA)-HYNIC-linker-rhein may be due to its interaction with exposed DNA in necrotic tissues.

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation

DOE PAGES

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; ...

2015-12-29

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curvemore » K 1 = F(1–Aexp(–B/F)) for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.« less

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation.

PubMed

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; Yeghiazarians, Yerem; Ellin, Justin; Verdin, Emily; Boyle, Andrew; Seo, Youngho; Botvinick, Elias H; Gullberg, Grant T

2017-02-01

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99m Tc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99m Tc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99m Tc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99m Tc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve [Formula: see text] for K 1 values estimated with 99m Tc-tefrofosmin using SPECT and MBF values estimated with 13 N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13 N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99m Tc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99m Tc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2  = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99m Tc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99m Tc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.

Measurement of absolute myocardial blood flow in humans using dynamic cardiac SPECT and 99mTc-tetrofosmin: Method and validation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares

The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single-photon emission computed tomography (SPECT). Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curvemore » K 1 = F(1–Aexp(–B/F)) for K 1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH 3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH 3 PET. The flow-dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. The estimated flow-extraction parameters for 99mTc-tefrofosmin were found to be A = 0.91 ± 0.11, B = 0.34 ± 0.20 (R 2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44-3.81 mL/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (P < .001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (P = .037). The PS for 99mTc-tefrofosmin was (0.019 ± 0.10)*MBF + (0.32 ± 0.16). Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF.« less

[Simplicity or complexity of the radiopharmaceutical production process in the light of optimization of radiation protection of staff - 99mTc vs. 18F].

PubMed

Wrzesień, Małgorzata

2018-05-22

A radiopharmaceutical is a combination of a non-radioactive compound with a radioactive isotope. Two isotopes: technetium-99m (99mTc) and fluorine-18 (18F) are worth mentioning on the rich list of isotopes which have found numerous medical applications. Their similarity is limited only to the diagnostic area of applicability. The type and the energy of emitted radiation, the half-life and, in particular, the production method demonstrate their diversity. The 99mTc isotope is produced by a short-lived nuclide generator - molybdenum-99 (99Mo)/99mTc, while 18F is resulting from nuclear reaction occurring in a cyclotron. A relatively simple and easy handling of the 99Mo/99mTc generator, compared to the necessary use a cyclotron, seems to favor the principle of optimizing the radiological protection of personnel. The thesis on the effect of automation of both the 18F isotope production and the deoxyglucose labelling process on the optimization of radiological protection of workers compared to manual procedures during handling of radiopharmaceuticals labelled with 99Tc need to be verified. Measurements of personal dose equivalent Hp(0.07) were made in 5 nuclear medicine departments and 2 radiopharmaceuticals production centers. High-sensitivity thermoluminescent detectors (LiF: Mg, Cu, P - MCP-N) were used to determine the doses. Among the activities performed by employees of both 18F-fluorodeoxyglucose (18F-FDG) production centers and nuclear medicine departments, the manual quality control procedures and labelling of radiopharmaceuticals with 99mTc isotope manifest the greatest contribution to the recorded Hp(0.07). The simplicity of obtaining the 99mTc isotope as well as the complex, but fully automated production process of the 18F-FDG radiopharmaceutical optimize the radiation protection of workers, excluding manual procedures labelling with 99mTc or quality control of 18F-FDG. Med Pr 2018;69(3):317–327. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PubMed

Buda, Alessandro; Crivellaro, Cinzia; Elisei, Federica; Di Martino, Giampaolo; Guerra, Luca; De Ponti, Elena; Cuzzocrea, Marco; Giuliani, Daniela; Sina, Federica; Magni, Sonia; Landoni, Claudio; Milani, Rodolfo

2016-07-01

To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

PubMed

Ahmadpour, Sajjad; Noaparast, Zohreh; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-02-19

Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99m Tc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99m Tc using tricine/EDDA co-ligand. The cellular specific binding of 99m Tc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. Radiochemical purity for 99m Tc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (K d ) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99m Tc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99m Tc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. The 99m Tc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

Predictive Value of 99mTc-MAA SPECT for 90Y-Labeled Resin Microsphere Distribution in Radioembolization of Primary and Secondary Hepatic Tumors.

PubMed

Ilhan, Harun; Goritschan, Anna; Paprottka, Philipp; Jakobs, Tobias F; Fendler, Wolfgang P; Todica, Andrei; Bartenstein, Peter; Hacker, Marcus; Haug, Alexander R

2015-11-01

This study analyzed the predictive value of (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) SPECT for (90)Y-labeled resin microsphere therapy (radioembolization) by comparing uptake on pretherapeutic (99m)Tc-MAA SPECT with uptake on posttherapeutic (90)Y-bremsstrahlung SPECT. We included 502 patients (55% male; mean age ± SD, 62 ± 11 y) who underwent radioembolization between 2005 and 2013 because of primary or secondary liver malignancies (colorectal cancer [n = 195, 38.8%], neuroendocrine tumors [n = 77, 15.3%], breast cancer [n = 68, 13.5%], hepatocellular carcinoma [n = 59, 11.8%], cholangiocellular carcinoma [n = 40, 8.0%], or urologic tumors [n = 14, 2.8%]). Manually drawn regions of interest around tumors and adjacent healthy liver tissue for up to 3 lesions per patient on (99m)Tc-MAA and (90)Y-bremsstrahlung scans were used to quantify mean counts per pixel and evaluate the mean tumor-to-background ratio (TBR). Data were given as mean ± SD. Additionally, uptake in lesions on (99m)Tc-MAA and (90)Y-bremsstrahlung scans was graded visually as homogeneously higher than (grade 1), heterogeneously higher than (grade 2), equal to (grade 3), or lower than (grade 4) uptake in normal liver tissue. The Mann-Whitney U test and Spearman correlation were used to evaluate statistically significant differences between (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT. In total, 1,008 lesions were analyzed. Of the 23% (230/1,008) of lesions that had grade 1 uptake on (99m)Tc-MAA SPECT, 81% (186/230) remained grade 1 after radioembolization whereas 16% (37/230) were grade 2. Of the lesions with grade 2 uptake on (99m)Tc-MAA SPECT, 16% had grade 1 uptake and 82% grade 2 uptake after radioembolization. Of the lesions with grade 3 uptake, however, 27% had grade 1 uptake and 47% grade 2 uptake after radioembolization. Even among the lesions with grade 4 uptake on (99m)Tc-MAA SPECT, 21% had grade 1 uptake and 46% grade 2 uptake after radioembolization. The mean TBR on (99m)Tc-MAA and (90)Y-bremsstrahlung SPECT showed a significant, though low, correlation in the total population (r = 0.26; P < 0.001) and in hepatocellular carcinoma (r = 0.4; P < 0.001), cholangiocellular carcinoma (r = 0.3; P < 0.05), breast cancer (r = 0.3; P < 0.001), colorectal cancer (r = 0.2; P < 0.001), and neuroendocrine tumors (r = 0.2; P < 0.01). Although significant for most lesions, the correlation between (99m)Tc-MAA and (90)Y-microsphere mean TBR was low. Classifying uptake into 4 grades revealed that lesions with high uptake on (99m)Tc-MAA SPECT maintain high uptake within radioembolization. More than 60% of lesions with a pretherapeutically lower uptake than in healthy liver tissue, however, showed high uptake within radioembolization. Patients with low tumor uptake on pretherapeutic (99m)Tc-MAA imaging should not be excluded from radioembolization. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The diagnostic value of 99TcM-2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate hypoxia imaging and its evaluation performance for radiotherapy efficacy in non-small-cell lung cancer.

PubMed

Yang, Yongkun; Han, Gaohua; Xu, Wansong

2016-01-01

This study was designated to assess the diagnostic value of 99 Tc M -2-(2-methyl-5-nitro-1 H -imidazol-1-yl) ethyl dihydrogen phosphate ( 99 Tc M -MNLS) hypoxia imaging and its evaluation performance for radiotherapy efficacy in patients with non-small-cell lung cancer (NSCLC). A total of 61 patients with NSCLC were selected for this study. All patients were injected with 99 Tc M -MNLS within 1 week prior to radiotherapy and they were injected with 99 Tc M -MNLS again 3 months after radiotherapy. Qualitative analysis along with semiquantitative analysis results were obtained from hypoxia imaging. Meanwhile, the effect of radiotherapy on patients with NSCLC was evaluated based on the solid tumor curative effect evaluation standard. Finally, SPSS 19.0 statistical software was implemented for statistical analysis. There was no significant difference in age or sex between the NSCLC patient group and benign patient group ( P >0.05). 99 Tc M -MNLS was selectively concentrated in tumor tissues with a clear imaging in 24 hours. Results from both qualitative analysis and semiquantitative analysis indicated that the sensitivity and specificity of 99 Tc M -MNLS hypoxia imaging in diagnosing NSCLC were 93.8% and 84.6% and 72.9% and 100%, respectively. Moreover, the receiver operating characteristic curve provided evidence that 99 Tc M -MNLS hypoxia imaging was a powerful diagnostic tool in distinguishing malignant lung cancer from benign lesions. As suggested by 24-hour imaging, the tumor-to-normal ratio of patients in the 99 Tc M -MNLS high-intake group and low-intake group had a decline of 24.7% and 14.4% after radiotherapy, respectively. The decline in the tumor-to-normal ratio between the two dosage groups was significantly different ( P <0.05). 99 Tc M -MNLS hypoxia imaging had reliable values in both diagnosing NSCLC and evaluating therapeutic effects of radiotherapy on patients with NSCLC.

Bombesin Encapsulated in Long-Circulating pH-Sensitive Liposomes as a Radiotracer for Breast Tumor Identification.

PubMed

De Barros, André Luís Branco; Mota, Luciene Das Graças; Coelho, Marina Melo Antunes; Corrêa, Natássia Caroline Resende; De Góes, Alfredo Miranda; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2015-02-01

Bombesin (BBN) is a tetradecapeptide that binds specifically to gastrin-releasing peptide receptors in humans. These receptors are over-expressed in several forms of cancer; radiolabeled BBN could therefore be used to detect such cancers. However, the degradation of peptides is a critical issue in the development of tumor tracers. Liposomes can be used to overcome this problem and improve the uptake of tracers by tumors. Therefore, the purpose of this study was to prepare and characterize long-circulating and pH-sensitive liposomes (SpHL) containing 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-BBN(7-14). In addition, the ability of this system to identify human breast cancer tissue was evaluated using biodistribution studies and scintigraphic images. Long-circulating and pH-sensitive liposomes (SpHL) were prepared and freeze-dried in the presence of cryoprotectants (glucose, mannitol, and trehalose). They were subsequently reconstituted with a solution of 99mTc-HYNIC-βAla-Bombesin(7-14) (99mTc-BBN(7-14)). The liposomes were evaluated for size, encapsulation percentage, radiotracer leakage, and storage stability. In addition, in vivo studies were performed in breast tumor-bearing nude mice. Liposomes in the presence of glucose (SpHLG), exhibited a mean diameter of 164.5 ± 6.5 nm and exhibited a 99mTc-BBN(7-14) encapsulation percentage of 30%. In addition, they remained highly stable for up to 120 days of storage. SpHLG- 99mTc-BBN(7-14) showed longer blood circulation than free 99mTc-BBN(7-14), did. The tumor-to-muscle and tumor-to-blood ratios for SpHLG-99mTc-BBN(7-14 were high at 4 h post-injection (9.31%ID/g and 7.93%ID/g, respectively). Furthermore, scintigraphic images revealed a strong signal in the tumor area, indicating tumor specificity of SpHLG-99mTc-BBN(7-14). In summary, SpHLG-99mTc-BBN(7-14) presented characteristics suitable for a diagnostic agent, and is a potential tool for tumor identification.

Measurement of Absolute Myocardial Blood Flow in Humans Using Dynamic Cardiac SPECT and 99mTc-tetrofosmin: Method and Validation

PubMed Central

Shrestha, Uttam; Sciammarella, Maria; Alhassen, Fares; Yeghiazarians, Yerem; Ellin, Justin; Verdin, Emily; Boyle, Andrew; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

2015-01-01

Background The objective of this study was to measure myocardial blood flow (MBF) in humans using 99mTc-tetrofosmin and dynamic single photon emission computed tomography (SPECT). Methods Dynamic SPECT using 99mTc-tetrofosmin and dynamic positron emission tomography (PET) was performed on a group of 16 patients. The SPECT data were reconstructed using a 4D-spatiotemporal iterative reconstruction method. The data corresponding to 9 patients were used to determine the flow-extraction curve for 99mTc-tefrofosmin while data from the remaining 7 patients were used for method validation. The nonlinear tracer correction parameters A and B for 99mTc-tefrofosmin were estimated for the 9 patients by fitting the flow-extraction curve K1=F(1−Aexp(−BF)) for K1 values estimated with 99mTc-tefrofosmin using SPECT and MBF values estimated with 13N-NH3 using PET. These parameters were then used to calculate MBF and coronary flow reserve (CFR) in three coronary territories (LAD, RCA, and LCX) using SPECT for an independent cohort of 7 patients. The results were then compared with that estimated with 13N-NH3 PET. The flow dependent permeability surface-area product (PS) for 99mTc-tefrofosmin was also estimated. Results The estimated flow extraction parameters for 99mTc-tefrofosmin was found to be A=0.91±0.11, B=0.34±0.20 (R2 = 0.49). The range of MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). However, the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The PS for 99mTc-tefrofosmin was (0.091 ± 0.10) * MBF = (0.32 ± 0.16). Conclusions Dynamic cardiac SPECT using 99mTc-tetrofosmin and a clinical two-headed SPECT/CT scanner can be a useful tool for estimation of MBF. PMID:26715603

DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy.

PubMed

Rief, Matthias; Hartmann, Lisa; Geisel, Dominik; Richter, Felicitas; Brenner, Winfried; Dewey, Marc

2018-07-01

To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99m Tc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99m Tc activity in blood samples. Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99m Tc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX. The 99m Tc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99m Tc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451). DSB counts reflect 99m Tc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging. • Myocardial perfusion scintigraphy using 99m Tc induces time-dependent double-strand breaks (DSBs) • γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection • Activity measurements of 99m Tc correlate well with detected DSB • DSB foci induced by 99m Tc return to baseline 24h after radiotracer injection.

PET/CT-Based Dosimetry in 90Y-Microsphere Selective Internal Radiation Therapy: Single Cohort Comparison With Pretreatment Planning on (99m)Tc-MAA Imaging and Correlation With Treatment Efficacy.

PubMed

Song, Yoo Sung; Paeng, Jin Chul; Kim, Hyo-Cheol; Chung, Jin Wook; Cheon, Gi Jeong; Chung, June-Key; Lee, Dong Soo; Kang, Keon Wook

2015-06-01

⁹⁰Y PET/CT can be acquired after ⁹⁰Y-microsphere selective radiation internal therapy (SIRT) to describe radioactivity distribution. We performed dosimetry using ⁹⁰Y-microsphere PET/CT data to evaluate treatment efficacy and appropriateness of activity planning from (99m)Tc-MAA scan and SPECT/CT. Twenty-three patients with liver malignancy were included in the study. (99m)Tc-MAA was injected during planning angiography and whole body (99m)Tc-MAA scan and liver SPECT/CT were acquired. After SIRT using ⁹⁰Y-resin microsphere, ⁹⁰Y-microsphere PET/CT was acquired. A partition model (PM) using 4 compartments (tumor, intarget normal liver, out-target normal liver, and lung) was adopted, and absorbed dose to each compartment was calculated based on measurements from (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT, respectively, to be compared with each other. Progression-free survival (PFS) was evaluated in terms of tumor absorbed doses calculated by (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT results. Lung shunt fraction was overestimated on (99m)Tc-MAA scan compared with ⁹⁰Y-microsphere PET/CT (0.060 ± 0.037 vs. 0.018 ± 0.026, P < 0.01). Tumor absorbed dose exhibited a close correlation between the results from (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT (r = 0.64, P < 0.01), although the result from (99m)Tc-MAA SPECT/CT was significantly lower than that from ⁹⁰Y-microsphere PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy, P < 0.01). Absorbed dose to in-target normal liver was overestimated on (99m)Tc-MAA SPECT/CT compared with PET/CT (62.6 ± 38.2 Gy vs. 45.2 ± 32.0 Gy, P = 0.02). Absorbed dose to out-target normal liver did not differ between (99m)Tc-MAA SPECT/CT and ⁹⁰Y-microsphere PET/CT (P = 0.49). Patients with tumor absorbed dose >200 Gy on ⁹⁰Y-microsphere PET/CT had longer PFS than those with tumor absorbed dose ≤200 Gy (286 ± 56 days vs. 92 ± 20 days, P = 0.046). Tumor absorbed dose calculated by (99m)Tc-MAA SPECT/CT was not a significant predictor for PFS. Activity planning based on (99m)Tc-MAA scan and SPECT/CT can be effectively used as a conservative method. Post-SIRT dosimetry based on ⁹⁰Y-microsphere PET/CT is an effective method to predict treatment efficacy.

PET/CT-Based Dosimetry in 90Y-Microsphere Selective Internal Radiation Therapy: Single Cohort Comparison With Pretreatment Planning on 99mTc-MAA Imaging and Correlation With Treatment Efficacy

PubMed Central

Song, Yoo Sung; Paeng, Jin Chul; Kim, Hyo-Cheol; Chung, Jin Wook; Cheon, Gi Jeong; Chung, June-Key; Lee, Dong Soo; Kang, Keon Wook

2015-01-01

Abstract 90Y PET/CT can be acquired after 90Y-microsphere selective radiation internal therapy (SIRT) to describe radioactivity distribution. We performed dosimetry using 90Y-microsphere PET/CT data to evaluate treatment efficacy and appropriateness of activity planning from 99mTc-MAA scan and SPECT/CT. Twenty-three patients with liver malignancy were included in the study. 99mTc-MAA was injected during planning angiography and whole body 99mTc-MAA scan and liver SPECT/CT were acquired. After SIRT using 90Y-resin microsphere, 90Y-microsphere PET/CT was acquired. A partition model (PM) using 4 compartments (tumor, intarget normal liver, out-target normal liver, and lung) was adopted, and absorbed dose to each compartment was calculated based on measurements from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT, respectively, to be compared with each other. Progression-free survival (PFS) was evaluated in terms of tumor absorbed doses calculated by 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT results. Lung shunt fraction was overestimated on 99mTc-MAA scan compared with 90Y-microsphere PET/CT (0.060 ± 0.037 vs. 0.018 ± 0.026, P < 0.01). Tumor absorbed dose exhibited a close correlation between the results from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT (r = 0.64, P < 0.01), although the result from 99mTc-MAA SPECT/CT was significantly lower than that from 90Y-microsphere PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy, P < 0.01). Absorbed dose to in-target normal liver was overestimated on 99mTc-MAA SPECT/CT compared with PET/CT (62.6 ± 38.2 Gy vs. 45.2 ± 32.0 Gy, P = 0.02). Absorbed dose to out-target normal liver did not differ between 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT (P = 0.49). Patients with tumor absorbed dose >200 Gy on 90Y-microsphere PET/CT had longer PFS than those with tumor absorbed dose ≤200 Gy (286 ± 56 days vs. 92 ± 20 days, P = 0.046). Tumor absorbed dose calculated by 99mTc-MAA SPECT/CT was not a significant predictor for PFS. Activity planning based on 99mTc-MAA scan and SPECT/CT can be effectively used as a conservative method. Post-SIRT dosimetry based on 90Y-microsphere PET/CT is an effective method to predict treatment efficacy. PMID:26061323

⁹⁹mTc/Re complexes bearing bisnitroimidazole or mononitroimidazole as potential bioreductive markers for tumor: synthesis, physicochemical characterization and biological evaluation.

PubMed

Mei, Lei; Wang, Yue; Chu, Taiwei

2012-12-01

Four monoamine-monoamide dithiol (MAMA) ligands containing two or one nitroimidazole moieties were synthesized and labeled with (99m)Tc (labeling yield > 95%). The proposed structures of (99m)Tc-complexes are identified by comparison with analogous Re-MAMA complexes. (99m)Tc-MAMA complexes show better physicochemical characters than (99m)TcO-(PnAO-1-(2-nitroimidazole)). Reduction potentials of nitro groups of the rhenium complexes are within the range for bioreductive compounds. As expected, biodistribution studies demonstrate that the 2-nitroimidazole complex shows better tumor-to-tissue ratios than 4-nitroimidazole analog for mononitroimidazole complexes, but not for MAMA-bisnitroimidazoles due to higher lipophilicity. Both the bisnitroimidazole compounds show rapider excretion, lower background activity in liver and higher tumor-to-tissue ratios than the mononitroimidazoles. Better biodistribution characteristic makes both the MAMA-bisnitroimidazole complexes, especially (99m)Tc-15, be potential tumor hypoxia marker. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Preoperative diagnosis of orbital cavernous hemangioma: a 99mTc-RBC SPECT study.

PubMed

Burroni, Luca; Borsari, Giulia; Pichierri, Patrizia; Polito, Ennio; Toscano, Olga; Grassetto, Gaia; Al-Nahhas, Adil; Rubello, Domenico; Vattimo, Angelo Giuseppe

2012-11-01

This study aimed to describe 99mTc-labeled RBC scintigraphy as a diagnostic method for orbital cavernous hemangiomas and to evaluate this diagnostic tool according to surgical outcomes. Fifty-five patients with clinical and radiological (US, CT, and/or MRI) suspicion of unilateral cavernous hemangioma of the orbit underwent 99mTc-RBC SPECT study.Qualitative and semiquantitative evaluations were performed, and results were statistically analyzed. SPECT images showed focal uptake in the orbital mass in 36 of 55 patients. Nineteen patients had a negative scintigraphic pattern, with concordance of early and late absence of uptake of 99mTc-RBC.Our procedure showed 100% sensitivity and 88.9% specificity for the diagnosis of orbital cavernous hemangioma, with a positive predictive value of 90.9% and a negative predictive value of 100%. 99mTc-RBC imaging is safe, easy to perform, and highly accurate in providing adequate clinical and surgical management. As a noninvasive and highly specific method for diagnosing orbital hemangioma, 99mTc-RBC scintigraphy can avoid more invasive imaging or biopsy.

Use of 99mTc-Tilmanocept as a Single Agent for Sentinel Lymph Node Identification in Breast Cancer: A Retrospective Pilot Study.

PubMed

Unkart, Jonathan T; Wallace, Anne M

2017-09-01

99m Tc-tilmanocept received recent Food and Drug Administration approval for lymphatic mapping in 2013. However, to our knowledge, no prior studies have evaluated the use of 99m Tc-tilmanocept as a single agent in sentinel lymph node (SLN) biopsy in breast cancer. Methods: We executed this retrospective pilot study to assess the ability of 99m Tc-tilmanocept to identify sentinel nodes as a single agent in clinically node-negative breast cancer patients. Patients received a single intradermal injection overlying the tumor of either 18.5 MBq (0.5 mCi) of 99m Tc-tilmanocept on the day of surgery or 74.0 MBq (2.0 mCi) on the day before surgery by a radiologist. Immediate 3-view lymphoscintigraphy was performed. Intraoperatively, SLNs were identified with a portable γ-probe. A node was classified as hot if the count (per second) of the node was more than 3 times the background count. Descriptive statistics are reported. Results: Nineteen patients underwent SLN biopsy with single-agent 99m Tc-tilmanocept. Immediate lymphoscintigraphy identified at least 1 sentinel node in 13 of 17 patients (76.5%). Intraoperatively, at least 1 (mean, 1.7 ± 0.8; range, 1-3) hot node was identified in all patients. Three patients (15.8%) had 1 disease-positive SLN. Conclusion: In this small, retrospective pilot study, 99m Tc-tilmanocept performed well as a single agent for intraoperative sentinel node identification in breast cancer. A larger, randomized clinical trial is warranted to compare 99m Tc-tilmanocept as a single agent with other radiopharmaceuticals for sentinel node identification in breast cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m*

PubMed Central

Abreu, P.R.C.; Almeida, M.C.; Bernardo, R.M.; Bernardo, L.C.; Brito, L.C.; Garcia, E.A.C.; Fonseca, A.S.; Bernardo-Filho, M.

2006-01-01

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m (99mTc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with 99mTc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with 99mTc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with 99mTc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with 99mTc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract. PMID:16691636

The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer.

PubMed

Ozdemir, Didem; Cuhaci, Fatma N; Ozdemir, Elif; Aydin, Cevdet; Ersoy, Reyhan; Turkolmez, Seyda; Cakir, Bekir

2016-06-01

Surgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. DTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6-9 months after RAI. There were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11±12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. Postoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients.

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

PubMed

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

Development of medicine-intended isotope production technologies at Yerevan Physics Institute

NASA Astrophysics Data System (ADS)

Avetisyan, Albert; Avagyan, Robert; Kerobyan, Ivetta; Dallakyan, Ruben; Harutyunyan, Gevorg; Melkonyan, Aleksandr

2015-05-01

Accelerator-based 99mTc and 123I isotopes production technologies were created and developed at A.Alikhanyan National Science Laboratory (former Yerevan Physics Institute - YerPhI). The method involves the irradiation of natural molybdenum (for 99mTc production) and natural xenon (for 123I production) using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the YerPhI. We have developed and tested the extraction of 99mTc and 123I from the irradiated natural MoO3 and natural Xe, respectively. The production method has been developed and shown to be successful. The current activity is devoted to creation and development of the technology of direct production 99mTc on the 100Mo as target materials using the proton beam from an IBA C18/18 cyclotron. The proton cyclotron C18/18 (producer - IBA, Belgium) was purchased and will be installed nearby AANL (YerPhI) till end 2014. The 18 MeV protons will be used to investigate accelerator-based schemes for the direct production of 99mTc. Main topics of studies will include experimental measurement of 99mTc production yield for different energies of protons, irradiation times, intensities, development of new methods of 99mTc extraction from irradiated materials, development of target preparation technology, development of target material recovery methods for multiple use and others.

Media Fill Test for validation of autologous leukocytes separation and labelling by (99m)Tc-HmPAO.

PubMed

Urbano, Nicoletta; Modoni, Sergio; Schillaci, Orazio

2013-01-01

Manufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with (99m)Tc-exametazime ((99m)Tc-hexamethylpropyleneamine oxime; (99m)Tc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with (99m)Tc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas (99m)Tc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test. The study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth. No evidence of turbidity was observed in all the steps assayed by the Media Fill. In the separation and labelling of autologous leukocytes with (99m)Tc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification of Warthin tumor: magnetic resonance imaging versus salivary scintigraphy with technetium-99m pertechnetate.

PubMed

Motoori, Ken; Ueda, Takuya; Uchida, Yoshitaka; Chazono, Hideaki; Suzuki, Homare; Ito, Hisao

2005-01-01

The aim of this study was to evaluate the accuracy of technetium-99m (Tc-99m) pertechnetate scintigraphy and magnetic resonance (MR) imaging in the diagnosis of Warthin tumor. Sixteen cases of Warthin tumor and 17 cases of non-Warthin tumor were examined by Tc-99m pertechnetate scintigraphy with lemon juice stimulation and MR imaging, including T1-weighted, T2-weighted, short inversion time inversion recovery, diffusion-weighted, and contrast-enhanced dynamic images. We used the receiver operating characteristic (ROC) curve to evaluate diagnostic accuracy. The mean area under the ROC curves of MR imaging in the diagnosis of Warthin tumor (0.97) was higher than that of Tc-99m pertechnetate scintigraphy (0.88). Magnetic resonance imaging is more useful in the evaluation of Warthin tumor than Tc-99m pertechnetate scintigraphy.

Symptomatic urinary tract infection in preschool Australian children.

PubMed

Craig, J C; Irwig, L M; Knight, J F; Sureshkumar, P; Roy, L P

1998-04-01

To describe the demographic and clinical features, short-term outcomes, microbiology and renal tract abnormalities of a cohort of young Australian children with symptomatic urinary tract infection. A total of 304 children < 5 years with their first documented symptomatic urinary tract infection who presented consecutively to the Emergency Department of a paediatric hospital between March 1993 and December 1994 and without a known predisposing cause were identified and details of their acute illness were recorded. Renal tract sonography, micturating cystourethrography and Tc-99 m dimercaptosuccinic acid scintigraphy (DMSA) were routinely performed. Of those who presented with urinary tract infection, 169 were boys and 135 girls; 64% were less than 1 year of age. For children from the local community, the cumulative incidence of urinary tract infection within the first 5 years of life was estimated to be 1.9% for boys and 1.8% for girls. There were no significant differences in illness characteristics according to mode of referral or geographical locality. Presenting symptoms were generally nonspecific and not referrable to the urinary tract. There were no deaths. One per cent of children required ventilatory support, and bacteraemia occurred in 6%, all of whom were under 6 months of age. E. coli was the causal organism in 84%, and a high in vitro resistance to ampicillin/ amoxycillin (54%) was demonstrated by the pathogens isolated. Bacteriuria was eradicated in 99% with antimicrobial treatment. In this setting, the sensitivities of dipstick urinalysis (leucocyte esterase+/-nitrites) and pyuria on microscopy (>10 x 10(6) white cells L(-1)) were 85%. Abnormal DMSA scintigraphy was detected in 39%, vesicoureteric reflux in 28%, and obstructive uropathy in 1%. This study provides current and local data on a large sample of children <5 years with urinary tract infection, which are useful to clinicians who manage children at risk of the condition.

Production of radionuclide molybdenum 99 in a distributed and in situ fashion

DOEpatents

Gentile, Charles A.; Cohen, Adam B.; Ascione, George

2016-04-19

A method and apparatus for producing Mo-99 from Mo-100 for the use of the produced Mo-99 in a Tc-99m generator without the use of uranium is presented. Both the method and apparatus employ high energy gamma rays for the transformation of Mo-100 to Mo-99. The high energy gamma rays are produced by exposing a metal target to a moderated neutron output of between 6 MeV and 14 MeV. The resulting Mo-99 spontaneously decays into Tc-99m and can therefore be used in a Tc-99m generator.

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors.

PubMed

Trogrlic, Mate; Tezak, Stanko

2016-01-01

Aim of this study was to determine the value of technetium-99m-hydrazinonicotinyl-Tyr3-octreotide (99mTc-ED-DA/HYNIC-TOC) in patients with somatostatin receptor (SSR) positive tumors of head and neck region. A total number of 16 patients were enrolled in this study. Planar whole body (WB) and single photon emission computed tomography (SPECT) images were acquired at 2 and 4 hours after the injection of approximately 670 MBq of 99mTc-EDDA/HYNIC-TOC. Additional single photon emission computed tomography/computed tomography (SPECT/CT) images of the head and neck region were acquired at 4h post tracer injection. Clinical and imaging follow up were taken as the reference standard. There were 10 female and 6 male patients of age 57.7 ± 12.9 years (58.5; 32-78) years. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy (SRS) was TP in 13 patients, TN in two and FP in one. Follow up period for SRS was 31.1 ± 19.4 (29; 2-63) months. 99mTc-EDDA/HYNIC-TOC scintigraphy provided additional information in 50% of patients, with impact on patient management in the same percentage of patients. Distant metastases were found in nine out of 16 patients (56%). 99mTc-EDDA/HYNIC-TOC SRS had sensitivity of 100% (75.3-100%), specificity of 66.7% (9.4-99.2%), accuracy of 93.7%, positive predictive value of 92.9% (66.1-99.8%), and negative predictive value of 100% (15.8-100%). Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC is very useful imaging method in the evalu-ation of patients with SSR positive tumors of head and neck region.

Examination of Technetium Transport Through Soils Under Contrasting Redox Conditions: Batch and Column Work

NASA Astrophysics Data System (ADS)

Dozier, R.; Montgomery, D.; Wylie, E. M.; Dogan, M.; Moysey, S. M.; Powell, B. A.; Martinez, N. E.

2015-12-01

Experiments were performed under various reducing conditions to evaluate the transport behavior of technetium-99 (99Tc) in the presence of sandy clay loam soil from the Savannah River Site (SRS) and goethite, magnetite, and iron sulfide, which were selected for their increasing reducing potential. The experiments were conducted to investigate how redox reaction equilibria and rates affect the overall mobility of 99Tc as it transitions between the mobile Tc(VII) and immobile Tc(IV). Under oxygen-rich conditions, batch sorption isotherms measured for TcO4- across the concentration range 0.5 to 50 μg/L were linear with distribution coefficients (Kd) of 0.78 mL/g or lower, with decreasing sorption for goethite, magnetite, and iron sulfide, respectively. Addition of Na2S resulted in a marked increase in apparent 99Tc sorption to the solid phase, with Kd of 43 mL/g, 35 mL/g, and 29 mL/g, following the same mineral trend as previously. The increased Kd values are possibly due to reduction of Tc(VII) to Tc(IV), resulting in the formation of TcO2(s). SRS soil batch sorption isotherms measured for TcO4- across the same concentration range were also linear, with Kd of 0.7 mL/g for unadjusted pH, 5.1 mL/g for pH of around 6, and 6.7 mL/g for pH of around 4. Kinetic batch sorption tests showed less than 10% 99Tc sorption in an oxidizing environment and greater than 95% sorption in a reducing environment, with both reactions occurring on the order of minutes. In contrast, desorption experiments initiated by transferring the samples from a reducing environment (0.1% H2(g)/99.9% N2(g)) to atmospheric conditions resulted in a slow desorption step on the order of days. Column experiments conducted with the SRS sands indicate a retardation factor of 1.17 for 99Tc under oxygen rich conditions. Additional column experiments are being conducted to evaluate 99Tc transport dependencies on transitions between oxygen rich and poor conditions.

Urinary tract infection in small children: the evolution of renal damage over time.

PubMed

Swerkersson, Svante; Jodal, Ulf; Sixt, Rune; Stokland, Eira; Hansson, Sverker

2017-10-01

Our objective was to analyze the evolution of kidney damage over time in small children with urinary tract infection (UTI) and factors associated with progression of renal damage. From a cohort of 1003 children <2 years of age with first-time UTI, a retrospective analysis of 103 children was done. Children were selected because of renal damage at index 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy at least 3 months after UTI, and a late DMSA scan was performed after at least 2 years. Damage was classified as progression when there was a decline in differential renal function (DRF) by ≥4%, as regression when there was complete or partial resolution of uptake defects. Of 103 children, 20 showed progression, 20 regression, and 63 remained unchanged. There were no differences between groups regarding gender or age. In the progression group, 16/20 (80%) children had vesicoureteral reflux (VUR) grade III-V and 13 (65%) had recurrent UTI. In multivariable regression analysis, both VUR grade III-V and recurrent UTI were associated with progression. In the regression group, 16/20 (80%) had no VUR or grade I-II, and two (10%) had recurrent UTI. Most small children with febrile UTI do not develop renal damage and if they do the majority remain unchanged or regress over time. However, up to one-fifth of children with renal damage diagnosed after UTI are at risk of renal deterioration. These children are characterized by the presence of VUR grades III-V and recurrent febrile UTI and may benefit from follow-up.

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.

Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normalmore » and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.« less

Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

2016-06-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

2016-08-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

(99m)Tc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging.

PubMed

García, María Fernanda; Zhang, Xiuli; Shah, Manankumar; Newton-Northup, Jessica; Cabral, Pablo; Cerecetto, Hugo; Quinn, Thomas

2016-03-15

Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis.

PubMed

Einstein, Andrew J; Shuryak, Igor; Castaño, Adam; Mintz, Akiva; Maurer, Mathew S; Bokhari, Sabahat

2018-05-30

Increasing recognition that transthyretin cardiac amyloidosis (ATTR-CA) is much more common than previously appreciated and the emergence of novel disease-modifying therapeutic agents have led to a paradigm shift in which ATTR-CA screening is considered in high-risk populations, such as patients with heart failure with preserved ejection fraction (HFpEF) or aortic stenosis. Radiation risk from 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy, a test with very high sensitivity and specificity for ATTR-CA, has not been previously determined. Radiation doses to individual organs from 99m Tc-PYP were estimated using models developed by the Medical Internal Radiation Dose Committee and the International Commission on Radiological Protection. Excess future cancer risks were estimated from organ doses, using risk projection models developed by the National Academies and extended by the National Cancer Institute. Excess future risks were estimated for men and women aged 40-80 and compared to total (excess plus baseline) future risks. All-organ excess cancer risks (90% uncertainty intervals) ranged from 5.88 (2.45,11.4) to 12.2 (4.11,26.0) cases per 100,000 patients undergoing 99m Tc-PYP testing, were similar for men and women, and decreased with increasing age at testing. Cancer risks were highest to the urinary bladder, and bladder risk varied nearly twofold depending on which model was used. Excess 99m Tc-PYP-related cancers constituted < 1% of total future cancers to the critical organs. Very low cancer risks associated with 99m Tc-PYP testing suggest a favorable benefit-risk profile for 99m Tc-PYP as a screening test for ATTR-CA in high-risk populations, such as such as patients with HFpEF or aortic stenosis.

The utility of two somatostatin analog radiopharmaceuticals in assessment of radiologically indeterminate pulmonary lesions.

PubMed

Sobic-Saranovic, Dragana P; Pavlovic, Smiljana V; Artiko, Vera M; Saranovic, Djordjije Z; Jaksic, Emilija D; Subotic, Dragan; Nagorni-Obradovic, Ljudmila; Kozarevic, Nebojsa; Petrovic, Nebojsa; Grozdic, Isidora T; Obradovic, Vladimir B

2012-01-01

The aim of our study was to assess diagnostic accuracy of Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC scintigraphy for evaluation of pulmonary lesions that appeared ambiguous on computed tomography (CT). Forty-nine consecutive patients (37 men and 12 women; mean age, 60 ± 11 years) with 60 pulmonary lesions on chest radiography and CT were referred for nuclear imaging. They were prospectively allocated to undergo whole-body scintigraphy (WBS) and single photon emission computed tomography (SPECT) using either Tc-99m depreotide (26 patients, group 1) or Tc-99m-EDDA/HYNIC-TOC imaging (23 patients, group 2). Histologic findings after tissue biopsy served as a gold standard for determining diagnostic accuracy of the 2 somatostatin analogs. Visual assessment was complemented by semiquantitative analysis based on target to background ratio. Among the 32 pulmonary lesions scanned with Tc-99m depreotide, focal uptake was increased in 22 of 25 malignancies, whereas no uptake was found in 6 of 7 benign lesions (88% sensitivity, 85% specificity, and 88% accuracy) on both WBS and SPECT. Imaging of 28 pulmonary lesions with Tc-99m-EDDA/HYNIC-TOC had a similar diagnostic yield (sensitivity 87%, specificity 84%, and accuracy 86%). Overall, target to background ratios were higher on SPECT than WBS but not significantly different between groups 1 and 2 (SPECT 2.72 ± 0.70 vs. 2.71 ± 0.50, WBS 1.61 ± 0.32 vs. 1.62 ± 0.28, respectively). This study demonstrates that Tc-99m depreotide and Tc-99m-EDDA/HYNIC-TOC have similar diagnostic value for characterizing pulmonary lesions that appear ambiguous on CT.

Influence of proton-pump inhibitors on stomach wall uptake of 99mTc-tetrofosmin in cadmium-zinc-telluride SPECT myocardial perfusion imaging.

PubMed

Mouden, Mohamed; Rijkee, Karlijn S; Schreuder, Nanno; Timmer, Jorik R; Jager, Pieter L

2015-02-01

Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms. Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups. Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.

Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

PubMed

Chen, Fei; Shao, Kejing; Zhu, Bao; Jiang, Mengjun

2016-05-15

A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro.

PubMed

Lai, Kunbei; Xu, Li; Jin, Chenjin; Wu, Kaili; Tian, Zhen; Huang, Chuangxin; Zhong, Xiaojing; Ye, Haiyun

2011-07-29

To investigate the effects of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms. C57BL/6J mice were used to induce CNV by laser photocoagulation. (99)Tc-MDP at the doses of 0.5 × 10(-1), 1 × 10(-1), and 2 × 10(-1) μg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of (99)Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of (99)Tc-MDP was evaluated in vivo and in vitro. Areas of CNV were significantly suppressed by (99)Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: (99)Tc-MDP treatment of 0.5 × 10(-1) μg/kg (5698.60 ± 1037.70 μm(2)), 1 × 10(-1) μg/kg (3678.34 ± 1328.18 μm(2)), and 2 × 10(-1) μg/kg (2365.78 ± 923.80 μm(2)) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 μm(2); P < 0.001). (99)Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. (99)Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells. Anti-inflammatory treatment with (99)Tc-MDP has therapeutic potential for CNV-related diseases.

Diversification in the Supply Chain of (99)Mo Ensures a Future for (99m)Tc.

PubMed

Cutler, Cathy S; Schwarz, Sally W

2014-07-01

The uncertain availability of (99m)Tc has become a concern for nuclear medicine departments across the globe. An issue for the United States is that currently it is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by production outside the United States. Since the United States uses half the world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced if a producer were located within the United States. The fragility of the old (99)Mo supply chain is being addressed as new facilities are constructed and new processes are developed to produce (99)Mo without highly enriched uranium. The conversion to low-enriched uranium is necessary to minimize the potential misuse of highly enriched uranium in the world for nonpeaceful means. New production facilities, new methods for the production of (99)Mo, and a new generator elution system for the supply of (99m)Tc are currently being pursued. The progress made in all these areas will be discussed, as they all highlight the need to embrace diversity to ensure that we have a robust and reliable supply of (99m)Tc in the future. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Synthesis and biological evaluation of (99m)Tc-DMP-NGA as a novel hepatic asialoglycoprotein receptor imaging agent.

PubMed

Yang, Wenjiang; Mou, Tiantian; Zhang, Xianzhong; Wang, Xuebin

2010-01-01

A novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared by coupling the SATP with galactosyl-neoglycoalbumin (NGA). The DMP-NGA was labeled with technetium-99m, and the radiochemical purity in excess of 98% after purified with HPLC. In vivo biodistribution showed that (99m)Tc-DMP-NGA had very high initial liver uptake with good retention. The liver accumulated 99.35+/-9.77%, 74.25+/-3.03%, 52.47+/-7.58% of the injected dose per gram at 5, 30 and 120min after injection, respectively. It had relative higher initial liver uptake and much lower blood uptake than that of (99m)Tc-GSA. The liver/blood ratio reached 83.4 at 30min post-injection, while the ratio of liver/kidney was 14.4. The uptakes in other organs in the abdomen were also slightly low. In addition, the hepatic uptake of (99m)Tc-DMP-NGA was blocked by preinjecting free GSA as blocking agent. The result indicates that (99m)Tc-DMP-NGA has specific binding to ASGP receptor. Images acquired with Kodak In-Vivo Imaging System FX Pro showed significant difference before and after inhibition. The promising biological properties of (99m)Tc-DMP-NGA afford potential applications in liver receptor imaging for assessment of hepatocyte function.

/sup 99m/Tc-IDA imaging in the differential diagnosis of acute cholecystitis and acute pancreatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonseca, C.; Greenberg, D.; Rosenthall, L.

1979-02-01

Technetium-/sup 99m/-labelled dimethly-acetanilide-iminodiacetic acid (/sup 99m/Tc-IDA) hepato-biliary imaging was evaluated for its efficacy in distinguishing acute cholecystitis from acute pancreatitis. In a retrospective review, gallbladders were demonstrated by /sup 99m/Tc-IDA in 13 of 15 patients (87%) with acute pancreatitis. This is significantly higher than reports on the frequency of gallbladder filling with oral and intravenous cholangiography in the presence of acute cholecystitis.

Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: comparison with ultrasound and 99mTc-sestamibi scans.

PubMed

Argirò, Renato; Diacinti, Daniele; Sacconi, Beatrice; Iannarelli, Angelo; Diacinti, Davide; Cipriani, Cristiana; Pisani, Daniela; Romagnoli, Elisabetta; Biffoni, Marco; Di Gioia, Cira; Pepe, Jessica; Bezzi, Mario; Letizia, Claudio; Minisola, Salvatore; Catalano, Carlo

2018-05-07

To evaluate the diagnostic performance of 3TMRI in comparison with ultrasound (US) and 99mTc-sestamibi scan for presurgical localisation of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT). Fifty-seven patients affected by PHPT were prospectively enrolled and underwent US, 99mTc-sestamibi and 3TMRI. T2-weighted and post-contrast T1-weighted Iterative decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) sequences were acquired. Diagnostic performance of US, 99mTc-sestamibi and MRI in localising PTAs to correct quadrant were compared according to surgical and pathological findings. According to surgical findings, US correctly localised 41/46 PTAs (sensitivity of 89.1%; specificity 97.5%; PPV 93.1% and NPV 95.6%); 99mTc-sestamibi correctly localised 38/46 PTAs (sensitivity 83.6%, specificity 98.3%, PPV 95% and NPV 93.7%). US and 99mTc-sestamibi combined had a sensitivity of 93.4% (43/46 PTAs), specificity of 98.3%, PPV 95% and NPV 98.3%. MRI correctly localised 45/46 PTAs (sensitivity 97.8%; specificity 97.5%; PPV 93.7% and NPV 99.2%). MRI was able to detect six adenomas missed by 99mTc-sestamibi and two adenomas missed by US. MRI and US were able to detect all enlarged parathyroid glands in patients with multiglandular disease. MRI identified six of seven ectopic adenomas. Our study demonstrated high diagnostic performance of 3T MRI in the preoperative PTAs quadrant localisation, as well as in patients with multiglandular disease and ectopic PTAs. MRI may be preferred to adequately select patient candidates for minimally invasive parathyroidectomy (MIP). • PTA(s) quadrant localisation by 3TMRI was more accurate than US+99mTc-sestamibi. • MRI identified all enlarged glands in multiglandular disease similarly to US. • MRI identified 6/7 ectopic PTAs similarly to 99mTc-sestamibi. • Presurgical PTA(s) localisation by 3TMRI select the optimal candidates for MIP.

Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans.

PubMed

de Assis, Danielle Nogueira; Araújo, Raquel Silva; Fuscaldi, Leonardo Lima; Fernandes, Simone Odília Antunes; Mosqueira, Vanessa Carla Furtado; Cardoso, Valbert Nascimento

2018-03-01

Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99m Tc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection. Fluconazole was radiolabeled with technetium-99 metastable ( 99m Tc) and encapsulated into conventional ( 99m Tc-Fluconazole-PLA-POLOX) and surface-modified ( 99m Tc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99m Tc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter. The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99m Tc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99m Tc-fluconazole, but the results did not show a significant difference between NC formulations. These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99m Tc-fluconazole at this site. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Synthesis, Characterization, and Initial Biological Evaluation of [99m Tc]Tc-Tricarbonyl-labeled DPA-α-MSH Peptide Derivatives for Potential Melanoma Imaging.

PubMed

Gao, Feng; Sihver, Wiebke; Bergmann, Ralf; Belter, Birgit; Bolzati, Cristina; Salvarese, Nicola; Steinbach, Jörg; Pietzsch, Jens; Pietzsch, Hans-Jürgen

2018-06-06

α-Melanocyte stimulating hormone (α-MSH) derivatives target the melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the α-MSH-derived peptide NAP-NS1 (Nle-Asp-His-d-Phe-Arg-Trp-Gly-NH 2 ) with and without linkers was conjugated with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (DPA-COOH) and labeled with [ 99m Tc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pot method, while obtaining similarly high yields. Negligible trans-chelation and high stability in physiological solutions was determined for the [ 99m Tc]Tc-tricarbonyl-peptide conjugates. Coupling an ethylene glycol (EG)-based linker increased the hydrophilicity. The peptide derivatives displayed high binding affinity in murine B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell homogenates. Preliminary in vivo studies with one of the [ 99m Tc]Tc-tricarbonyl-peptide conjugates showed good stability in blood and both renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insight into the potential relevance of the 99m Tc-labeled peptides for in vivo imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcification.

PubMed

Bordoloi, Jayanta Kumar; Berry, David; Khan, Irfan Ullah; Sunassee, Kavitha; de Rosales, Rafael Torres Martin; Shanahan, Catherine; Blower, Philip J

2015-03-21

The first (99m)Tc and (188)Re complexes containing two pendant bisphosphonate groups have been synthesised, based on the mononuclear M(v) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the (99)Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The (99m)Tc complex showed greater affinity for synthetic and biological hydroxyapatite, and greater stability in biological media, than the well-known but poorly-characterised and inhomogeneous bone imaging agent (99m)Tc-MDP. It gave excellent SPECT images of both bone calcification (mice and rats) and vascular calcification (rat model), but the improved stability and the availability of two pendant bisphosphonate groups conferred no dramatic advantage in imaging over the conventional (99m)Tc-MDP agent in which the bisphosphonate group is bound directly to Tc. The (188)Re complex also showed preferential uptake in bone. These tracers and the biological model of vascular calcification offer the opportunity to study the biological interpretation and clinical potential of radionuclide imaging of vascular calcification and to deliver radionuclide therapy to bone metastases.

Relationship between quantitative and descriptive methods of studying blood flow through intrapulmonary arteriovenous anastomoses during exercise.

PubMed

Duke, Joseph W; Elliott, Jonathan E; Laurie, Steven S; Voelkel, Thomas; Gladstone, Igor M; Fish, Mathews B; Lovering, Andrew T

2017-09-01

Several methods exist to study intrapulmonary arteriovenous anastomoses (IPAVA) in humans. Transthoracic saline contrast echocardiography (TTSCE), i.e., bubble scores, is minimally-invasive, but cannot be used to quantify the magnitude of blood flow through IPAVA (Q IPAVA ). Radiolabeled macroaggregates of albumin ( 99m Tc-MAA) have been used to quantify Q IPAVA in humans, but this requires injection of radioactive particles. Previous work has shown agreement between 99m Tc-MAA and TTSCE, but this has not been tested simultaneously in the same group of subjects. Thus, the purpose of this study was to determine if there was a relationship between Q IPAVA quantified with 99m Tc-MAA and bubble scores obtained with TTSCE. To test this, we used 99m Tc-MAA and TTSCE to quantify and detect Q IPAVA at rest and during exercise in humans. Q IPAVA significantly increased from rest to exercise using 99m Tc-MAA and TTSCE and there was a moderately-strong, but significant relationship between methods. Our data suggest that high bubble scores generally correspond with large Q IPAVA quantified with 99m Tc-MAA during exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

PubMed

Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

2015-07-01

This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved kit formulation for preparation of (99m)Tc-HYNIC-TOC: results of preliminary clinical evaluation in imaging patients with neuroendocrine tumors.

PubMed

Korde, Aruna; Mallia, Madhava; Shinto, Ajit; Sarma, H D; Samuel, Grace; Banerjee, Sharmila

2014-11-01

(99m)Tc-HYNIC-TOC is a cost-effective and logistically viable agent for scintigraphy of neuroendocrine tumors overexpressing somatostatin receptors as compared with [(111)In-DTPA-D-Phe(1)] Octreotide (Octreoscan(®)). Several studies have been reported, wherein the efficacy of this agent is demonstrated. In the present article, the authors report the preparation of a single-vial HYNIC-TOC kit suitable for the preparation of 4-5 patient doses (15 mCi/patient) of (99m)Tc-HYNIC-TOC. The kits were tested for sterility and bacterial endotoxins to assure safety of the product. A significant modification in this kit is the inclusion of buffer in the kit itself, unlike in commercially available kits where the buffer solution has to be added during preparation. (99m)Tc-HYNIC-TOC was prepared by adding 20-80 mCi (740-2960 MBq) of freshly eluted Na(99m)TcO4 in 1-3 mL of sterile saline directly into the kit vial and heating the vial in a water bath at 100°C for 20 minutes. The labeling yield and radiochemical purity of (99m)Tc-HYNIC-TOC, prepared using the lyophilized cold kit, were consistently >90%. The kits were evaluated over a period of 9 months and found to be stable when stored at -20°C. Limited clinical studies performed with the (99m)Tc-HYNIC-TOC, formulated using the kit, showed adequate sensitivity and specificity for the detection of gasteroenteropancreatic neuroendocrine tumors.

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

PubMed

Fonti, R; Del Vecchio, S; Zannetti, A; De Renzo, A; Di Gennaro, F; Catalano, L; Califano, C; Pace, L; Rotoli, B; Salvatore, M

2001-02-01

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively 99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with 99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent 99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of 99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of 99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of 99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.

16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

PubMed

Lee, Byung Chul; Kim, Dong Hyun; Lee, Iljung; Choe, Yearn Seong; Chi, Dae Yoon; Lee, Kyung-Han; Choi, Yong; Kim, Byung-Tae

2008-06-26

We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate ( 2) and Na99mTcO 4 in the presence of Cr(CO)6 and CrCl3, followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41%ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that 99mTc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to 99mTc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.

Toward organometallic (99m)Tc imaging agents: synthesis of water-stable (99)Tc-NHC complexes.

PubMed

Benz, Michael; Spingler, Bernhard; Alberto, Roger; Braband, Henrik

2013-11-20

(99)Tc(V)O2-NHC complexes containing monodentate and bidentate N-heterocyclic carbenes (NHCs) have been prepared by the reactions of [TcO(glyc)2](-) (glyc = ethyleneglycolato) with 1,3-dimethylimidazoline-2-ylidene (L1), 1,1'-methylene-3,3'-dimethyl-4,4'-diimidazoline-2,2'-diylidene (L2), and 1,1'-methylene-3,3'-diethyl-4,4'-diimidazoline-2,2'-diylidene (L3) in THF. The resulting complexes were fully characterized and their stabilities investigated. While complexes with monodentate NHCs only are hydrolytically unstable, complexes containing bidentate NHCs are water-stable over a broad pH range. The high water stability allows interconversion of the {(99)Tc(V)O2}(+) core into {(99)Tc(V)OCl}(2+) with HCl as the H(+) and Cl(-) source. An alternative procedure to obtain (99)Tc(V)O2-NHC complexes is the in situ deprotonation of imidazolium salts, enabling the preparation of (99)Tc(V)O2-NHC compounds without free NHCs, thus increasing the scope of NHC ligands drastically. The remarkable stability and pH-controllable reactivity of the new complexes underlines the potential of NHCs as stabilizing ligands for (99)Tc complexes and paves the way for the first (99m)Tc-NHC complexes in the future.

Comparison of technetium-99m sulfur colloid and technetium-99m albumin colloid labeled solid meals for gastric emptying studies.

PubMed

Taillefer, R; Douesnard, J M; Beauchamp, G; Guimond, J

1987-08-01

A Tc-99m albumin colloid (Tc-AC) kit has been introduced as an alternative to Tc-99m sulfur colloid (Tc-SC) for liver-spleen imaging. Since there is no need for boiling, the use of Tc-AC reduces preparation time and manipulation. Tc-SC is one of the most commonly used radiopharmaceuticals for the labeling of solid-phase markers in gastric emptying studies. In vitro studies were performed to evaluate the labeling efficiency and stability in hydrochloric acid and in human gastric juice of intracellularly labeled chicken liver and scrambled eggs labeled with Tc-SC and Tc-AC. Gastric emptying studies also were performed on 20 healthy volunteers with both Tc-SC and Tc-AC labeled scrambled egg sandwiches. There was no significant difference between Tc-SC and Tc-AC in the labeling efficiency of chicken liver (98% +/- 1% for Tc-SC, 96% +/- 2% for Tc-AC) and scrambled eggs (92% +/- 2% for Tc-SC, 91% +/- 3% for Tc-AC). However, both Tc-SC and Tc-AC labeled scrambled eggs showed a lower stability than chicken liver, particularly in human gastric juice. Gastric emptying curves from both meals in 20 normal subjects were also similar, with a mean half-emptying time of 85 +/- 13 minutes and 87 +/- 16 minutes for the meals containing Tc-SC and Tc-AC respectively. Tc-AC is a reliable alternative to Tc-SC as a radiotracer for solid-phase gastric emptying studies.

Radiolabeled technetium chelates for use in renal function determinations

DOEpatents

Fritzberg, Alan; Kasina, Sudhaker; Johnson, Dennis L.

1994-01-01

The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is --H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

Radiolabeled technetium chelates for use in renal function determinations

DOEpatents

Fritzberg, Alan; Kasina, Sudhakar; Johnson, Dennis L.

1990-01-01

The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is--H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

99mTc-EDDA/HYNIC-octreotate in detection of atypical bronchial carcinoid.

PubMed

Hubalewska-Dydejczyk, A; Fröss-Baron, K; Gołkowski, F; Sowa-Staszczak, A; Mikołajczak, R; Huszno, B

2007-01-01

Pulmonary carcinoids cause serious difficulties in imaging diagnostics in all stages of the disease. SRS holds great promise for detecting occult primary tu and metastatic lesions. (99m)Tc-EDDA/HYNIC-octreotate, a new scintigraphic agent, should significantly improve sensitivity of the diagnostics of carcinoids due to better affinity to SSR2 than (111)In-Octreoscan and the higher count rate obtained from (99m)Tc over (111)In. We present a case of a 40-year-old women operated on because of lung carcinoid tumour in 2002. The symptoms did not resolve after the operation and 5-OHIAA was still elevated. The thorax spiral CT revealed the focal lesion beneath carina. (111)In-Octreoscan and (99m)Tc-EDDA/HYNIC-octreotate SRS revealed two focal lesions in the mediastinum. (99m)Tc-EDDA/HYNIC-octreotate detected two additional lesions in the lower part of the right lung. Target/non-target count ratios of the lesions were as follows: (99m)Tc-EDDA/HYNIC-octreotate scans - 2,9, (111)In-Octreoscan- 2,1. PET-FDG examination revealed no pathology. Owing to severe bone pains and carcinoid symptoms the patient was referred for the 90Y-DOTA-octreotate treatment. SRS with a new 99mTc marked somatostatin analogue - octreotate allows for a more sensitive detection of metastatic leasions in carcinoid tumours. The usefulness of 18F-FDG PET, widely used as a powerful imaging technique in clinical oncology, is limited in detection of carcinoid tumours due to the low proliferative activity.

Imaging human melanoma using a novel Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptide.

PubMed

Liu, Liqin; Xu, Jingli; Yang, Jianquan; Feng, Changjian; Miao, Yubin

2016-10-01

In this study, the human melanoma targeting property of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} was determined in M21 human melanoma-xenografts to demonstrate its potential for human melanoma imaging. The IC50 value of HYNIC-AocNle-CycMSHhex was 0.48±0.01nM in M21 human melanoma cells (1281receptors/cell). The M21 human melanoma uptake of (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex was 4.03±1.25, 3.26±1.23 and 3.36±1.48%ID/g at 0.5, 2 and 4h post-injection, respectively. Approximately 92% of injected dose cleared out the body via urinary system at 2h post-injection. (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex showed high tumor/blood, tumor/muscle and tumor/skin uptake ratios after 2h post-injection. The M21 human melanoma-xenografted tumor lesions were clearly visualized by SPECT/CT using (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex as an imaging probe at 2h post-injection. Overall, (99m)Tc(EDDA)-HYNIC-AocNle-CycMSHhex exhibited favorable human melanoma imaging property, highlighting its potential as an imaging probe for human metastatic melanoma detection. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel approach to infection imaging using a synthetic Tc-99m-labeled leukotactic peptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Som, P.; Oster, Z.H.; Sharma, S.

1996-05-01

RMT1, a synthetic peptide binding to PMN and macrophage receptors was labeled with Tc-99m and investigated as a potential imaging agent for abscess and inflammation. Experimental abscesses were induced in rabbits and dogs by turpentine and E.coli injection. After injection of Tc-99m-RMT1 two and twelve day old abscesses were visualized within 20 min. In initial studies, a dose of 30 {mu}g of peptide/3 mCi was used. This amount was subsequently reduced to 1.5 {mu}g peptide with same amount of Tc-99m yielding similar imaging results. Technetium-99m-IgG and Tc-99m-MAG-3 were used as positive and negative controls, respectively. After injection of IgG abscessesmore » were visualized but activity in blood was always higher than in abscess. When using Tc-99m RMT1 rapid abscess visualization and faster blood clearance was observed. The accumulation of RMT1 was monophasic, i.e., following the initial visualization, activity continued to build up continuously for 1{1/2} hr. Tc-99m-MAG3 accumulated initially in abscess, but activity washed out. In dogs, RMT1 blood clearance showed three components: a fast component with t{1/2}=1.9 min, 73%, intermediate t{1/2}=22 min, 24.5% and slow component, t{1/2}=115, 9.5% with 3 hours cumulative urine excretion of 40-51%. RMT1 appears to be more advantageous than currently available methods because of rapidity of imaging, simpler preparation before injection and will probably be less expensive and time consuming compared to labeled WBC. These results indicate that clinical experiments are warranted.« less

Two peptide receptor ligands (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide and (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin for scintigraphy of medullary thyroid carcinoma.

PubMed

Kosowicz, Jerzy; Mikołajczak, Renata; Czepczyński, Rafał; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy

2007-10-01

Somatostatin and gastrin receptors are overexpressed in medullary thyroid carcinoma (MTC) cells; hence, both of them are potential targets for peptide receptor scintigraphy and radiotherapy. Therefore, the aim of our study was to assess the clinical value of two technetium-99m-labeled peptides, a new gastrin analog, the EDDA/HYNIC-(D)Glu-octagastrin and a somatostatin analog, EDDA/HYNIC-Tyr(3)-octreotide (EDDA/HYNIC-TOC) for scintigraphy in patients with MTC to detect recurrences and metastases and select patients for peptide receptor radiotherapy. Thirty (30) patients, 20 females and 10 males, 22-83 years of age (mean, 52.7) with the diagnosis of MTC in different stages of the disease (preoperative, postsurgery, remission, recurrence, or metastatic disease) were included in this study. Before surgery, in all patients serum calcitonin concentrations were elevated. The diagnosis of MTC was confirmed in all cases by histopathology of the removed tumor and immunohistochemical staining giving positive reactions for calcitonin and chromogranin A. Imaging studies using (99m)Tc-EDDA/HYNIC-TOC and a new minigastrin analog, (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, were performed in each patient and the results compared with each other and with other imaging methods. Scans of the whole body, head, neck, and chest were performed 2 and 4 hours after injections of the tracer, 500-600 MBq in each case, using a double-head Varicam (Elscint, Israel) gamma camera. (99m)Tc-EDDA/HYNIC-TOC detected somatostatin receptor-positive lesions in 20 patients with MTC, whereas (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin displayed gastrin receptors in 11 patients. In 9 cases, the scans were positive in both methods, although in 2 cases different pathologic foci were visualized. In 12 cases, only (99m)Tc-EDDA/HYNIC-TOC scintigraphy was positive, whereas in 3 other cases only (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin revealed pathologic lesions. Scintigraphy using (99m)Tc-HYNIC-TOC permits the visualization of somatostatin receptor-positive MTC in the majority of cases. The new gastrin analog, (99m)Tc-HYNIC-(D)Glu-octagastrin, is well tolerated, shows no renal retention, and in some cases of MTC, provides additional information on the expression of gastrin receptors. However, inferior quality of octagastrin scans indicates the need for further improvement of this radiopeptide.

[The scintigraphic 99mTc-MAA imaging quantification of the right-to-left shunt in a patients with multiple pulmonary arteriovenous malformation and familial teleangiectasis].

PubMed

Dolezal, J

2008-02-01

To present a case report about 57-years-old woman with hypoxemia, multiple pulmonary arteriovenous (AV) malformations and lips teleangiectasis where the right-to-left shunt quantification was assessed by means of whole body scintigraphy with 9mTc-labelled human macro-aggregated albumin (MAA). A 57-years-old woman underwent X-ray and bolus enhanced lung CT for dyspnoea, hypoxemia and cyanosis. A multiple intrapulmonary arteriovenous malformations were detected. The whole-body 99mTc-MAA scintigraphy for the right-to-left shunt quantification was performed. The whole-body scintigraphy in anterior and posterior view was started after intravenous application of 185 MBq 99mTc-MAA. The double-head gamma camera Infinia (General Electric Medical Systems--GE MS) with infrared body countouring and the large field of view was used. The Gamma camera was fitted with low-energy, high resolution, parallel-hole collimator. Images were evaluated by processing system Xeleris (GE MS). The whole-body 99mTc-MAA scintigraphy revealed significant R-L shunt and uptake of radiotracer in extrapulmonary organs (brain, kidney, spleen). The right-to-left shunt ratio was 36%. The woman underwent successful percutaneous transcatheter microembolization treatment. After treatment the woman underwent the next 99mTc-MAA whole-body scintigraphy and the R-L shunt ratio decreased to 17%. The 99mTc-MAA whole-body scintigraphy assessed the right-to-left shunt ratio and improved the management of patients with multiple intrapulmonary A-V malformations. The next 99mTc-MAA scintigraphy after the percutaneous transcatheter microembolization of multiple intrapulmonary A-V malformations confirmed success of treatment.

Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests.

PubMed

Kartamihardja, A H S; Kurniawati, Y; Gunawan, R

2018-01-01

Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using 99m Tc. 99m Tc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of 99m Tc-ethambutol scintigraphy in detecting and localizing of TB. Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370-555 MBq 99m Tc-ethambutol. 99m Tc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy. One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between 99m Tc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of 99m Tc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study. 99m Tc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral ^99mTc-colloid Sentinel Node Lymphoscintigraphy.

PubMed

Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

2017-08-24

Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oxidation of methionine - is it limiting the diagnostic properties of 99mTc-labeled Exendin-4, a Glucagon-Like Peptide-1 receptor agonist?

PubMed

Janota, Barbara; Karczmarczyk, Urszula; Laszuk, Ewa; Garnuszek, Piotr; Mikołajczak, Renata

2016-01-01

Preliminary clinical evaluation of 99mTc-EDDA/HYNIC-Met14-Exendin-4 showed that the complex offers new diagnostic possibilities for insulinoma and MTC. Exendin-4 contains methionine at position 14 in the amino acid chain, which may be oxidized to methionine sulfoxide and, from the pharmaceutical point of view, the oxidized moiety becomes an undesired impurity in the final radioactive preparation. Therefore, the aim of this study was to investigate the influence of commonly used methods to eliminate the effect of methionine oxidation in peptides, i.e. the replacement of methionine by norleucine (Nle) and the addition of L-methionine, on the in vitro stability and the biodistribution. 99mTc-EDDA/HYNIC-Met14-Exendin-4, 99mTc-EDDA/HYNIC-Nle14-Exendin-4, 99mTc-EDDA/HYNIC-Met14-Ex-endin-4 with the addition of L-methionine and an oxidized form of Exendin-4, i.e. 99mTc-EDDA/HYNIC-Met14(ox)-Exendin-4 were compared in vivo with 68Ga-NODAGA-Nle14-Exendin-4 in normal Wistar rats. The stability and lipophilicity were determined in vitro. Biodistribution studies confirmed the specific uptake of all tested complexes in the GLP-1 positive organs: lungs, pancreas and stomach. The uptake of 99mTc-EDDA/HYNIC-Met14-Exendin-4 with the addition of L-methionine and for 68Ga-NODAGA-Nle14-Exendin-4 at 1h p.i. was around 2-fold higher than that of 99mTc-EDDA/HYNIC-Met14-Exendin-4 and 99mTc-EDDA/HYNIC-Nle14-Exendin-4. Although the substitution of methionine by norleucine in the HYNIC-Exendin-4 did not result in improved bio-distribution, the use of L-methionine, as the excipient that inhibits the oxidation of methionine in the peptide chain resulted in higher lung/blood and stomach/blood uptake ratios. Our results confirmed that methionine at position 14 of amino acid chain of Exendin-4 plays an important role in the interaction with GLP-1 receptor positive tissue.

Measurement of translymphatic fluid absorption using technetium-99m human serum albumin diethylenetriamine pentaacetic acid in continuous ambulatory peritoneal dialysis patients.

PubMed

Terawaki, Hiroyuki; Nakayama, Masaaki; Seto, Kazuhiko; Yoshimura, Kazunobu; Hasegawa, Toshio

2004-08-01

We have established a new method of measuring translymphatic fluid absorption (TLA) using technetium-99m ((99m)Tc) human serum albumin diethylenetriamine pentaacetic acid ((99m)Tc-HSAD) that can be used commonly in clinical practice. This new method was applied in 13 continuous ambulatory peritoneal dialysis patients (11 males and two females) who had various peritoneal permeability and capacities for peritoneal transport of water. (99m)Tc-HSAD 740MBq was injected in 2 L of peritoneal dialysis fluid with 2.5% glucose, mixed well, and administered intraperitoneally. The fluid was drained extraperitoneally after 4 h and TLA was determined by the in vivo loss of (99m)Tc-HSAD. TLA was 1.41 +/- 1.11 mL/min (mean +/- SD; range, 0.27-3.69 mL/min). The estimated reduction rate by TLA in trans-peritoneally removed fluid ranged from 14.2 to 84.4%, indicating that TLA could have an extremely significant negative effect in some cases on total drainage volume. The present study, using new tracer (99m)Tc-HSAD, could confirm a large individual difference in TLA, indicating TLA as an important contributing factor for fluid-removal failure in continuous ambulatory peritoneal dialysis patients.

Characterization of TCP-1 probes for molecular imaging of colon cancer.

PubMed

Liu, Zhonglin; Gray, Brian D; Barber, Christy; Bernas, Michael; Cai, Minying; Furenlid, Lars R; Rouse, Andrew; Patel, Charmi; Banerjee, Bhaskar; Liang, Rongguang; Gmitro, Arthur F; Witte, Marlys H; Pak, Koon Y; Woolfenden, James M

2016-10-10

Molecular probes capable of detecting colorectal cancer (CRC) are needed for early CRC diagnosis. The objective of this study was to characterize c[CTPSPFSHC]OH (TCP-1), a small peptide derived from phage display selection, for targeting human CRC xenografts using technetium-99m ((99m)Tc)-labeled TCP-1 and fluorescent cyanine-7 (Cy7)-labeled form of the peptide (Cy7-TCP-1). (99m)Tc-TCP-1 was generated by modifying TCP-1 with succinimidyl-6-hydrazino-nicotinamide (S-HYNIC) followed by radiolabeling. In vitro saturation binding experiments were performed for (99m)Tc-TCP-1 in human HCT116 colon cancer cells. SCID mice with human HCT116 cancer xenografts were imaged with (99m)Tc-TCP-1 or control peptide using a small-animal SPECT imager: Group I (n=5) received no blockade; Group II (n=5) received a blocking dose of non-radiolabeled TCP-1. Group III (n=5) were imaged with (99m)Tc-labeled control peptide (inactive peptide). SCID mice with human PC3 prostate cancer xenografts (Group IV, n=5) were also imaged with (99m)Tc-TCP-1. Eight additional SCID mice bearing HCT116 xenografts in dorsal skinfold window chambers (DSWC) were imaged by direct positron imaging of (18)F-fluorodeoxyglucose ((18)F-FDG) and fluorescence microscopy of Cy7-TCP-1. In vitro(99m)Tc-HYNIC-TCP-1 binding assays on HCT 116 cells indicated a mean Kd of 3.04±0.52nM. In cancer xenografts, (99m)Tc-TCP-1 radioactivity (%ID/g) was 1.01±0.15 in the absence of blockade and was reduced to 0.26±0.04 (P<0.01) with blockade. No radioactive uptake was observed in the PC3 tumors with (99m)Tc-TCP-1 or HCT116 tumors with inactive peptide. Cy7-TCP-1 activity localized not only in metabolically active tumors, as defined by (18)F-FDG imaging, but also in peritumoral microvasculature. In conclusion, TCP-1 probes may have a distinct targeting mechanism with high selectivity for CRC and tumor-associated vasculature. Molecular imaging with TCP-1 probes appears promising to detect malignant colorectal lesions. Copyright © 2016 Elsevier B.V. All rights reserved.

Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: Experimental and clinical investigations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suga, Kazuyoshi; Uchisako, Hiromichi; Nishigauchi, Kazuya

1994-09-01

The authors evaluated the ability of {sup 99m}Tc-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) to serve as a sensitive marker of lung injury. Two experiment rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, they clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of {sup 99m}Tc-HMPAO in the lungs. Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of {supmore » 99m}Tc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of {sup 99m}Tc-HMPAO activity in the patients who received chemotherapy (0.649{+-}0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387{+-}0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. These findings suggest that {sup 99m}Tc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury. 53 refs., 5 figs., 3 tabs.« less

Radionuclide imaging of myocardial infarction using Tc-99m TBI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holman, B.L.; Campbell, S.; Kirshenbaum, J.M.

The cationic complex Tc-99m t-butylisonitrile (TBI) concentrates in the myocardial tissue of several animal species. Its myocardial distribution is proportional to blood flow both in zones of ischemia and in normal myocardium at rest. Planar, tomographic, and gated myocardial images have been obtained using Tc-99m TBI in the human. The authors investigated the potential application of Tc-99m TBI imaging to detect and localize myocardial infarction. Four subjects without clinical evidence of cardiovascular disease and five patients with ECG evidence of previous myocardial infarction were studied. Tc-99m TBI (10mCi) was injected intravenously with the patient in a resting state with planarmore » imaging in the anterior, 30 and 70 degree LAO projections beginning one hr after injection. The distribution of the tracer was homogeneous throughout the left ventricular wall in the normal subjects. Regional perfusion defects were present in 4/5 of the patients with myocardial infarction. Location of the defects corresponded to the location of the infarct using ECG criteria (2 inferoposterior and 2 anterior). The patient in whom the Tc-99m TBI image appeared normal had sustained a subendocardial myocardial infarct which could not be localized by ECG; the other 4 pts had transmural infarcts. Anterior and 30 degree LAO images were of excellent quality in all cases; there was overlap of the liver on the inferior wall of the left ventricle on the 70 degree LAO views. The authors conclude that accurate perfusion imaging may be possible using Tc-99m TBI in patients with transmural myocardial infarction.« less

Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P.

PubMed

Smilkov, Katarina; Janevik, Emilija; Guerrini, Remo; Pasquali, Micol; Boschi, Alessandra; Uccelli, Licia; Di Domenico, Giovanni; Duatti, Adriano

2014-09-01

New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of americium-241 and technetium-99m as transmission sources for attenuation correction of thallium-201 SPECT imaging of the heart.

PubMed

Ficaro, E P; Fessler, J A; Rogers, W L; Schwaiger, M

1994-04-01

This study compares the ability of 241Am and 99mTc to estimate 201Tl attenuation maps while minimizing the loss in the precision of the emission data. A triple-head SPECT system with either an 241Am or 99mTc line source opposite a fan-beam collimator was used to estimate attenuation maps of the thorax of an anthropomorphic phantom. Linear attenuation values at 75 keV for 201Tl were obtained by linear extrapolation of the measured values from 241Am and 99mTc. Lung and soft-tissue estimates from both isotopes showed excellent agreement to within 3% of the measured values for 201Tl. Linear extrapolation did not yield satisfactory estimates for bone from either 241Am (+11.7%) or 99mTc (-15.3%). Patient data were used to estimate the dependence of crosstalk on patient size. Contamination from 201Tl in the transmission window was 5-6 times greater for 241Am compared to 99mTc, while the contamination in the 201Tl data in the transmission-emission detector head (head 1) was 4-5 times greater for 99mTc compared to 241Am. No contamination was detected in the 201Tl emission data of heads 2 and 3 from 241Am, whereas the 99mTc produced a small crosstalk component giving a signal-to-crosstalk ratio near 20:1. Measurements with a fillable chest phantom estimated the mean error introduced into the data from the removal of the crosstalk. Based on the measured data, 241Am is a suitable transmission source for simultaneous transmission-emission tomography for 201Tl cardiac studies.

Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

PubMed

Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Myoung Hyoun; Kim, Dae-Weung; Park, Cho Rong; Park, Ji Yong; Lee, Yun-Sang; Youn, Hyewon; Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key

2016-06-01

The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE. The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co-administered. Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors.

Large telangiectatic focal nodular hyperplasia presenting with normal radionuclide studies: Case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterfy, C.G.; Rosenthall, L.

1990-12-01

A 9 cm-lesion of telangiectatic focal nodular hyperplasia was incidentally identified in a 31-yr-old female. Despite a typical appearance by X-ray computed tomography and ultrasonography, scintigraphy with technetium-99m-({sup 99m}Tc) colloid, {sup 99m}Tc-diethyliminodiacetic acid, and {sup 99m}Tc-labeled red cells failed to demonstrate any abnormalities. These findings are felt to reflect the relative lack of architectural disruption that histologically characterizes this particular lesion. The present report described the imaging characteristics of the telangiectatic form of focal nodular hyperplasia.

SPECT measurements with /sup 99m/Tc-HM-PAO in focal epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryding, E.; Rosen, I.; Elmqvist, D.

1988-12-01

The ability of SPECT measurements with (/sup 99m/Tc)-HM-PAO (Ceretec) to find the location of the epileptic focus was studied in patients under consideration for neurosurgical treatment for therapy-resistant focal epilepsy. The location of low (/sup 99m/Tc)-HM-PAO uptake regions found at interictal measurements, and of high (/sup 99m/Tc)-HM-PAO uptake regions found at ictal measurements, was compared to the findings of extensive ictal and interictal EEG examinations, and to the results of CT and MRT. While EEG revealed focal epileptic activity in all of the 14 patients, SPECT showed regional abnormalities in 13 (93%). CT and MRT showed abnormal findings in 30%.

Tc-99m Hydroxymethylene Diphosphonate (HMDP) Renal Uptake as a Surrogate Marker of Postoperative Impairment of the Glomerular Filtration Rate in Renal Tumor Patients Following Nephron-Sparing Surgery.

PubMed

Choi, Hongyoon; Lee, Won Woo; So, Young; Ha, Seunggyun; Byun, Seok-Soo; Kim, Sang Eun

2014-12-01

We investigated Tc-99m hydroxymethylene diphosphonate (HMDP) scintigraphy findings in renal tumor patients from the perspective of postoperative renal dysfunction following nephron-sparing surgery (NSS). Forty-three renal tumor patients (M:F = 28:15, age 53.9 ± 12.5 years) who had undergone Tc-99m HMDP scintigraphy after NSS were enrolled. The patients were divided into HMDP(+) or HMDP(-) groups by visual assessment, and the asymmetric index (ASI) was calculated using a region-of-interest analysis. In 16 patients, the total and split glomerular filtration rate (GFR) was assessed using Tc-99m diethylenetriaminepentaacetic acid (DTPA) scintigraphy at baseline and at 3 and 6 months post-NSS. High Tc-99m HMDP uptake was observed in the operated kidneys, but this did not persist later than 7 days post-NSS. Split GFR of the operated kidneys at baseline (58.5 ± 9.3 ml/min) was significantly reduced at 6 months post-NSS (40.1 ± 5.9 ml/min, p < 0.001) in only those who showed intense uptake of Tc-99m HMDP. Declines in both total GFR (p = 0.010 and p = 0.002 for 3 and 6 months, respectively) and split GFR of the operated kidneys (p < 0.001 and p < 0.001 for 3 and 6 months, respectively) were clearly evidenced at 3 and 6 months post-NSS only in patients with high Tc-99m HMDP in the operated kidneys. The ASI was negatively correlated with %change in the split GFR of these operated kidneys at 6 months post-NSS (rho =-0.578, p = 0.0304). Tc-99m HMDP uptake within 1 week following NSS is a surrogate marker of GFR impairment over 6 months post-NSS.

A modified TEW approach to scatter correction for In-111 and Tc-99m dual-isotope small-animal SPECT.

PubMed

Prior, Paul; Timmins, Rachel; Petryk, Julia; Strydhorst, Jared; Duan, Yin; Wei, Lihui; Glenn Wells, R

2016-10-01

In dual-isotope (Tc-99m/In-111) small-animal single-photon emission computed tomography (SPECT), quantitative accuracy of Tc-99m activity measurements is degraded due to the detection of Compton-scattered photons in the Tc-99m photopeak window, which originate from the In-111 emissions (cross talk) and from the Tc-99m emission (self-scatter). The standard triple-energy window (TEW) estimates the total scatter (self-scatter and cross talk) using one scatter window on either side of the Tc-99m photopeak window, but the estimate is biased due to the presence of unscattered photons in the scatter windows. The authors present a modified TEW method to correct for total scatter that compensates for this bias and evaluate the method in phantoms and in vivo. The number of unscattered Tc-99m and In-111 photons present in each scatter-window projection is estimated based on the number of photons detected in the photopeak of each isotope, using the isotope-dependent energy resolution of the detector. The camera-head-specific energy resolutions for the 140 keV Tc-99m and 171 keV In-111 emissions were determined experimentally by separately sampling the energy spectra of each isotope. Each sampled spectrum was fit with a Linear + Gaussian function. The fitted Gaussian functions were integrated across each energy window to determine the proportion of unscattered photons from each emission detected in the scatter windows. The method was first tested and compared to the standard TEW in phantoms containing Tc-99m:In-111 activity ratios between 0.15 and 6.90. True activities were determined using a dose calibrator, and SPECT activities were estimated from CT-attenuation-corrected images with and without scatter-correction. The method was then tested in vivo in six rats using In-111-liposome and Tc-99m-tetrofosmin to generate cross talk in the area of the myocardium. The myocardium was manually segmented using the SPECT and CT images, and partial-volume correction was performed using a template-based approach. The rat heart was counted in a well-counter to determine the true activity. In the phantoms without correction for Compton-scatter, Tc-99m activity quantification errors as high as 85% were observed. The standard TEW method quantified Tc-99m activity with an average accuracy of -9.0% ± 0.7%, while the modified TEW was accurate within 5% of truth in phantoms with Tc-99m:In-111 activity ratios ≥0.52. Without scatter-correction, In-111 activity was quantified with an average accuracy of 4.1%, and there was no dependence of accuracy on the activity ratio. In rat myocardia, uncorrected images were overestimated by an average of 23% ± 5%, and the standard TEW had an accuracy of -13.8% ± 1.6%, while the modified TEW yielded an accuracy of -4.0% ± 1.6%. Cross talk and self-scatter were shown to produce quantification errors in phantoms as well as in vivo. The standard TEW provided inaccurate results due to the inclusion of unscattered photons in the scatter windows. The modified TEW improved the scatter estimate and reduced the quantification errors in phantoms and in vivo.

Semi-Quantitative Analysis of Post-Transarterial Radioembolization (90)Y Microsphere Positron Emission Tomography Combined with Computed Tomography (PET/CT) Images in Advanced Liver Malignancy: Comparison With (99m)Tc Macroaggregated Albumin (MAA) Single Photon Emission Computed Tomography (SPECT).

PubMed

Rhee, Seunghong; Kim, Sungeun; Cho, Jaehyuk; Park, Jukyung; Eo, Jae Seon; Park, Soyeon; Lee, Eunsub; Kim, Yun Hwan; Choe, Jae-Gol

2016-03-01

The purpose of this study is to evaluate the correlation between pretreatment planning technetium-99m ((99m)Tc) macroaggregated albumin (MAA) SPECT images and posttreatment transarterial radioembolization (TARE) yttirum-90 ((90)Y) PET/CT images by comparing the ratios of tumor-to-normal liver counts. Fifty-two patients with advanced hepatic malignancy who underwent (90)Y microsphere radioembolization from January 2010 to December 2012 were retrospectively reviewed. Patients had undergone (99m)Tc MAA intraarterial injection SPECT for a pretreatment evaluation of microsphere distribution and therapy planning. After the administration of (90)Y microspheres, the patients underwent posttreatment (90)Y PET/CT within 24 h. For semiquantitative analysis, the tumor-to-normal uptake ratios in (90)Y PET/CT (TNR-yp) and (99m)Tc MAA SPECT (TNR-ms) as well as the tumor volumes measured in angiographic CT were obtained and analyzed. The relationship of TNR-yp and TNR-ms was evaluated by Spearman's rank correlation and Wilcoxon's matched pairs test. In a total of 79 lesions of 52 patients, the distribution of microspheres was well demonstrated in both the SPECT and PET/CT images. A good correlation was observed of between TNR-ms and TNR-yp (rho value = 0.648, p < 0.001). The TNR-yp (median 2.78, interquartile range 2.43) tend to show significantly higher values than TNR-ms (median 2.49, interquartile range of 1.55) (p = 0.012). The TNR-yp showed weak correlation with tumor volume (rho = 0.230, p = 0.041). The (99m)Tc MAA SPECT showed a good correlation with (90)Y PET/CT in TNR values, suggesting that (99m)Tc MAA can be used as an adequate pretreatment evaluation method. However, the (99m)Tc MAA SPECT image consistently shows lower TNR values compared to (90)Y PET/CT, which means the possibility of underestimation of tumorous uptake in the partition dosimetry model using (99m)Tc MAA SPECT. Considering that (99m)Tc MAA is the only clinically available surrogate marker for distribution of microsphere, we recommend measurement of tumorous uptake using (90)Y PET/CT should be included routinely in the posttherapeutic evaluation.

99 mTc-MIBI washout as a complementary factor in the evaluation of idiopathic dilated cardiomyopathy (IDCM) using myocardial perfusion imaging.

PubMed

Shiroodi, Mohammad Kazem; Shafiei, Babak; Baharfard, Nastaran; Gheidari, Mohammad Esmail; Nazari, Babak; Pirayesh, Elaheh; Kiasat, Ali; Hoseinzadeh, Samaneh; Hashemi, Abolghassem; Akbarzadeh, Mohammad Ali; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid

2012-01-01

Rapid technetium-99 m methoxyisobutylisonitrile (99 mTc-MIBI) washout has been shown to occur in impaired myocardia. This study is based on the hypothesis that scintigraphy can be applied to calculate the myocardial 99 mTc-MIBI washout rate (WR) to diagnose and evaluate heart failure severity and other left ventricular functional parameters specifically in idiopathic dilated cardiomyopathy (IDCM) patients. Patients with IDCMP (n = 17; 52.65 ± 11.47 years) and normal subjects (n = 6; 49.67 ± 10.15 years) were intravenously administered 99 mTc-hexakis-2-methoxyisobutylisonitrile (99 mTc-MIBI). Next, early and delayed planar data were acquired (at 3.5-h intervals), and electrocardiogram (ECG)-gated myocardial perfusion single photon emission computed tomography (SPECT) was performed. The 99 mTc-MIBI WR was calculated using early and delayed planar images. Left ventricular functional parameters were also analyzed using quantitative gated SPECT (QGS) data. In target group, myocardial WRs (29.13 ± 6.68%) were significantly higher than those of control subjects (14.17 ± 3.31%; P < 0.001). The 99 mTc-MIBI WR increased with the increasing severity of the NYHA functional class (23.16 ± 1.72% for class I, 30.25 ± 0.95% for class II, 32.60 ± 6.73% for class III, and 37.50 ± 7.77% for class IV; P = 0.02). The WR was positively correlated with the end-diastolic volume (EDV) index (r (2) = 0.216; β = 0.464; P = 0.02 [ml/m(2)], the end-systolic volume (ESV) index (r (2) = 0.234; β = 0.484; P = 0.01 [ml/m(2)]), the summed motion score (SMS) (r (2) = 0.544; β = 0.738; P = 0.00), and the summed thickening score (STS) (r (2) = 0.656; β = 0.810; P = 0.00); it was negatively correlated with the left ventricular ejection fraction (LVEF) (r (2) = 0.679; β = -0.824; P = 0.00). It can be concluded that 99 mTc-MIBI scintigraphy might be a valuable molecular imaging tool for the diagnosis and evaluation of myocardial damage or dysfunction severity.

Influence of time delay on the estimated lung shunt fraction on 99mTc-labeled MAA scintigraphy for 90Y microsphere treatment planning.

PubMed

De Gersem, Ruth; Maleux, Geert; Vanbilloen, Hubert; Baete, Kristof; Verslype, Chris; Haustermans, Karin; Verbruggen, Alfons; Van Cutsem, Eric; Deroose, Christophe Michel

2013-12-01

90Y-microspheres therapy is used to treat selected patients with primary or metastatic liver tumors in a safe and effective way. As a preparation for 90Y-microspheres treatment, a 99mTc-macroaggregated albumin (99mTc-MAA) simulation procedure is essential to evaluate particle shunting to the lung or gastrointestinal tract. We investigated the effect of interval between injection of 99mTc-MAA and time of scanning on the lung shunt fraction (LSF). In 4 patients with secondary hepatic malignancies who underwent repeated whole-body scintigraphy up to 5 hours after injection of 99mTc-MAA, a marked change in LSF was observed. It appears that tracer degradation leads to an important overestimation of LSF at later time points. An overestimation of LSF can lead to dose reduction or canceling of the planned 90Y-microspheres treatment. It is concluded that the interval between injection and scanning should be kept as short as possible.

(99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study.

PubMed

Essa, B M; Sakr, T M; Khedr, Mohammed A; El-Essawy, F A; El-Mohty, A A

2015-08-30

Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend (99m)Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of 99mTc-ECD SPECT in the Management of Children with Craniosynostosis

PubMed Central

Barik, Mayadhar; Bajpai, Minu; Das, Rashmi Ranajn; Malhotra, Arun; Panda, Shasanka Shekhar; Sahoo, Manas Kumar; Dwivedi, Sadanand

2014-01-01

Purpose of the Report. There is a paucity of data on correlation of various imaging modalities with clinical findings in craniosynostosis. Moreover, no study has specifically reported the role of 99mTc-ECD SPECT in a large number of subjects with craniosynostosis. Materials and Methods. We prospectively analyzed a cohort of 85 patients with craniosynostosis from year 2007 to 2012. All patients underwent evaluation with 99mTc-ECD SPECT and the results were correlated with radiological and surgical findings. Results. 99mTc-ECD SPECT revealed regional perfusion abnormalities in the cerebral hemisphere corresponding to the fused sutures preoperatively that disappeared postoperatively in all the cases. Corresponding to this, the mean mental performance quotient (MPQ) increased significantly (P < 0.05) postoperatively only in those children with absent perfusion defect postoperatively. Conclusions. Our study suggests that early surgery and release of craniosynostosis in patients with preoperative perfusion defects (absent on 99mTc-ECD SPECT study) are beneficial, as theylead to improved MPQ after surgery. PMID:24987670

Tc-99m tilmanocept versus Tc-99m sulfur colloid in breast cancer sentinel lymph node identification: Results from a randomized, blinded clinical trial.

PubMed

Unkart, Jonathan T; Hosseini, Ava; Wallace, Anne M

2017-12-01

No prior trials have compared sentinel lymph node (SLN) identification outcomes between Tc-99m tilmanocept (TcTM) and Tc-99m sulfur colloid (TcSC) in breast cancer (BC). We report on the secondary outcomes from a randomized, double-blinded, single surgeon clinical trial comparing post-injection site pain between TcTM and TcSC. Patients were randomized to receive a preoperative single, peritumoral intradermal injection of TcTM or TcSC. The number of total, "hot", and blue nodes detected and removed were compared between groups. Fifty-two (27-TcSC and 25-TcTM) patients were enrolled and underwent definitive surgical treatment. At least one "hot" SLN was detected in all patients. Three (5.8%) patients had a disease positive-SLN. The total number of SLNs removed was 61 (mean 2.26 (standard deviation (SD) 0.90)) in the TcSC group and 54 (mean 2.16 (SD 0.90)) in the TcTM group, P = 0.69. The total number of "hot" nodes in the TcSC group was 1.96 (SD 0.76) compared to 2.04 (SD 0.73) in the TcTM group, P = 0.71. The number of identified SLNs did not differ significantly between TcTM and TcSC. Given that no significant technical advantages exist between the two agents, surgeons should choose a radiopharmaceutical based on cost and side effect profile. © 2017 Wiley Periodicals, Inc.

PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

PubMed

Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

2010-11-01

A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ might confer to this novel compound an important role for the development of new (99m)Tc and (188)Re-nitrido radiopharmaceuticals. Copyright © 2010 Elsevier Inc. All rights reserved.

Indigenous technology development and standardization of the process for obtaining ready to use sterile sodium pertechnetate-Tc-99m solution from Geltech generator

PubMed Central

Sarkar, Sishir Kumar; Kothalkar, Chetan; Naskar, Prabhakar; Joshi, Sangeeta; Saraswathy, Padmanabhan; Dey, Arun Chandra; Vispute, Gunvant Leeladhar; Murhekar, Vishwas Vinayak; Pilkhwal, Neelam

2013-01-01

Purpose of the Study: The indigenous design and technology development for processing large scale zirconium molybdate-Mo-99 (ZrMo-99) Geltech generator was successfully commissioned in Board of Radiation and Isotope Technology (BRIT), India, in 2006. The generator production facility comprises of four shielded plant facilities equipped with tongs and special process gadgets amenable for remote operations for radiochemical processing of ZrMo-99 gel. Results: Over 2800 Geltech generators have been processed and supplied to user hospitals during the period 2006-2013. Geltech generator supplied by BRIT was initially not sterile. Simple elution of Tc-99m is performed by a sterile evacuated vial with sterile and pyrogen free 0.9% NaCl solution to obtain sodium (Tc-99m) pertechnetate solution. A special type online 0.22 μm membrane filter has been identified and adapted in Geltech generator. Conclusions: The online filtration of Tc-99m from Geltech generator; thus, provided sterile Tc-99m sodium pertechnetate solution. Generators assembled with modified filter assembly were supplied to local hospital in Mumbai Radiation Medicine Centre (RMC) and S.G.S. Medical College and KEM Hospital) and excellent performances were reported by users. PMID:24163509

Differences between the macroscopic and tracer level chemistry of rhenium and technetium: contrasting cage isomerisation behaviour of Re(I) and Tc(I) carborane complexes.

PubMed

Armstrong, Andrea F; Valliant, John F

2010-09-21

Carboranes form stable complexes with the [M(CO)(3)](+) (M = (99m)Tc, Re) core and are viable ligands for the development of targeted radiopharmaceuticals. (99m)Tc-carborane complexes were found to exhibit substantially different 1,2-->1,7 cage isomerisation behaviour than their Re counterparts, challenging the validity of the routine use of rhenium as a surrogate for the development of technetium-99m based molecular imaging agents.

The Design and Emulation of a Multiple-Camera SPECT Breast Imager

DTIC Science & Technology

1998-06-01

geometry. Standard clinical injections of Tc-99m Sestamibi contain 20 mCi of activity The estimated percentage of the activity taken up by a single...was to work on five tasks. (1) Given a female patient in the clinic who had been injected with Tc-99m Sestamibi, what percentage of the injected...25 mCi of Tc-99m Sestamibi and undergone imaging on standard clinical instruments for other medical reasons. Upon completion of those studies, the

Influence of Storage Temperature on Radiochemical Purity of 99mTc-Radiopharmaceuticals.

PubMed

Uccelli, Licia; Boschi, Alessandra; Martini, Petra; Cittanti, Corrado; Bertelli, Stefania; Bortolotti, Doretta; Govoni, Elena; Lodi, Luca; Romani, Simona; Zaccaria, Samanta; Zappaterra, Elisa; Farina, Donatella; Rizzo, Carlotta; Giganti, Melchiore; Bartolomei, Mirco

2018-03-15

The influence of effective room temperature on the radiochemical purity of 99m Tc-radiopharmaceuticals was reported. This study was born from the observation that in the isolators used for the preparation of the 99m Tc-radiopharmaceuticals the temperatures can be higher than those reported in the commercial illustrative leaflets of the kits. This is due, in particular, to the small size of the work area, the presence of instruments for heating, the continuous activation of air filtration, in addition to the fact that the environment of the isolator used for the 99m Tc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned. A total of 244 99m Tc-radiopharmaceutical preparations (seven different types) have been tested and the radiochemical purity was checked at the end of preparation and until the expiry time. Moreover, we found that the mean temperature into the isolator was significantly higher than 25 °C, the temperature, in general, required for the preparation and storage of 99m Tc-radiopharmaceuticals. Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required in the field of quality assurance, the impact that different conditions than those required by the manufacturer on the radiopharmaceuticals quality have to be verified before human administration.

[Evaluation of left ventricular diastolic function using gated SPECT with 99mTc-MIBI].

PubMed

Toba, M; Kumita, S I; Mizumura, S; Cho, K; Kijima, T; Takahama, K; Kumazaki, T

1996-04-01

Development of 3 head SPECT system and 99mTc-labeled radiopharmaceuticals enable us to evaluate left ventricular systolic function on the basis of once gated SPECT routine. This study was focused on assessment of left ventricular diastolic function using 99mTc-MIBI gated SPECT data. Twenty nine patients with ischemic heart diseases underwent 99mTc-MIBI gated SPECT and 99mTc-HSAD ventriculographic assessment of left ventricular diastolic function within 1 month. Region of interests (ROI), simultaneously calculating counts per pixel within ROI, were placed over whole myocardium of 16 serial phasic images reconstructed from gated SPECT data, following selection of the central slice within short axial images. Then, 29 patients were classified into 3 patterns of phase count curve (normal, mixed, and delayed relaxation = diastolic dysfunction). Moreover, 1/3 Count Decreasing Fraction (1/3 CDF) was calculated on the same concept as 1/3 FF. The curve pattern showed significant differences between normal and abnormal group divided on the basis of established indices such as 1/3 FF and PFR, and 1/3 CDF has correlations with 1/3 FF (r = 0.61) and PFR (r = 0.58). We concluded that the new parameters drawn from 99mTc-MIBI gated SPECT data might be feasible for evaluation of diastolic function.

Hydroxyapatite Based 99Mo - 99Tc and 188W - 188Re Generator Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp Jr, Russ F; Monroy-Guzman, F.; Badillo, V. E.

2006-01-01

This paper describes studies evaluating the use of hydroxyapatite as the adsorbent material for both {sup 99}Mo-{sup 99m}Tc and {sup 188}W-{sup 188}Re generator systems. Hydroxyapatite is an insoluble solid with anion exchange properties. A study of the sorption behaviour of {sup 99}Mo, {sup 99m}Tc, {sup 188}W and {sup 188}Re on hydroxyapatite in NaCl medium was evaluated by batch experiments. The results demonstrated that while {sup 99}Mo, {sup 99m}Tc and {sup 188}Re are not adsorbed by the hydroxyapatite in NaCl solutions (Kd <5), {sup 188}W is strongly adsorbed (Kd >500). On the basis of these measurements, hydroxyapatite {sup 188}W-{sup 188}Re generatormore » systems were then constructed and eluted in NaCl solutions. The hydroxyapatite based {sup 188}W-{sup 188}Re generator performances are presented.« less

Synthesis of tripeptide derivatized cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes.

PubMed

Nadeem, Qaisar; Can, Daniel; Shen, Yunjun; Felber, Michael; Mahmood, Zaid; Alberto, Roger

2014-03-28

We describe the syntheses of half-sandwich complexes of the type [(η(5)-Cp(CONH-R))M(CO)3] with M = Re or (99m)Tc. The R group represents different tri-peptides (tpe) which display high binding affinities for oligopeptide transporters PEPT2. The (99m)Tc complexes were prepared directly from [(99m)Tc(OH2)3(CO)3](+) and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels-Alder reactions for the preparation of not only small molecules but also peptides carrying a [(η(5)-Cp)(99m)Tc(CO)3] tag. We synthesized the Diels-Alder product [(HCpCONH-tpe)2] from Thiele's acid [(η(5)-HCpCOOH)2] via double peptide coupling. The Re-complexes [(η(5)-CpCONH-tpe)Re(CO)3] were obtained by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as received from SPPS. The authenticity of the (99m)Tc-complexes is confirmed by chromatographic comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.

pH-Sensitive, Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors: a Feasibility Animal Study.

PubMed

Silva, Juliana O; Fernandes, Renata S; Lopes, Sávia C A; Cardoso, Valbert N; Leite, Elaine A; Cassali, Geovanni D; Marzola, Maria Cristina; Rubello, Domenico; Oliveira, Monica C; de Barros, Andre Luis Branco

2016-12-01

Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [ 99m Tc]DOX in 4T1 tumor-bearing BALB/c mice is described. [ 99m Tc]DOX was radiolabeled by direct method. Liposomes were prepared and characterized. [ 99m Tc]DOX was encapsulated into liposomes by freezing and thawing. Circulation time for SpHL-[ 99m Tc]DOX was determined by measuring the blood activity from healthy animals. Biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 24 h after injection. Blood levels of the SpHL-[ 99m Tc]DOX declined in a biphasic manner, with an α half-life of 14.1 min and β half-life of 129.0 min. High uptake was achieved in the liver and spleen, due to the macrophages captured. Moreover, tumor uptake was higher than control tissue, resulting in high tumor-to-muscle ratios, indicating higher specificity for the tumor area. [ 99m Tc]DOX was successfully encapsulated in liposomes. Biodistribution indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. In summary, these results showed the higher accumulation of SpHL-[ 99m Tc]DOX in the tumor area, suggesting selective delivery of doxorubicin into tumor.

Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

NASA Astrophysics Data System (ADS)

Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

2006-12-01

The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

Substitution of the Lys Linker with the β-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

2015-01-01

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg11)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg11)CCMSH (2), RVD-β-Ala-(Arg11)CCMSH (3), RAD-β-Ala-(Arg11)CCMSH (4), NAD-β-Ala-(Arg11)CCMSH (5), and EAD-β-Ala-(Arg11)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their 99mTc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six 99mTc-peptides. 99mTc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these 99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc-4 as an imaging probe. PMID:25290883

Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

Flook, Adam M; Yang, Jianquan; Miao, Yubin

2014-11-13

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

[(99m)Tc(CO)(3)]-radiolabeled bevacizumab: in vitro and in vivo evaluation in a melanoma model.

PubMed

Camacho, Ximena; García, María Fernanda; Calzada, Victoria; Fernández, Marcelo; Chabalgoity, Jose A; Moreno, Maria; Barbosa de Aguiar, Rodrigo; Alonso, Omar; Gambini, Juan Pablo; Chammas, Roger; Cabral, Pablo

2013-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies. To radiolabel bevacizumab with [(99m)Tc(CO)3(OH2)3](+) and evaluate it in vivo and in vitro for melanoma imaging properties. Bevacizumab was radiolabeled with [(99m)Tc(CO)3(OH2)3](+) ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays. We demonstrate that (99m)Tc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of (99m)Tc(CO)3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. (99m)Tc(CO)3-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy. Copyright © 2013 S. Karger AG, Basel.

Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

PubMed

Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P

2015-01-01

Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.

Radiolabelled polymeric IgA: from biodistribution to a new molecular imaging tool in colorectal cancer lung metastases

PubMed Central

Carpenet, Helene; Cuvillier, Armelle; Perraud, Aurélie; Martin, Ophélie; Champier, Gaël; Jauberteau, Marie-Odile; Monteil, Jacques; Quelven, Isabelle

2017-01-01

By radiolabelling monomeric (m) and polymeric (p) IgA with technetium 99m (99mTc), this study assessed IgA biodistribution and tumour-targeting potency. IgA directed against carcinoembryonic antigen (CEA), a colorectal cancer marker, was selected to involve IgA mucosal tropism. Ig was radiolabelled with 99mTc-tricarbonyl after derivatisation by 2-iminothiolane. 99mTc-IgA was evaluated by in vitro analysis. The biodistributions of radiolabelled anti-CEA mIgA, pIgA and IgG were compared in normal mice. Anti-CEA pIgA tumour uptake was studied in mice bearing the WiDr caecal orthotopic graft. IgA radiolabelling was obtained with a high yield, was stable in PBS and murine plasma, and did not alter IgA binding functionality (Kd ≈ 25 nM). Biodistribution studies in normal mice confirmed that radiolabelled pIgA – and to a lesser extent, mIgA – showed strong and fast mucosal tropism and a shorter serum half-life than IgG. In caecal tumour model mice, evaluation of the anti-CEA-pIgA biodistribution showed a high uptake in lung metastases, confirmed by histological analysis. However, no radioactivity uptake increase in the tumoural caecum was discerned from normal intestinal tissue, probably due to high IgA caecal natural tropism. In microSPECT/CT imaging, 99mTc-IgA confirmed its diagnostic potency of tumour in mucosal tissue, even if detection threshold by in vivo imaging was higher than post mortem studies. Contribution of the FcαRI receptor, studied with transgenic mouse model (Tsg SCID-CD89), did not appear to be determinant in 99mTc-IgA uptake. Pre-clinical experiments highlighted significant differences between 99mTc-IgA and 99mTc-IgG biodistributions. Furthermore, tumoural model studies suggested potential targeting potency of pIgA in mucosal tissues. PMID:29156712

Direct comparison of solid-phase gastric emptying times assessed by means of a carbon isotope-labeled sodium acetate breath test and technetium Tc 99m albumin colloid radioscintigraphy in healthy cats.

PubMed

Schmitz, Silke; Götte, Birte; Borsch, Christian; Kunz, Clemens; Failing, Klaus; Neiger, Reto

2014-07-01

To directly compare solid-phase gastric emptying times assessed by means of a [(13)C]sodium acetate breath test ([(13)C]-SABT) and technetium Tc 99m albumin colloid radioscintigraphy ((99m)Tc-ACR) in healthy cats. 12 healthy cats. After ingestion of a test meal containing 50 mg of [(13)C]sodium acetate and 250 MBq of (99m)Tc-albumin colloid, each cat underwent simultaneous [(13)C]-SABT and (99m)Tc-ACR on 2 consecutive days. Breath samples and scintigrams were acquired at 30, 60, 90, 120, 150, 180, 210, 240, 300, 360, 480, and 600 minutes after meal ingestion. Quartiles of gastric emptying (25%, 50%, and 75%) were calculated for breath test analysis by use of the area under the curve of the (13)C:(12)C ratio. Quartiles of gastric emptying times were extrapolated from the scintigraphic findings by beans of nonlinear curve regression analysis. Mean ± SD gastric half-emptying (50%) times obtained with [(13)C]-SABT and (99m)Tc-ACR, were 239 ± 28 minutes and 276 ± 59 minutes, respectively. A 2-way repeated-measures ANOVA revealed that mean gastric emptying times determined with [(13)C]-SABT and (99m)Tc-ACR differed significantly. For the stages of gastric emptying, Pearson correlation between the 2 methods was good at 25% (r = 0.655) and weak at 50% (r = 0.588) and 75% (r = 0.566)of gastric emptying. Results indicated that the [(13)C]-SABT can be a valid alternative to (99m)Tc-ACR in healthy cats; it was easy to perform, was tolerated well by the cats, and had acceptable correlation to scintigraphic findings at gastric emptying of 25%, 50% and 75%. Studies in cats with delayed gastric emptying will be needed to verify the validity of the [(13)C]-SABT.

Synthesis and comparative in vivo evaluation of 99m Tc(CO)3 -labeled PEGylated and non-PEGylated cRGDfK peptide monomers.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Sarma, Haladhar D; Banerjee, Sharmila

2017-03-01

This work aimed at studying the effect of insertion of medium PEG (PEG 7 ) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non-PEGylated analogue. The cRGDfK peptide has thus been derivatized at ε-amino group of lysine by conjugation with N 3 -PEG 7 -COOH/N 3 -CH 2 -COOH to prepare a PEGylated and a non-PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor. Comparative in vivo evaluation of the two 99m Tc(CO) 3 -labeled radiotracers, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 and 99m Tc(CO) 3 -Pra-Tz-PEG 7 -cRGDfK 6, was carried out in C57BL/6 mice bearing α v β 3 -positive melanoma tumors to determine their potential toward targeting integrin α v β 3 receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 ± 0.7% ID/g; 6: 4.1 ± 0.5% ID/g). The two neutral 99m Tc(CO) 3 radiotracers prepared exhibited receptor-mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG 7 unit was accompanied by slower clearance from other organs which resulted in decreased target-to-background ratios. The in vivo kinetics of 99m Tc(CO) 3 -labeled radiotracer, 99m Tc(CO) 3 -Pra-Tz-CH 2 -cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios. © 2016 John Wiley & Sons A/S.

A coupled bimodal SPECT-CT imaging and brain kinetics studies of zolmitriptan-encapsulated nanostructured polymeric carriers.

PubMed

Mandlik, Satish K; Ranpise, Nisharani S; Mohanty, Bhabani S; Chaudhari, Pradip R

2018-06-01

The present investigation deals with preparation and characterization of anti-migraine zolmitriptan (ZMT) nanostructured polymeric carriers for nose to brain drug targeting. The drug-loaded colloidal nanocarriers of ZMT were prepared by modified ionic gelation of cationic chitosan with anionic sodium tripolyphosphate and characterized for particle size, zeta potential, and entrapment efficiency. Further, in order to investigate nose to brain drug targeting, biodistribution, and brain kinetics studies were performed using 99m technetium radiolabeled nanocarriers ( 99m Tc-ZMTNP) in Swiss albino mice. The results were compared with intranasal pure drug solution ( 99m Tc-ZMT) and intravenous nanocarriers ( 99m Tc-ZMTNP). A single photon emission computerized tomography (SPECT) radioimaging studies were also carried out to visualize and confirm brain uptake of nanocarriers. The optimized nanocarriers showed particle size of 161 nm, entrapment efficiency of 80.6%, and zeta potential of + 23.7 mV. The pharmacokinetic parameters, C max , and AUC 0-∞ values for ZMT concentration in the brain expressed as percent radioactivity per gram of brain in intranasal and intravenous route of administration were calculated. The brain C max and AUC 0-∞ values found in three groups, intranasal 99m Tc-ZMTNP, intranasal 99m Tc-ZMT, and intravenous 99m Tc-ZMTNP were (0.427 and 1.889), (0.272 and 0.7157), and (0.204 and 0.9333), respectively. The higher C max values of intranasal 99m Tc-ZMTNP suggests better brain uptake as compared to other routes of administration. The significant higher values of nose to brain targeting parameters namely, drug targeting index (5.57), drug targeting efficiency (557.08%), and nose to brain drug direct transport (82.05%) confirmed drug targeting to brain via nasal route. The coupled bimodal SPECT-CT scintigrams confirm the brain uptake of intranasal 99m Tc-ZMTNP demonstrating major radioactivity accumulation in brain. This study conclusively demonstrated the greater uptake of ZMT-loaded nanocarriers by nose to brain drug targeting, which proves promising drug delivery system.

Differences in the intracellular processing of the radiolabel following the uptake of iodine-125- and technetium-99m-neogalactosyl albumin by the isolated perfused rat liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gore, S.; Morris, A.I.; Gilmore, I.T.

1991-03-01

Neogalactosyl albumin (NGA) is a synthetic ligand to the asialoglycoprotein receptor (hepatic binding protein), which has been proposed as a useful receptor binding radiopharmaceutical for the noninvasive assessment of liver function. We have compared the uptake and intracellular processing of iodine-125- (125I) and technetium-99m- ({sup 99m}Tc) NGA following its administration as a 1-min pulse (147 pmol) to the isolated perfused rat liver. Approximately 40% of a pulse of either {sup 125}I- or {sup 99m}Tc-NGA were taken up first pass by the liver. Of the {sup 125}I taken up by the liver, 82% was released after 15-20 min at the sinusoidalmore » pole of the hepatocyte, predominantly as small molecular weight metabolites. A further 8% of the {sup 125}I-associated radioactivity was secreted as intact NGA into bile by the non-lysosomal (direct) pathway while 6% remained in the liver 1 hr after the pulse. In contrast, of the {sup 99m}Tc taken up by the liver, only 4% reappeared in the perfusate while 40% was secreted into bile by the lysosomal (indirect) pathway and 55% remained in the liver 1 hr after the pulse. Since labeled metabolites of {sup 99m}Tc-NGA do not appear in plasma, this permits kinetic modeling with {sup 99m}Tc-NGA without correction for labeled metabolites. Thus, {sup 99m}Tc-NGA is an excellent candidate as a receptor-binding radiopharmaceutical.« less

Evaluation of hepatic function with (99m)Tc-galactosylated serum albumin scintigraphy in patients with malaria: comparison with (99m)Tc-colloid scintigraphy and liver ultrasonography.

PubMed

Lee, Sang-Woo; Lee, Jaetae; Lee, Deog-Young; Chun, Kyung-Ah; Ahn, Byeong-Cheol; Kang, Young-Mo; Lee, Kyubo

2007-02-01

Malarial parasites injected by the mosquito rapidly target hepatocytes, and hepatomegaly is commonly observed during the progress of the disease in malaria patients. To evaluate the degree of hepatic damage and functional status of hepatocytes in malaria patients, we performed liver scintigraphy using (99m)Tc-galactosylated serum albumin (GSA) prospectively and the findings were compared with those of (99m)Tc-colloid scintigraphy, ultrasonography and clinical results in the same subject. Eight malaria patients (all male, mean age 22 years) confirmed to be infected with Plasmodium vivax underwent (99m)Tc-GSA liver scintigraphy, followed by liver ultrasonography and (99m)Tc-colloid scintigraphy using phytate within 3 days. For hepatocyte scintigraphy, anterior images of cardiac blood-pool and liver were continuously acquired for 30 min after injection of 185 MBq (99m)Tc-GSA (3 mg). In addition to visual interpretation of the images, quantitative measurement of hepatic function was performed with several functional parameters, such as hepatic uptake index (LHL15), blood clearance index (HH15) and modified receptor index (LHL/HH) calculated from the radioactivity of the liver and heart. (99m)Tc-colloid images were assessed and graded visually. Severity of hepatic dysfunction or reticuloendothelial system activation was classified as normal, mild, moderate and severe on GSA or colloid images. Hepatomegaly was observed in five and splenomegaly in seven of the eight patients. Serum levels of transaminase and alkaline phosphatase were mildly elevated in two. Visual assessment of GSA scintigraphy revealed normal findings in all subjects, except for mild increases in size. The mean values of LHL15, HH15 and LHL/HH were 0.928+/-0.014, 0.537+/-0.031 and 1.732+/-0.106, respectively. They were graded as normal in five, and near-normal to mild dysfunction in three subjects. In contrast, (99m)Tc-colloid scintigraphy revealed abnormal findings in all of the subjects, and graded as moderate in three or severe reticuloendothelial system activation in five subjects. Liver ultrasonographic findings were normal for all subjects except mild hepatomegaly. Malaria-induced injury of the hepatocyte is likely to be minimal whereas hepatomegaly is commonly seen during disease process. This suggests that hepatic damage in malarial infection is mainly due to involvement of the reticuloendothelial system. (99m)Tc-GSA scintigraphy can be used in differentiating hepatocellular damage from reticuloendothelial system involvement in patients with infectious disease showing hepatomegaly.

Evaluation of (99m)Tc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT.

PubMed

Li, Fei; Cheng, Teng; Dong, Qingjian; Wei, Rui; Zhang, Zhenzhong; Luo, Danfeng; Ma, Xiangyi; Wang, Shixuan; Gao, Qinglei; Ma, Ding; Zhu, Xiaohua; Xi, Ling

2015-03-01

TMTP1 (NVVRQ) is a novel tumor-homing peptide, which specifically targets tumor metastases, even at the early stage of occult metastasis foci. Fusing TMTP1 to therapeutic peptides or proteins can increase its anti-cancer efficacy both in vivo and in vitro. Here, we labeled TMTP1 with (99m)Tc to evaluate its targeting properties in an ovarian cancer xenograft tumor mouse model and a gastric cancer xenograft mouse model. The invasion ability of SKOV3 and highly metastatic SKOV3.ip cell lines were performed by the Transwell Invasion Assays, and then Rhodamine-TMTP1 was used to detect its affinity to these two cells. Using the co-ligand ethylenediamine-N, N'-diacetic acid (EDDA) and the bifunctional chelator 6-hydrazinonicotinic acid (HYNIC), the TMTP1 peptide was labeled with (99m)Tc. A cell-binding assay was performed by incubating cancer cells with (99m)Tc-HYNIC-TMTP1 with or without an excess dose of cold HYNIC-TMTP1. To evaluate the probe in vivo, nude mice bearing SKOV3, SKOV3.ip and MNK-45 tumor cells were established and subjected to SPECT imaging after injection with (99m)Tc-HYNIC-TMTP1. Ex vivo γ-counting of dissected tissues from the mice was used to evaluate its biodistribution. (99m)Tc-HYNIC-TMTP1 was successfully synthesized. The radiotracer also exhibited high hydrophilicity and excellent stability in vitro and in vivo. It has strong affinity to highly metastatic cancer cell lines but not to poorly metastatic cell lines. After mice were injected with (99m)Tc-HYNIC-TMTP1, non-invasive SPECT imaging detected SKOV3.ip and MNK-45 xenograft tumors but not SKOV3 xenograft tumors. This result can be inhibited by excess HYNIC-TMTP1. The uptake of (99m)Tc-HYNIC-TMTP1 in SKOV3.ip xenograft tumors was 0.182±0.017% ID/g at 2h p.i. with high renal uptake (74.32±15.05% ID/g at 2h p.i.). (99m)Tc-HYNIC-TMTP1 biodistribution and SPECT imaging demonstrated its ability to target highly metastatic tumors. Therefore, metastasis can be non-invasively investigated by SPECT imaging using (99m)Tc-HYNIC-TMTP1. Meanwhile, this radiotracer has some shortages in the low % ID/g of tumors and high accumulation in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

Preclinical Evaluation of RYM1, a Matrix Metalloproteinase-Targeted Tracer for Imaging Aneurysm.

PubMed

Toczek, Jakub; Ye, Yunpeng; Gona, Kiran; Kim, Hye-Yeong; Han, Jinah; Razavian, Mahmoud; Golestani, Reza; Zhang, Jiasheng; Wu, Terence L; Jung, Jae-Joon; Sadeghi, Mehran M

2017-08-01

Matrix metalloproteinases (MMPs) play a key role in abdominal aortic aneurysm (AAA) development. Accordingly, MMP-targeted imaging provides important information regarding vessel wall biology in the course of aneurysm development. Given the small size of the vessel wall and its proximity with blood, molecular imaging of aneurysm optimally requires highly sensitive tracers with rapid blood clearance. To this end, we developed a novel hydrosoluble zwitterionic MMP inhibitor, RYM, on the basis of which a pan-MMP tracer, RYM1, was designed. Here, we describe the development and preclinical evaluation of RYM1 in comparison with RP805, a commonly used pan-MMP tracer in murine models of aneurysm. Methods: The macrocyclic hydroxamate-based pan-MMP inhibitor coupled with 6-hydrazinonicotinamide, RYM1, was synthesized and labeled with 99m Tc. Radiochemical stability of 99m Tc-RYM1 was evaluated by radio-high-performance liquid chromatography analysis. Tracer blood kinetics and biodistribution were compared with 99m Tc-RP805 in C57BL/6J mice ( n = 10). 99m Tc-RYM1 binding to aneurysm and specificity were evaluated by quantitative autoradiography in apolipoprotein E-deficient (apoE -/- ) mice with CaCl 2 -induced carotid aneurysm ( n = 11). Angiotensin II-infused apoE -/- ( n = 16) mice were used for small-animal SPECT/CT imaging. Aortic tissue MMP activity and macrophage marker CD68 expression were assessed by zymography and reverse-transcription polymerase chain reaction. Results: RYM1 showed nanomolar range inhibition constants for several MMPs. 99m Tc-RYM1 was radiochemically stable in mouse blood for 5 h and demonstrated rapid renal clearance and lower blood levels in vivo compared with 99m Tc-RP805. 99m Tc-RYM1 binding to aneurysm and its specificity were shown by autoradiography in carotid aneurysm. Angiotensin II infusion in apoE -/- mice for 4 wk resulted in AAA formation in 36% (4/11) of surviving animals. In vivo 99m Tc-RYM1 small-animal SPECT/CT images showed higher uptake of the tracer in AAA than nondilated aortae. Finally, aortic uptake of 99m Tc-RYM1 in vivo correlated with aortic MMP activity and CD68 expression. Conclusion: The newly developed pan-MMP inhibitor-based tracer 99m Tc-RYM1 displays favorable pharmacokinetics for early vascular imaging and enables specific detection of inflammation and MMP activity in aneurysm. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

PubMed

Hou, X; Tanguay, J; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2016-01-21

In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-01-01

In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Does the Clearance of Inhaled (99m)Tc-Sestamibi Correlate with Multidrug Resistance Protein 1 Expression in the Human Lung?

PubMed

Mohan, Hosahalli K; Routledge, Thomas; Cane, Paul; Livieratos, Lefteris; Ballinger, James R; Peters, Adrien M

2016-09-01

Purpose To examine the relation between the lung elimination rate of inhaled technetium 99m ((99m)Tc)-sestamibi and immunohistochemical expression of bronchopulmonary multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp) and assess the repeatability of the inhaled (99m)Tc-sestamibi clearance technique. Materials and Methods (99m)Tc-sestamibi is a known substrate for P-gp and MRP1, which are established cellular drug efflux transporters. The elimination rate of (99m)Tc-sestamibi from the lungs after inhalation as an aerosol has been hypothesized to be regulated by expression of these transporters. Institutional ethics committee approval was received for this prospective study. Written informed consent was obtained from all participants. The clearance of inhaled (99m)Tc-sestamibi from the lungs of 13 patients due to undergo surgery for primary lung cancer (five of 13) or spontaneous pneumothorax (eight of 13) was estimated after dynamic imaging of the lungs during a period of 40 minutes. The time taken to clear 50% of inhaled sestamibi (T1/2) was compared with a semiquantitative immunohistochemical assessment (grade 0-3) of MRP1 and P-gp expression in the lung by using parametric and nonparametric tests. The study was repeated in five participants to assess the repeatability of the technique by using a Bland Altman analysis method. Results MRP1 expression was seen in 12 of 13 patients, while P-gp expression was seen in only two. The mean (99m)Tc-sestamibi elimination rate was faster in patients (n = 6) with low levels of MRP1 expression (grade 0-1) and mean T1/2 of 105 minutes ± 20 (standard deviation), compared with those with higher levels of MRP1 expression (grade 2-3, n = 7) and mean T1/2 of 149 minutes ± 28 (P = .008). Bland-Altman analysis revealed excellent agreement between test and retest values. Conclusion Inhaled (99m)Tc-sestamibi clearance study is a repeatable technique demonstrating significant correlation with MRP1 expression in the lungs. (©) RSNA, 2016.

Evaluation of lymphoma in a cat using 99mTc-sestamibi.

PubMed

Lenard, Zoe M; Zuber, Richard M; Nicoll, Robert G; O'Hara, Amanda J; Lester, Nola V

2005-01-01

This report describes the evaluation of cutaneous lymphoma in a cat using 99mTc-sestamibi. A mass in the left pes with extension to the left popliteal lymph node was diagnosed as B-cell lymphoma. Thoracic and abdominal radiography and abdominal ultrasound were unremarkable. Scintigraphy using 99mTc-sestamibi confirmed the lesion was confined to the left hind leg, and the leg was amputated. The cat made a full recovery.

Experimental study of /sup 99m/Tc pertechnetate abdominal scans in jejunal intussusception: preliminary results

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, A.E. Jr.; Strecker, E.P.; Miller, F.J. Jr.

1975-07-01

Recent communications have related the diagnosis of small bowel intussusceptions to abnormal accumulations of the radiopharmaceutical /sup 99m/Tc pertechnetate on abdominal scans. Considering the pathophysiological alterations attendant to intussusceptions, we have attempted an experimental model to examine these changes in temporal sequence. This study was initiated to understand the etiology better and to characterize the abnormalities noted on the /sup 99m/Tc pertechnetate abdominal scans.

OAT3-mediated extrusion of the 99mTc-ECD metabolite in the mouse brain

PubMed Central

Kikuchi, Tatsuya; Okamura, Toshimitsu; Wakizaka, Hidekatsu; Okada, Maki; Odaka, Kenichi; Yui, Joji; Tsuji, Atsushi B; Fukumura, Toshimitsu; Zhang, Ming-Rong

2014-01-01

After administration of the 99mTc complex with N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester (99mTc-ECD), a brain perfusion imaging agent, the radioactive metabolite is trapped in primate brain, but not in mouse and rat. Here, we investigate the involvement of metabolite extrusion by organic anion transporter 3 (OAT3), which is highly expressed at the blood–brain barrier in mice, in this species difference. The efflux rate of radioactivity in the cerebrum of Oat3−/− mice at later phase was 20% of that of control mice. Thus, organic anion transporters in mouse brain would be involved in the low brain retention of radioactivity after 99mTc-ECD administration. PMID:24496177

99mTc-D(LPR): A novel retro-inverso peptide for VEGF receptor-1 targeted tumor imaging.

PubMed

Rezazadeh, Farzaneh; Sadeghzadeh, Nourollah; Abedi, Seyed Mohammad; Abediankenari, Saeid

2018-05-31

The aim of this study was to evaluate the ability of D (LPR), a novel retro-inverso peptidomimetic derivative for imaging colon cancer. Two different D (LPR) analogs were designed and compared based on conjugation of HYNIC at peptide's C or N terminal and then labeled with technetium-99m using tricine/EDDA as an exchange coligands. The radiolabeled conjugates were assessed for in vitro stability in saline and serum. The VEGFR-1 and NRP-1 receptors affinity, in vitro internalization and also dissociation Constance was evaluated. SPCET imaging and biodistribution studies were performed in nude mice bearing HT-29 xenograft tumors. Both peptides labeled with technetium-99m in high radiochemical yield (˃97%). Peptide stability studies indicated a high metabolic stability of the radiopeptides in solution and serum. In vitro blocking studies demonstrated specific binding and internalization of [ 99m Tc]Tc-HYNIC-peptides in cultured HUVEC cells. The K d value for 99m Tc-peptide 1 and 99m Tc-peptide 2 were found to be 56.8 ± 12.9 nM and 71.6 ± 17.9 nM respectively. The tumor to muscle ratio was significant at 0.5 and 1 h after injection (4.5 and 4 for 99m Tc-peptide 1 and 4.9 and 4.4 for 99m Tc-peptide 2 at 0.5 and 1 h p.i. respectively). SPECT imaging studies revealed that both radioconjugates had prominent activity accumulation in VEGFR-1 and NRP-1 expressing HT-29 tumors. This study is the first instance of using a radiolabeled retro-inverso peptide for tumor imaging which is a promising tool to improve the performance of fragile peptide probes in vivo as imaging agents and warrant further investigations in other peptide-target systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Prospective Evaluation of (99m)Tc-sestamibi SPECT/CT for the Diagnosis of Renal Oncocytomas and Hybrid Oncocytic/Chromophobe Tumors.

PubMed

Gorin, Michael A; Rowe, Steven P; Baras, Alexander S; Solnes, Lilja B; Ball, Mark W; Pierorazio, Phillip M; Pavlovich, Christian P; Epstein, Jonathan I; Javadi, Mehrbod S; Allaf, Mohamad E

2016-03-01

Nuclear imaging offers a potential noninvasive means of determining the histology of renal tumors. The aim of this study was to evaluate the accuracy of technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography/x-ray computed tomography (SPECT/CT) for the differentiation of oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) from other renal tumor histologies. In total, 50 patients with a solid clinical T1 renal mass were imaged with (99m)Tc-sestamibi SPECT/CT prior to surgical resection. Preoperative SPECT/CT scans were reviewed by two blinded readers, and their results were compared with centrally reviewed surgical pathology data. Following surgery, 6 (12%) tumors were classified as renal oncocytomas and 2 (4%) as HOCTs. With the exception of 1 (2%) angiomyolipoma, all other tumors were renal cell carcinomas (82%). (99m)Tc-sestamibi SPECT/CT correctly identified 5 of 6 (83.3%) oncocytomas and 2 of 2 (100%) HOCTs, resulting in an overall sensitivity of 87.5% (95% confidence interval [CI], 47.4-99.7%). Only two tumors were falsely positive on SPECT/CT, resulting in a specificity of 95.2% (95% CI, 83.8-99.4%). In summary, (99m)Tc-sestamibi SPECT/CT is a promising imaging test for the noninvasive diagnosis of renal oncocytomas and HOCTs. We found that the imaging test (99m)Tc-sestamibi SPECT/CT can be used to accurately diagnose two types of benign kidney tumors. This test may be eventually used to help better evaluate patients diagnosed with a renal tumor. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

99mTc-CXCL8 SPECT to Monitor Disease Activity in Inflammatory Bowel Disease.

PubMed

Aarntzen, Erik H J G; Hermsen, Rick; Drenth, Joost P H; Boerman, Otto C; Oyen, Wim J G

2016-03-01

Inflammatory bowel diseases (IBDs) are defined as chronic relapsing immune-mediated disorders of the gastrointestinal tract. IBD exacerbations are characterized by recruitment of mainly CXCL8 receptor-expressing activated neutrophils into the intestinal wall, leading to severe damage. Considering its chronic relapsing character, accurate and timely diagnosis of an exacerbation is pivotal for early adaptation of the treatment and reduction of the disease burden. However, endoscopic evaluation is invasive and associated with an increased risk of perforation. We previously developed a (99m)Tc-labeled CXCL8 preparation in preclinical models including colitis and clinical studies. In this study, we investigate the accuracy of (99m)Tc-CXCL8 SPECT to detect and localize disease activity in a prospective series of patients with IBD. Thirty patients (15 Crohns disease, 15 ulcerative colitis) participated, and 92 segmental pairs of histology and (99m)Tc-CXCL8 scans were studied. Imaging was performed after injection of 400 MBq of (99m)Tc-CXCL8. Planar and SPECT images of the abdomen were acquired at 30 min and 4 h after the injection. The overall sensitivity and specificity on a per-patient basis for the detection of active disease were 95% and 44% for (99m)Tc-CXCL8 scan and 71% and 70% for endoscopy. The degree of (99m)Tc-CXCL8 accumulation correlated to the degree of neutrophilic influx in affected mucosa. Sensitivity and specificity on a per-segment basis, calculated from the 92 segmental pairs, were 82% and 72%, negative predictive value was 81%, and overall positive predictive value was 74%. Specificity could be increased at the expense of sensitivity using different cutoffs. In 74 segmental pairs, overall sensitivity and specificity for endoscopy were 74% and 85%, positive predictive value was 81%, and negative predictive value was 79%. (99m)Tc-CXCL8 SPECT provides a novel imaging technique to target neutrophil recruitment to the intestinal wall, especially in moderate to severe exacerbations of IBD. Further validation studies are warranted to potentiate (99m)Tc-CXCL8 SPECT as a biomarker to scale up or step down treatment with immune-modulating drugs in a personalized fashion. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Calculation of therapeutic activity of radioiodine in Graves' disease by means of Marinelli's formula, using technetium (99mTc) scintigraphy.

PubMed

Szumowski, Piotr; Mojsak, Małgorzata; Abdelrazek, Saeid; Sykała, Monika; Amelian-Fiłonowicz, Anna; Jurgilewicz, Dorota; Myśliwiec, Janusz

2016-12-01

The therapeutic activity of 131 I administered to patients with Graves' disease can be calculated by means of Marinelli's formula. The thyroidal iodine uptake ( 131 IU max ) needed for the calculation is usually determined with the use of 131 I. The purpose of the paper was to estimate 131 IU max on the basis of technetium uptake in the thyroid at 20 min ( 99m TcU 20min ). Eighty patients suffering from Graves' disease were qualified for radioiodine therapy with measurement of fT 4 , fT 3 , thyroid-stimulating hormone and its receptor (TRAb). Prior to the treatment, all the patients were euthyroid. 131 IU max for each patient was determined according to the levels of 131 I after 24 h ( 131 IU 24h ), while effective half-life (T eff ) according to the measurements of 131 IU 24h and 131 I uptake after 48 h ( 131 IU 48h ). Additionally, on the day before measuring 131 IU 24h , 99m TcU 20min was calculated for each patient. It was demonstrated that there existed a correlation, with statistical significance at p < 0.05, between the following pairs of values: TRAb and 131 IU 24h , TRAb and 99m TcU 20min , and 99m TcU 20min and 131 IU 24h . The interdependence between 131 IU 24h and 99m TcU 20min at the level of significance p < 0.05 is described by the following algorithms: 131 IU 24h  = 17.72 × ln ( 99m TcU 20min ) + 30.485, if TRAb < 10 IU/ml, and 131 IU 24h  = 18.03 × ln ( 99m TcU 20min ) + 38.726, if TRAb > 10 IU/ml. It is possible to predict thyroid iodine uptake 131 IU 24h in Graves' disease on the basis of measuring the uptake of 99m TcU 20min . This shortens the time necessary for diagnosis and enables the calculation of 131 I activity using Marinelli's formula.

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional 99mTc-HSAD multigated cardiac pool imaging.

PubMed

Yamazaki, J; Naitou, K; Ishida, S; Uno, N; Saisho, K; Munakata, T; Morishita, T; Takano, M; Yabe, Y

1997-05-01

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging. 99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from 99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 +/- 36.0 ml vs. 198.7 +/- 39.1 ml, r = 0.791, p < 0.001; LVESV: 91.6 +/- 44.5 ml vs. 93.3 +/- 41.3 ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement. 3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Evaluation of a 99mTc-labeled AnnexinA5 variant for non-invasive SPECT imaging of cell death in liver, spleen and prostate.

PubMed

Greupink, Rick; Sio, Charles F; Ederveen, Antwan; Orsel, Joke

2009-12-01

We investigate radio-labeling and pharmacokinetics of a new AnnexinA5 variant (HYNIC-cys-AnxA5) and then assess its utility for the non-invasive detection of cell death in liver, spleen and prostate. AnnexinA5 binds to phosphatidylserine expressed on the surface of apoptotic and necrotic cells. Contrary to other AnnexinA5 variants, the new cys-AnxA5 allows for site-specific conjugation of a hydrazinonicotinamide-maleimide moiety and subsequent radio-labeling with (99m)Tc at a position not involved in the AnxA5-phosphatidylserine interaction. Distribution of (99m)Tc-HYNIC-cys-AnxA5 was studied in rats, both invasively and via SPECT/CT. Cycloheximide was used to induce cell death in liver and spleen, whereas apoptosis in the prostate was induced by castration. HYNIC-cys-AnxA5 was efficiently and reproducibly labeled with (99m)Tc. Blood clearance of radioactivity after iv-injection was adequately described by a two-compartment model, the renal cortex representing the main site of accumulation. Cycloheximide treatment resulted in increased accumulation of intravenous-injected (99m)Tc-HYNIC-cys-AnxA5 in liver and spleen over controls, which correlated well with TUNEL staining for cell death in corresponding tissue sections. However, the increase in TUNEL-positive prostate epithelial cells observed following castration was not paralleled by greater (99m)Tc-HYNIC-cys-AnxA5 accumulation. (99m)Tc-HYNIC-cys-AnxA5 appears a suitable tracer for assessment of cell death in liver and spleen, but not prostate.

Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves' ophthalmopathy.

PubMed

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC) to detect clinical stage of Graves' ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves' ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of (99m)Tc-TOC. The (99m)Tc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital (99m)Tc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital (99m)Tc-TOC scintigraphy is a feasible technique to estimate the Graves' ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination.

Clinical indications to the use of (99m)Tc-EDDA/HYNIC-TOC to detect somatostatin receptor-positive neuroendocrine tumors.

PubMed

Parisella, M G; Chianelli, M; D'Alessandria, C; Todino, V; Mikolajczak, R; Papini, E; Dierckx, R A; Scopinaro, F; Signore, A

2012-02-01

The aim of this study was to define, retrospectively, the utility to perform (99m)Tc-EDDA/HYNIC-Tyr3-octreotide ((99m)Tc-EDDA/HYNIC-TOC) scan in patients with NET. We studied 50 consecutive patients affected by different types of NET and divided in two groups. Group 1: 34 patients with known lesions in which (99m)Tc-EDDA/HYNIC-TOC was performed for staging, characterisation or to choose the appropriate treatment. Group 2: 16 patients suspected of having NET or in follow up after surgery. Patients were injected with 370 MBq of (99m)Tc-EDDA/HYNIC-Tyr3-octreotide and whole-body and SPET images acquired 2-3 hours after injection. Overall, 29 patients (58%) had a positive scan, with a sensitivity, specificity and accuracy of 70.3%, 76.9% and 72%, respectively (78.1%, 50% and 76.5%, in group 1 and 20%, 81.2%, 62.5% in group 2). In patients from group 1 (99m)Tc-HYNIC-TOC scintigraphy showed a concordance of 68% with another imaging procedure and in 9 patients revealed a greater number of lesions. In the second group, false negative results were especially found in patients with medullary thyroid cancer with negative radiological findings and elevated calcitonin. In conclusion, (99m)Tc-EDDA/HYNIC-TOC is highly indicated for in vivo histological characterization of known NET lesions, previously identified by other imaging modalities or biopsy, to plan appropriate therapy especially for patients with inoperable disease. In patients with only biochemical suspicion of NET and in those with negative markers, this scintigraphy does not significantly modify the clinical management.

Radiochemical studies of 99mTc complexes of modified cysteine ligands and bifunctional chelating agents.

PubMed

Pillai, M R; Kothari, K; Banerjee, S; Samuel, G; Suresh, M; Sarma, H D; Jurisson, S

1999-07-01

The synthesis of four novel ligands using the amino-acid cysteine and its ethyl carboxylate derivative is described. The synthetic method involves a two-step procedure, wherein the intermediate Schiff base formed by the condensation of the amino group of the cysteine substrate and salicylaldehyde is reduced to give the target ligands. The intermediates and the final products were characterized by high resolution nuclear magnetic resonance spectroscopy. Complexation studies of the ligands with 99mTc were optimized using stannous tartrate as the reducing agent under varying reaction conditions. The complexes were characterized using standard quality control techniques such as thin layer chromatography, paper electrophoresis, and paper chromatography. Lipophilicities of the complexes were estimated by solvent extraction into chloroform. Substantial changes in net charge and lipophilicity of the 99mTc complexes were observed on substituting the carboxylic acid functionality in ligands I and II with the ethyl carboxylate groups (ligands II and IV). All the ligands formed 99mTc complexes in high yield. Whereas the complexes with ligands I and II were observed to be hydrophilic in nature and not extractable into CHCl3, ligands III and IV resulted in neutral and lipophilic 99mTc complexes. The 99mTc complex with ligand II was not stable and on storage formed a hydrophilic and nonextractable species. The biodistribution of the complexes of ligands I and II showed that they cleared predominantly through the kidneys, whereas the complexes with ligands III and IV were excreted primarily through the hepatobiliary system. No significant brain uptake was observed with the 99mTc complexes with ligands III and IV despite their favorable properties of neutrality, lipophilicity, and conversion into a hydrophilic species. These ligands offer potential for use as bifunctional chelating agents.

Variable uptake feature of focal nodular hyperplasia in Tc-99m phytate hepatic scintigraphy/single-photon emission computed tomography-A parametric analysis.

PubMed

Hsu, Yu-Ling; Chen, Yu-Wen; Lin, Chia-Yang; Lai, Yun-Chang; Chen, Shinn-Cherng; Lin, Zu-Yau

2015-12-01

Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9-7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors. Copyright © 2015. Published by Elsevier Taiwan.

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PubMed

Giovanella, L; Campenni, A; Treglia, G; Verburg, F A; Trimboli, P; Ceriani, L; Bongiovanni, M

2016-06-01

To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

Morphobiochemical diagnosis of acute trabecular microfractures using gamma correction Tc-99m HDP pinhole bone scan with histopathological verification.

PubMed

Bahk, Yong-Whee; Hwang, Seok-Ha; Lee, U-Young; Chung, Yong-An; Jung, Joo-Young; Jeong, Hyeonseok S

2017-11-01

We prospectively performed gamma correction pinhole bone scan (GCPBS) and histopathologic verification study to make simultaneous morphobiochemical diagnosis of trabecular microfractures (TMF) occurred in the femoral head as a part of femoral neck fracture.Materials consisted of surgical specimens of the femoral head in 6 consecutive patients. The specimens were imaged using Tc-99m hydroxymethylene diphosphonate (HDP) pinhole scan and processed by the gamma correction. After cleansing with 10% formalin solution, injured specimen surface was observed using a surgical microscope to record TMF. Morphological findings shown in the photograph, naive pinhole bone scan, GCPBS, and hematoxylin-eosin (H&E) stain of the specimen were reciprocally correlated for histological verification and the usefulness of suppression and enhancement of Tc-99m HDP uptake was biochemically investigated in TMF and edema and hemorrhage using gamma correction.On the one hand, GCPBS was able to depict the calcifying calluses in TMF with enhanced Tc-99m HDP uptake. They were pinpointed, speckled, round, ovoid, rod-like, geographic, and crushed in shape. The smallest callus measured was 0.23 mm in this series. On the other hand, GCPBS biochemically was able to discern the calluses with enhanced high Tc-99m HDP uptake from the normal and edema dipped and hemorrhage irritated trabeculae with washed out uptake.Morphobiochemically, GCPBS can clearly depict microfractures in the femoral head produced by femoral neck fracture. It discerns the microcalluses with enhanced Tc-99m HDP uptake from the intact and edema dipped and hemorrhage irritated trabeculae with suppressed washed out Tc-99m HDP uptake. Both conventional pinhole bone scan and gamma correction are useful imaging means to specifically diagnose the microcalluses naturally formed in TMF.

99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel disease.

PubMed

Peacock, Kenneth; Porn, Ute; Howman-Giles, Robert; O'Loughlin, Edward; Uren, Roger; Gaskin, Kevin; Dorney, Stuart; Kamath, Ramanand

2004-02-01

99mTc-Labeled white cell scintigraphy (WCS) has been used for the investigation of inflammatory bowel disease (IBD) in adults, but data on children are limited. The most common agent used is (99m) Tc-hexamethylpropyleneamine oxime (HMPAO); however, this agent has limitations. In a retrospective study, we assessed the use of (99m)Tc-stannous colloid WCS for the initial evaluation of children with suspected IBD. Diagnostic, endoscopic, and contrast radiography results were retrospectively collected from the medical records. Two experienced nuclear physicians unaware of the patient data interpreted the WCS results, with agreement reached by consensus. Statistical analysis was performed on the ability of WCS to detect active disease and localize it topographically and on a comparison of diagnostic methods, using a combination of clinical features and endoscopy as the reference standard. Between 1996 and 1999, 64 patients (35 male and 29 female; mean age, 12.5 y; age range, 2-19 y) had WCS performed, with IBD subsequently diagnosed in 34 patients. (99m)Tc-Stannous colloid WCS had an 88% sensitivity, 90% specificity, and 8.8 likelihood ratio for initial investigation of IBD. Agreement was poor for topographic localization of disease. Small-bowel series had a 75% sensitivity, 50% specificity, and 1.5 likelihood ratio for detecting endoscopic disease of the terminal ileum and proximal colon. Our results confirm that WCS is a useful imaging technique for the initial evaluation of patients with suspected IBD. (99m)Tc-Stannous colloid had results at least comparable to those of other WCS agents, and in children, (99m)Tc-stannous colloid WCS should be preferred in view of lower cost, shorter preparation time, and the smaller blood volumes required.

Efficacy of 99mTc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves’ ophthalmopathy

PubMed Central

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) to detect clinical stage of Graves’ ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves’ ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of 99mTc-TOC. The 99mTc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital 99mTc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital 99mTc-TOC scintigraphy is a feasible technique to estimate the Graves’ ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination. PMID:23133815

Bone scintigraphy of the aged patient. 1. /sup 99m/Tc-polyphosphate bone scintigraphy (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, M.; Chiba, K.; Tanno, M.

Application and evaluation of a new bone-seeking radiopharmaceuticai, / sup 99m/Tc-polyphosphate are reported. Analysis of the image by digital color display data analyzer (Phosdac) was performed. The subjects of the study were cases at Tokyo Metropolitan Geriatric Hospital ranging from 63 to 85 years old with several kinds of bone diseases. Polyphosphate kits (Diagnostic Isotopes, Inc.) were used to prepare /sup 99m/Tc, and a Rho/gamma HP gamma-camera was used for scintigraphy. The images obtained were analyzed by Phosdac to obtain clear image of the bone system. In the final preparation, presence of approximately 30% of free /sup 99m/Tc was noticedmore » by paper chromatography. /sup 99m/Tc- polyphosphate was cleared from the blood with a half time of about 60 min. Urinary excretion proved to be 40 to 60% within 24 hrs. The bone system was visualized rather clearly with high accumulation of the label in the diseased region in spite of the fact that geriatric cases had marked general osteoporotic tendencies. In some cases, ribs were clearly visualized, and different information from that of x-ray was obtained by scanning images. Data processing by Phosdac increased diagnostic accuracy by enhancing the difference of the density of the image as well as eliminating the background caused by free /sup 99m/TcO/sub 4/. In conclusion, /sup 99m/Tc-polyphosphate was proved to be useful for bone scanning in geriatric cases. A digital color display data analyzer was successfully applied for the processing of the original data. (auth)« less

Radionuclidic purity measurements for cyclotron-produced 99mTc via 100Mo(p,2n) at 18 MeV

NASA Astrophysics Data System (ADS)

Buckley, K.; Tanguay, J.; Hou, X.; Stothers, L.; Vuckovic, M.; Frantzen, K.; Cockburn, N.; Corsaut, J.; Dodd, M.; Goodbody, A.; Hanemaayer, V.; Hook, B.; Klug, J.; Kovacs, M.; Kumlin, J.; McDiarmid, S.; McEwan, J.; Prato, F.; Ruddock, P.; Valiant, J.; Zeisler, S.; Ruth, T.; Celler, A.; Benard, F.; Schaffer, P.

2017-05-01

The radionuclidic purity of cyclotron-produced 99mTc has been measured by gamma ray spectroscopy and compared to the results of a quick release test modeled after the molybdenum breakthrough test performed on generator-derived 99mTc. Excellent radionuclidic purity is reported for samples produced at BCCA during our clinical trial. The quick release test results agree well with the gamma ray analysis.

Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

PubMed Central

Pereira, Edgar; do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; Di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

2017-01-01

A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners. PMID:28211920

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

PubMed

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Omer

2013-12-01

The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. None declared.

In Vitro/In Vivo Evaluation of Radiolabeled [(99m)Tc(CO)3](+)-Hydroxyurea and Fluorescein Isothiocyanate-Hydroxyurea.

PubMed

Yilmaz, Baris; Teksoz, Serap; Kilcar, Ayfer Yurt; Ucar, Eser; Ichedef, Cigdem; Medine, Emin Ilker; Ari, Kadir

2016-02-01

The aim of current study is to examine hydroxyurea (HU), which is an antineoplastic drug used for the treatment of leukemia, sickle-cell disease, HIV, psoriasis, thrombocythemia, and various neoplastic diseases in two aspects. The active ingredient hydroxyurea was obtained by purification of the capsule form drug, commercially named as HYDREA. Then, [(99m)Tc(CO)3](+)core radiolabeling with HU was performed as first aspect. Quality control studies of (99m)Tc(CO)3-HU complex were performed by thin-layer radiochromatography and high-performance liquid radiochromatography methods. The results demonstrated that the radiolabeling yield was quite high (98.43% ± 2.29%). Also, (99m)Tc(CO)3-HU complex has good stability during the 24-hour period. Biological behavior of (99m)Tc(CO)3-HU complex is evaluated by biodistribution studies on Wistar Albino rats. Fluorescein isothiocyanate (FITC) labeling of HU was performed as second aspect. Fluorometric evaluation of binding efficacy and fluorescence imaging studies on MCF7 and Hela cell lines were carried out. It was thought that the knowledge achieved in this study would contribute to using (99m)Tc(CO)3-HU complex as an imaging agent, which inhibits the DNA synthesis selectively, by inhibiting ribonucleotide reductase enzyme. It was observed that FITC-HU has noteworthy incorporation on both cell lines.

99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

PubMed

Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

2017-05-15

The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

Measurement of pulmonary epithelial permeability with /sup 99m/Tc-DTPA aerosol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coates, G.; O'Brodovich, H.

1986-10-01

The rate at which inhaled aerosol of /sup 99m/Tc-diethylenetriamine pentaacetate (DTPA) leaves the lung by diffusion into the vascular space can be measured with a gamma camera or simple probe. In normal humans, /sup 99m/Tc-DTPA clears from the lung with a half time of about 80 minutes. Many acute and chronic conditions that alter the integrity of the pulmonary epithelium cause an increased clearance rate. Thus cigarette smoking, alveolitis from a variety of causes, adult respiratory distress syndrome (ARDS), and hyaline membrane disease (HMD) in the infant have all been shown to be associated with rapid pulmonary clearance of /supmore » 99m/Tc-DTPA. Rapid clearance is also promoted by increased lung volume and decreased surfactant activity. Although the mechanism of increased clearance in pathological states is not known, the /sup 99m/Tc-DTPA lung-clearance technique has great potential clinically, particularly in patients at risk from ARDS and HMD and in the diagnosis and follow-up of alveolitis. 58 references.« less

Update on radionuclide imaging in hepatobiliary disease. [/sup 99m/Tc-labelled acetanilide iminodracetic acid analogues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthall, L.

1981-05-01

The recent introduction of technetium Tc 99m-labeled acetanilide iminodiacetic acid (/sup 99m/Tc-IDA) analogues has facilitated the clincal study of the bile flow pathways. A variety of /sup 99m/Tc-IDA derivaties are under investigation. Basically all are metabolized by the hepatocyte and immediately thereafter excreted unconjugated into the biliary tract. Of the various derivatives tested, e.g., dimethyl (lidofenin), diethyl, paraisopropyl (iprofenin), parabutyl (butilfenin), and diisopropyl (disofenin), the last named is the best universal agent at this time. By serial liver imaging the patency of the cystic duct and the integrity of altered cholangiointestinal anatomy can be assessed, leakage of bile and gastricmore » reflux can be disclosed, and medical and surgical jaundice can be distinguished.« less

An improved 99mTc-HYNIC-(Ser)3-LTVSPWY peptide with EDDA/tricine as co-ligands for targeting and imaging of HER2 overexpression tumor.

PubMed

Khodadust, Fatemeh; Ahmadpour, Sajjad; Aligholikhamseh, Nazan; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-01-20

Overexpression of human epidermal receptor 2 (HER2) has given the opportunity for targeting and delivering of imaging radiotracers. The aim of this study was to evaluate the 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY peptide for tumor targeting and imaging of tumor with overexpression of HER2. The HYNIC-(Ser) 3 -LTVSPWY was labeled with 99m Tc in presence of EDDA/tricine mixture as co-ligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular specific binding and tumor targeting. The high radiochemical purity of 99m Tc-HYNIC (EDDA/tricine)-(Ser) 3 -LTVSPWY was obtained to be 99%. It exhibited high stability in normal saline and human serum. In HER2 binding affinity study, a significant reduction in uptake of radiolabeled peptide (7.7 fold) was observed by blocking SKOV-3 cells receptors with unlabeled peptide. The K D and B max values for this radiolabeled peptide were determined as 3.3 ± 1.0 nM and 2.9 ± 0.3 × 10 6 CPM/pMol, respectively. Biodistribution study revealed tumor to blood and tumor to muscle ratios about 6.9 and 4 respectively after 4 h. Tumor imaging by gamma camera demonstrated considerable high contrast tumor uptake. This developed 99m Tc-HYNIC-(Ser) 3 -LTVSPWY peptide selectively targeted on HER2 tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m Tc-HYNIC-(EDDA/tricine)-(Ser) 3 -LTVSPWY is much better than previously reported radiolabeled peptide as 99m Tc-CSSS-LTVSPWY for HER2 overexpression tumor targeting and imaging. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Small Column Testing of Superlig 639 for Removal of 99Tc from Hanford Tank Waste Envelope C (Tank 241-AN-107)

DOE Office of Scientific and Technical Information (OSTI.GOV)

DL Blanchard; DE Kurath; BM Rapko

The current BNFL Inc. flow sheet for pretreating Hanford High-Level tank wastes includes the use of Superlig(reg.sign)639 (SL-639) in a dual column system for removing technetium-99 ({sup 99}Tc) from the aqueous fraction of the waste. This sorbent material has been developed and supplied by IBC Advanced Technologies, Inc., American Fork, UT. This report documents the results of testing the SL-639 sorbent with diluted waste [Na{sup +}] {approx} 5 M from Tank 241-AN-107 (an Envelope C waste, abbreviated AN-107) at Battelle Northwest Laboratories (BNW). The equilibrium behavior was assessed with batch contacts between the sorbent and the waste. Two AN-107 samplesmore » were used: (1) an archived sample from previous testing and (2) a more recent sample collected specifically for BNFL. A portion of the archive sample and all of the BNFL sample were treated to remove Sr-90 and transuranic elements (TRU). All samples had also been Cs decontaminated by ion exchange (IX), and were spiked with a technetium-95m ({sup 95m}Tc) pertechnetate tracer, {sup 95m}TcO{sub 4}{sup -}.The TcO{sub 4}{sup -} and total Tc K{sub d} values, assumed equal to the {sup 95m}Tc and {sup 99}Tc K{sub d}'s, respectively, are shown in Table S1. Values are averages of duplicates, which showed significant scatter. The total Tc K{sub d} for the BNFL sample is much lower than the TcO{sub 4}{sup -}, indicating that a large fraction of the {sup 99}Tc is not pertechnetate.« less

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forman, M.B.; Sandler, M.P.; Sacks, G.A.

1983-03-01

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

PubMed

Lai, Kunbei; Jin, Chenjin; Tu, Shu; Xiong, Yunfan; Huang, Rui; Ge, Jian

2014-07-01

The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05). Intravitreal injection of (99)Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that (99)Tc-MDP has therapeutic potential for CNV related diseases.

Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

PubMed

Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

2018-05-20

Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

PubMed Central

Li, Yanli; Hu, Yan; Xiao, Jie; Liu, Guobing; Li, Xiao; Zhao, Yanzhao; Tan, Hui; Shi, Hongcheng; Cheng, Dengfeng

2016-01-01

SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy. PMID:27649935

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerson, M.C.; Millard, R.W.; McGoron, A.J.

1994-10-01

We postulated that {sup 99m}Tc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of {sup 99m}Tc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for {sup 99m}Tcmore » activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10mCi of {sup 99m}Tc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following k{sup 99m}Tc-Q3 injection. Microsphere blood flow and endocardial biopsies (n - 6 dogs) were performed at 30, 60, 120 and 240 min following {sup 99m}TcQ3 injection. 31 refs., 9 figs., 1 tab.« less

Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol☆

PubMed Central

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

2014-01-01

Lymphoseek is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node (SLN) mapping. We conducted a clinical trial which measured the injection site clearance and sentinel lymph node accumulation after a single intradermal injection of Lymphoseek or unfiltered [99mTc]sulfur colloid (TcSC) using a “2-day” protocol for SLN mapping of breast cancer. Eleven patients with breast cancer participated in this study. Five patients received an intradermal administration of 1.0 nmol of 99mTc-labeled Lymphoseek; SLN mapping was performed on four subjects within 19 to 27 h. Six subjects received an intradermal administration of TcSC; SLN mapping was performed on five subjects within 18 to 26 h. Lymphoseek exhibited a significantly (P<.001) faster injection site clearance than TcSC. The mean Lymphoseek clearance half-time was 2.18±1.09 h compared to 57.4±92.8 h for TcSC. The mean sentinel lymph node uptake of Lymphoseek (1.5±1.7%) and TcSC (3.5±3.1%) was statistically equivalent (P=.213). When an intradermal injection is employed, Lymphoseek demonstrated faster injection site clearance than unfiltered [99mTc]sulfur colloid and persistent SLN accumulation for at least 24 h. PMID:19647175

Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer by 99mTc-MIBI SPECT/CT; a pilot study.

PubMed

Tangjaturonrasme, Napadon; Vasavid, Pataramon; Sombuntham, Premsuda; Keelawat, Somboon

2013-06-01

Papillary thyroid cancer has a high prevalence of cervical nodal metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary thyroid cancer Fifteen patients were performed 99Tc-MlBI SPECT/CT pre-operatively. Either positive pathological report of neck dissection or positive post-treatment I-131 whole body scan with SPECT/CT of neck was concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI SPECT/CT were analyzed. The PPV NPV and accuracy were 80%, 88.89%, and 85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes groups correctly in most cases when compared with pathological results. However the authors found one false positive case with caseating granulomatous lymphadenitis and one false negative case with positive post-treatment 1-131 whole body scan with SPECT/CT of neck on cervical nodes zone II and IV CONCLUSION: 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of cervical nodal involvement in patients with papillary thyroid cancer without the need of using iodinated contrast that may complicate subsequence 1-131 treatment. However, false positive result in granulomatous inflammatory nodes should be aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good result when compared with previous study of CT or MRI imaging. The comparative study between different imaging modality and the extension of neck dissection according to MIBI result seems interesting.

Factors affecting the sensitivity of Tc-99m methoxyisobutylisonitrile dual-phase parathyroid single photon emission computed tomography in primary hyperparathyroidism.

PubMed

Araz, Mine; Çayir, Derya; Erdoğan, Mehmet; Uçan, Bekir; Çakal, Erman

2017-02-01

The aim of this study was to investigate the effects of thyroid diseases and regularly used medications on the sensitivity of Tc-99m methoxyisobutylisonitrile (MIBI) dual-phase parathyroid single photon emission computed tomography (SPECT) and to define indicatives of the result of the study. Overall, 218 primary hyperparathyroidism patients (190 women, 28 men, mean age: 57±14 years) with thyroid-parathyroid ultrasonography and Tc-99m MIBI dual-phase parathyroid SPECT were retrospectively enrolled. Patients were divided as follows: a positive SPECT group [119 (54.6%) patients] and a negative SPECT group [99 (45.4%) patients]. The effects of thyroid diseases and use of calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, oral antidiabetics, thyroid hormone preparates, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors on the sensitivity of Tc-99m MIBI dual-phase parathyroid SPECT were investigated. The frequency of NSAID usage was higher in the negative scan group (P<0.001). No significant difference was detected in terms of coexisting thyroid disease or usage of other medications. Overall sensitivity, specificity, positive, and negative predictive value of Tc-99m MIBI dual-phase parathyroid SPECT were calculated to be 89.6, 92.5, 94.1, and 86.9%. The sensitivity was low only in nonsteroidal anti-inflammatory drug users (75.6%) compared with nonusers (96.5%). Logistic regression showed that ultrasonography was indicative of a positive scan and the possibility of a negative result was increased by regular usage of nonsteroid anti-inflammatory drugs (odds ratio: 0.262, confidence interval: 0.128-0.538; P<0.001) CONCLUSION: Among various drug groups, NSAIDs may decrease the sensitivity of Tc-99m MIBI SPECT and, provided that these novel data are supported by other studies, patient preparation may be modified to stop NSAIDs before Tc-99m MIBI dual-phase parathyroid SPECT.

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high efficiency SPECT

PubMed Central

Brodov, Yafim; Fish, Mathews; Rubeaux, Mathieu; Otaki, Yuka; Gransar, Heidi; Lemley, Mark; Gerlach, Jim; Berman, Daniel; Germano, Guido; Slomka, Piotr

2016-01-01

Background Ejection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT. Methods Fifty patients (mean age 69 y) undergoing regadenoson same-day rest (8–11 mCi)/stress (32–42mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started one min after sequential intravenous regadenoson 0.4mg and Tc-99m injection, and was composed of five 2 min supine gated acquisitions followed by two 4 min supine and upright images. Ischemic total perfusion deficit (ITPD) ≥ 5 % was considered as significant ischemia. Results Significantly lower mean EF reserve was obtained in the 5th and 9th min after regadenoson bolus in patients with significant ischemia versus patients without (5th min: −4.2 ± 4.6% vs. 1.3 ± 6.6%, p = 0.006; 9th min: −2.7 ± 4.8% vs. 2.0 ± 6.6%, p = 0.03). Conclusions Negative EF reserve obtained between 5th and 9th min of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of myocardial stunning with Tc-99m HE-SPECT. PMID:27387521

Quantitation of left ventricular ejection fraction reserve from early gated regadenoson stress Tc-99m high-efficiency SPECT.

PubMed

Brodov, Yafim; Fish, Mathews; Rubeaux, Mathieu; Otaki, Yuka; Gransar, Heidi; Lemley, Mark; Gerlach, Jim; Berman, Daniel; Germano, Guido; Slomka, Piotr

2016-12-01

Ejection fraction (EF) reserve has been found to be a useful adjunct for identifying high risk coronary artery disease in cardiac positron emission tomography (PET). We aimed to evaluate EF reserve obtained from technetium-99m sestamibi (Tc-99m) high-efficiency (HE) SPECT. Fifty patients (mean age 69 years) undergoing regadenoson same-day rest (8-11 mCi)/stress (32-42 mCi) Tc-99m gated HE SPECT were enrolled. Stress imaging was started 1 minute after sequential intravenous regadenoson .4 mg and Tc-99m injections, and was composed of five 2 minutes supine gated acquisitions followed by two 4 minutes supine and upright images. Ischemic total perfusion deficit (ITPD) ≥5 % was considered as significant ischemia. Significantly lower mean EF reserve was obtained in the 5th and 9th minute after regadenoson bolus in patients with significant ischemia vs patients without (5th minute: -4.2 ± 4.6% vs 1.3 ± 6.6%, P = .006; 9th minute: -2.7 ± 4.8% vs 2.0 ± 6.6%, P = .03). Negative EF reserve obtained between 5th and 9th minutes of regadenoson stress demonstrated best concordance with significant ischemia and may be a promising tool for detection of transient ischemic functional changes with Tc-99m HE-SPECT.

Minimally invasive radioguided parathyroid surgery using low-dose Tc-99m-MIBI - comparison with standard high dose.

PubMed

Jangjoo, Ali; Sadeghi, Ramin; Mousavi, Zohreh; Mohebbi, Masoud; Khaje, Mahtab; Asadi, Mehdi

2017-01-01

Surgery remains the most effective treatment for primary hyperparathyroidism (PHPT). Minimally invasive radioguided parathyroidectomy (MIRP) is a common technique for detecting and excising abnormal parathyroid glands. The aim of this study was to compare injections of low-dose and high-dose (99m) Tc methoxy isobutyl isonitrile (MIBI) for intraoperative localisation of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). Thirty patients with PHPT and a preoperative diagnosis of parathyroid adenoma were enrolled between 2010 and 2012. They were considered as Group B and underwent MIRP using 5 mCi Tc-99m MIBI, and their perioperative data were compared with twenty patients treated with conventional 20 mCi Tc-99m MIBI previously (Group A). Group A was made up of 20 patients (mean age, 41.55 years; 14 women and 6 men), and group B included 30 patients (mean age, 40.43 years; 19 women and 11 men). The mean serum parathyroid hormone (PTH) and calcium values were recorded pre- and postoperatively. The mean follow-up period for the patients in the two groups was 18.4 and 16.5 months, respectively. Pre-operative evaluation demonstrated that the groups were statistically similar. Intraoperative data and success rate of surgery showed no difference between the two groups. No significant complication was detected after surgeries and no recurrence happened in either of the two groups during the follow-up period. A new protocol of MIRP using low doses of Tc-99m-MIBI resulted in an excellent success rate. Comparing results of the study, we conclude that low-dose Tc-99m-MIBI may be preferred for identification of parathyroid adenomas intraoperatively by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose Tc-99m-MIBI.

Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

PubMed

Dias, Carla Roberta; Jeger, Simone; Osso, João Alberto; Müller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

2011-01-01

The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology). The native format of the antibody (RTX(wt)) as well as a reduced form (RTX(red)) was labeled with (99m)Tc/(188)Re(CO)(3). The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. The radiolabeling efficiency and kinetics of RTX(red) were superior to that of RTX(wt) ((99m)Tc: 98% after 3 h for RTX(red) vs. 70% after 24 h for RTX(wt)). (99m)Tc(CO)(3)-RTX(red) was used without purification for in vitro and in vivo studies whereas (188)Re(CO)(3)-RTX(red) was purified to eliminate free (188)Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 °C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of (99m)Tc(CO)(3)-RTX(red) but not with pre-purified (188)Re(CO)(3)-RTX(red). Both conjugates revealed high binding affinity to the CD20 antigen (K(d) = 5-6 nM). Tumor uptake of (188)Re(CO)(3)-RTX(red) was 2.5 %ID/g and 0.8 %ID/g for (99m)Tc(CO)(3)-RTX(red) 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for (99m)Tc(CO)(3)-RTX(red) and for (188)Re(CO)(3)-RTX(red) 0.5 and 0.5 (24 h pi). Rituximab could be directly and stably labeled with the matched pair (99m)Tc/(188)Re using the IsoLink technology under retention of the biological activity. Labeling kinetics and yields need further improvement for potential routine application in radioimmunodiagnosis and therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Functional imaging of estrogen receptors with radiolabeled-GAP-EDL in rabbit endometriosis model.

PubMed

Takahashi, Nobukazu; Yang, David J; Kurihara, Hiroaki; Borne, Agatha; Kohanim, Saady; Oh, Chang-Sok; Mawlawi, Osama; Kim, E Edmund

2007-09-01

Endometriosis is a common women's health problem. Animal models provide an invaluable tool to study the natural history of endometriosis. We previously have reported that (99m)Tc-labeled glutamate peptide-estradiol ((99m)Tc-GAP-EDL) is a useful agent for imaging functional estrogen receptor (ER) via an ER-mediated process. This study was to evaluate the feasibility of using radiolabeled GAP-EDL to image ER-positive (ER +) endometriosis in nonprimate animal models. 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of (99m)Tc and (68)Ga-GAP-EDL inhibition with cold estrone were conducted in 13,762 rat mammary tumor cells. To create a rabbit model with endometriosis, part of uterine tissue was dissected and grafted in the peritoneal wall. Eight weeks after surgery, scintigraphic images were obtained after intravenous injection of (99m)Tc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5-2.0 hours, and (68)Ga-GAP-EDL at 45 minutes. We also performed (68)Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination. In vitro uptake study of (99m)Tc- and (68)Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of (68)Ga-GAP-EDL in 13,762 cells was inhibited with cold estrone in a dose-dependent manner. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Necropsy was performed at 2.5 hours after injection time. Four follicular endometrial lesions in eight implanted endometrial tissues were detected, and all lesions could be detected by (99m)Tc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of (99m)Tc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that (99m)Tc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, (68)Ga-GAP-EDL accumulation in the endometrial grafts could not be visualized, and endometrial tissue-to-normal tissue count ratios were statistically higher in a nonblocked image than that in the blocked image. Endometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

Tc-99m macro aggregated albumin scintigraphy – indications other than pulmonary embolism: A pictorial essay

PubMed Central

Gandhi, Sunny J; Babu, Sanjay; Subramanyam, Padma; Shanmuga Sundaram, Palaniswamy

2013-01-01

Introduction: Tc-99m macro aggregated albumin (MAA) is synonymous for lung perfusion scintigraphy and is part of the study in the evaluation of pulmonary thromboembolism. We wanted to highlight the utilities of Tc-99m MAA other than pulmonary embolism as a pictorial assay. Materials and Methods: Patients referred for Tc-99m MAA scintigraphy under various indications were included in this pictorial essay. Commercially available TechneScan LyoMAA cold kit from Mallinckrodt Medical B.V., Holland was used. Acquisition protocols for different indications are described in this article. Different clinical indications (e.g., pulmonary artery stenosis, hepatopulmonary syndrome, FEV1 calculation in lung surgery planning, selective internal radiation therapy planning, venography for deep venous thrombosis, left to right cardiac shunts, etc.) where Tc-99m MAA scintigraphy was asked for; how it helped in different clinical scenarios and how it can be used clinically is explained with unique and interesting case examples and images. We also reviewed the literature to look for certain remote indications of MAA imaging for the sake of completion like – (shunt scintigraphy, peritoneopleural communication, etc.) Conclusion: Tc-99m MAA is a very useful radiopharmaceutical, which can be used for many other indications apart from the commonly used indication of lung perfusion scan in pulmonary embolism. It can provide useful clinical information in other indications, which we try to highlight in this article. PMID:24250023

Scatter and cross-talk corrections in simultaneous Tc-99m/I-123 brain SPECT using constrained factor analysis and artificial neural networks

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Maksud, P.; Kijewski, M. F.; Haberi, M. O.; Todd-Pokropek, A.; Aurengo, A.; Moore, S. C.

2000-08-01

Simultaneous imaging of Tc-99m and I-123 would have a high clinical potential in the assessment of brain perfusion (Tc-99m) and neurotransmission (I-123) but is hindered by cross-talk between the two radionuclides. Monte Carlo simulations of 15 different dual-isotope studies were performed using a digital brain phantom. Several physiologic Tc-99m and I-123 uptake patterns were modeled in the brain structures. Two methods were considered to correct for cross-talk from both scattered and unscattered photons: constrained spectral factor analysis (SFA) and artificial neural networks (ANN). The accuracy and precision of reconstructed pixel values within several brain structures were compared to those obtained with an energy windowing method (WSA). In I-123 images, mean bias was close to 10% in all structures for SFA and ANN and between 14% (in the caudate nucleus) and 25% (in the cerebellum) for WSA. Tc-99m activity was overestimated by 35% in the cortex and 53% in the caudate nucleus with WSA, but by less than 9% in all structures with SFA and ANN. SFA and ANN performed well even in the presence of high-energy I-123 photons. The accuracy was greatly improved by incorporating the contamination into the SFA model or in the learning phase for ANN. SFA and ANN are promising approaches to correct for cross-talk in simultaneous Tc-99m/I-123 SPECT.

Radiopharmaceuticals for SPECT cancer detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chernov, V. I., E-mail: chernov@oncology.tomsk.ru; Medvedeva, A. A., E-mail: tickayaAA@oncology.tomsk.ru; Zelchan, R. V., E-mail: r.zelchan@yandex.ru

2016-08-02

The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with {sup 199}Tl and {sup 99}mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal {sup 199}Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of {sup 199}Tlmore » SPECT. In the breast cancer patients, the increased {sup 199}Tl uptake in the breast was visualized in 94.8% patients, {sup 99m}Tc-MIBI—in 93.4% patients. The increased {sup 199}Tl uptake in axillary lymph nodes was detected in 60% patients, and {sup 99m}Tc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI was 95%. The {sup 199}Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the {sup 99m}Tc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI can be used as one of the additional imaging methods in detection of tumors.« less

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours

PubMed Central

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Ömer

2013-01-01

Objective: The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-Octreotate in comparison with 111Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Methods: Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both 99mTc- EDDA/HYNIC-octreotate and 111In-pentetrotide. Images were evaluated both visually and semiquantitatively. Results: On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by 99mTc- EDDA/HYNICOctreotate were higher than the number of lesions detected by 111In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT 99mTc- EDDA/HYNIC-Octreotate scans. Conclusion: The results of this study suggested that, 99mTc- EDDA/HYNIC-Octreotate may be a better alternative to 111In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. Conflict of interest:None declared. PMID:24416622

Radionuclide Basics: Technetium-99

EPA Pesticide Factsheets

Technetium-99 (chemical symbol Tc-99) is a silver-gray, radioactive metal. It occurs naturally in very small amounts in the earth's crust, but is primarily man-made. Technetium-99m is a short-lived form of Tc-99 that is used as a medical diagnostic tool.

Synthesis and evaluation of a (99m)Tc-MAMA-propyl-thymidine complex as a potential probe for in vivo visualization of tumor cell proliferation with SPECT.

PubMed

Celen, Sofie; de Groot, Tjibbe; Balzarini, Jan; Vunckx, Kathleen; Terwinghe, Christelle; Vermaelen, Peter; Van Berckelaer, Lizette; Vanbilloen, Hubert; Nuyts, Johan; Mortelmans, Luc; Verbruggen, Alfons; Bormans, Guy

2007-04-01

Cytosolic thymidine kinase (TK1) catalyzes phosphorylation of thymidine to its monophosphate. TK1 activity is closely related with DNA synthesis, and thymidine analogs derivatized with bulky carboranylalkyl groups at the N-3 position were reported to be good substrates for TK1. Accordingly, we have synthesized (99m)Tc-MAMA-propyl-thymidine and evaluated it as a potential tumor tracer. The bis(S-trityl)-protected MAMA-propyl-thymidine precursor (3-N-[S-trityl-2-mercaptoethyl]-N-[N'-(S-trityl-2-mercaptoethyl)amidoacetyl]-aminopropyl-thymidine) was prepared in three steps, and its structure was confirmed with (1)H NMR and mass spectrometry. Deprotection of the thiols and labeling with (99m)Tc were done in a two-step, one-pot procedure, yielding (99m)Tc-MAMA-propyl-thymidine, which was analyzed with high-performance liquid chromatography, radio-LC-MS analysis (ESI+) and electrophoresis, and its log P was determined. The biodistribution in normal mice was evaluated, and its biodistribution in a radiation-induced fibrosarcoma (RIF) tumor mouse was compared with that of 3'-deoxy-3'-[(18)F] fluorothymidine [(18)F]FLT. (99m)Tc-MAMA-propyl-thymidine was obtained with a radiochemical yield of 70%. Electrophoresis indicated that the complex is uncharged, and its log P was 1.0. The molecular ion mass of the Tc complex was 589 Da, which is compatible with the hypothesized N(2)S(2)-oxotechnetium structure. Tissue distribution showed fast clearance from plasma primarily by the hepatobiliary pathway. Whole-body planar imaging after injection of (99m)Tc-MAMA-propyl-thymidine in an RIF tumor-bearing mouse showed high uptake in the liver and the intestines. No uptake was observed in the tumor, in contrast to the clear uptake observed for [(18)F] FLT visualized with muPET. Although it has been reported that TK1 accepts large substituents at the N-3 position of the thymine ring, the results of this study show that (99m)Tc-MAMA-propyl-thymidine cannot be used as a single photon emission computed tomography tumor tracer, probably because the (99m)Tc-MAMA ligand is too bulky to be tolerated by TK1.

Positioning irrigation of contrast cystography for diagnosis of occult vesicoureteric reflux: association with technetium-99m dimercaptosuccinic acid scans.

PubMed

Berger, Christoph; Becker, Tanja; Koen, Mark; Zeino, Mazen; Fitz, Friedrich; Beheshti, Mohsen; Wolf-Kohlmeier, Iris; Haim, Silke; Riccabona, Marcus

2013-12-01

Positioning irrigation of contrast (PIC) cystography identifies occult or PIC vesicoureteral reflux (PIC-VUR) in children with recurrent febrile urinary tract infections (UTI) but no vesicoureteric reflux (VUR) on standard voiding cystourethrogram (VCUG). We sought to identify the relationship between PIC-VUR and renal scarring in technetium-99m dimercaptosuccinic acid (DMSA) scans. We retrospectively analysed PIC cystograms and DMSA scans for 154 kidneys in 81 children (65 girls; 16 boys; median age, 4.7 years; range, 0.9-15.2). Renal scarring was graded on a scale of 0-3. DMSA scans were pathologic in 66 patients (81%). Children had experienced mean 3.8 febrile UTI (range 1-25). Forty-seven (58%) children had a history of reflux, including 15 (19%) with previous anti-reflux operations. Indications for PIC cystography were recurrence of febrile UTI after either bilateral negative VCUG (66 children) or unilateral VUR (15 children) with contralateral/bilateral scarring or reflux that had changed sides in subsequent VCUGs. PIC-VUR was bilateral in 63, unilateral in 12, and absent in 6 children. Statistically significant associations between PIC-VUR grade and severity of renal scarring were identified in inter-individual (n = 77, p = 0.017) and intra-individual (refluxing vs. nonrefluxing kidney; n = 12, p = 0.008) analyses. After excluding patients with history of VUR, statistical significance was maintained in inter-individual analysis (n = 49; p = 0.018). The data suggest an association between PIC-VUR and severity of renal scarring, and legitimise the use of PIC cystography in children with renal scarring due to recurrent febrile UTI but negative findings on VCUG. Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics.

PubMed

Park-Holohan, S J; Blake, G M; Fogelman, I

2001-09-01

We report a study of the renal and whole-blood kinetics of (18)F-fluoride and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) and their effect on the evaluation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intravenous injection of 18F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and (125)I-human serum albumin ((125)I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. (51)Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. (125)I-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: (99m)Tc-MDP, 58.2% (4.8%); (18)F-fluoride, 36.1% (5.7%); (51)Cr-EDTA, 81.5% (4.5%). Plots of the renal clearance of (18)F-fluoride against urine volume showed that urine flow rates greater than 5 ml.min-1 were necessary to ensure a constant renal clearance of (18)F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of (99m)Tc-MDP. For MDP, the evaluation of skeletal kinetics requires data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ratio of total (99m)Tc-MDP renal clearance to GFR based on the principle that free (99m)Tc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein binding of MDP increased linearly with time, changing from 21+/-5% immediately after injection to 58+/-5% at 4 h. Although red cell uptake of (99m)Tc-MDP was negligible, for (18)F-fluoride around 30% of circulating tracer was transported in red cells. In view of the data showing the rapid transport of (18)F-fluoride across the red cell membrane, bone kinetic data for (18)F are more accurately reported as whole-blood clearance rather than plasma clearance.

The feasibility of imaging myocardial ischemic/reperfusion injury using (99m)Tc-labeled duramycin in a porcine model.

PubMed

Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E; Audi, Said; Zimmer, Michael; Holly, Thomas A; Lee, Daniel C; Zhu, Bao; Zhu, Haibo; Zhao, Ming

2015-02-01

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. (99m)Tc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of (99m)Tc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia-reperfusion injury. The clearance and distribution of intravenously injected (99m)Tc-duramycin were characterized in sham-operated animals (n=5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n=9). (99m)Tc-duramycin (10-15mCi) was injected intravenously at 1hour after reperfusion. SPECT/CT was acquired at 1 and 3hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, (99m)Tc-tetrafosamin scan was performed on the second day to identify the infarct site. Intravenously injected (99m)Tc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6±0.3minutes and β-phase half-life of 179.9±64.7minutes. In control animals, the ratios between normal heart and lung were 1.76±0.21, 1.66±0.22, 1.50±0.20 and 1.75±0.31 at 0.5, 1, 2 and 3hours post-injection, respectively. The ratios between normal heart and liver were 0.88±0.13, 0.80±0.13, 0.82±0.19 and 0.88±0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57±0.74 and 3.69±0.91 at 1 and 3hours post-injection, respectively. Ischemic-to-lung ratios were 4.89±0.85 and 4.93±0.57; and ischemic-to-liver ratios were 2.05±0.30 to 3.23±0.78. The size of (99m)Tc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in (99m)Tc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography. (99m)Tc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion. Copyright © 2014 Elsevier Inc. All rights reserved.

The feasibility of imaging myocardial ischemic/reperfusion injury using 99mTc-labeled duramycin in a porcine model

PubMed Central

Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E.; Audi, Said; Zimmer, Michael; Holly, Thomas A; Lee, Daniel; Zhu, Bao; Zhu, Haibo; Zhao, Ming

2015-01-01

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia-reperfusion injury. Methods The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10-15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting was used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Results Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0.78. The size of 99mTc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in 99mTc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography. Conclusion 99mTc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion. PMID:25451214

Dynamic CT for Parathyroid Adenoma Detection: How Does Radiation Dose Compare With Nuclear Medicine?

PubMed

Czarnecki, Caroline A; Einsiedel, Paul F; Phal, Pramit M; Miller, Julie A; Lichtenstein, Meir; Stella, Damien L

2018-05-01

Dynamic CT is increasingly used for preoperative localization of parathyroid adenomas, but concerns remain about the radiation effective dose of CT compared with that of 99m Tc-sestamibi scintigraphy. The purpose of this study was to compare the radiation dose delivered by three-phase dynamic CT with that delivered by 99m Tc-sestamibi SPECT/CT performed in accordance with our current protocols and to assess the possible reduction in effective dose achieved by decreasing the scan length (i.e., z-axis) of two phases of the dynamic CT protocol. The effective dose of a 99m Tc-sestamibi nuclear medicine parathyroid study performed with and without coregistration CT was calculated and compared with the effective dose of our current three-phase dynamic CT protocol as well as a proposed protocol involving CT with reduced scan length. The median effective dose for a 99m Tc-sestamibi nuclear medicine study was 5.6 mSv. This increased to 12.4 mSv with the addition of coregistration CT, which is higher than the median effective dose of 9.3 mSv associated with the dynamic CT protocol. Reducing the scan length of two phases in the dynamic CT protocol could reduce the median effective dose to 6.1 mSv, which would be similar to that of the dose from the 99m Tc-sestamibi study alone. Dynamic CT used for the detection of parathyroid adenoma can deliver a lower radiation dose than 99m Tc-sestamibi SPECT/CT. It may be possible to reduce the dose further by decreasing the scan length of two of the phases, although whether this has an impact on accuracy of the localization needs further investigation.

Regional brain hematocrit in stroke by single photon emission computed tomography imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loutfi, I.; Frackowiak, R.S.; Myers, M.J.

1987-01-01

Nineteen studies on 18 subjects were performed by single photon emission computed tomography (SPECT) of the head after the successive intravenous administration of a plasma label (/sup 99m/Tc-human serum albumin (HSA)) and /sup 99m/Tc-labeled autologous red blood cells (RBC). Two sets of cerebral tomographic sections were generated: for cerebral /sup 99m/Tc-HSA alone and for combined /sup 99m/Tc-HSA and /sup 99m/Tc-RBC. By relating counts in regions of interest from the cerebral tomograms to counts from blood samples obtained during each tomographic acquisition, regional cerebral haematocrit (Hct) was calculated by the application of a simple formula. Results show 1) lower cerebral Hctmore » than venous Hct (ratio of HCT brain/Hct venous 0.65-0.90) in all subjects, and 2) comparison between right and left hemisphere Hct in 3/3 normal subjects, 6/6 patients with transient ischaemic attacks and 3/8 patients with stroke showed no significant difference. However, in 3/8 patients with stroke (most recent strokes) significant differences were found, the higher Hct value corresponding to the affected side.« less

(99m)Tc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of NET: a case of metastatic duodenal carcinoid.

PubMed

Hubalewska-Dydejczyk, Alicja; Szybiński, Piotr; Fröss-Baron, Katarzyna; Mikolajczak, Renata; Huszno, Bohdan; Sowa-Staszczak, Anna

2005-01-01

Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for the diagnostics of neuroendocrine tumours (NET). (99m)Tc-EDDA/HYNIC-octreotate (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar physiological biodistribution to (111)In-Octreoscan. We present a case of a 47-year-old man with disseminated duodenal carcinoid. The patient had been operated due to the tumour mass detected in pancreatic head area. Histopathology revealed carcinoid of the duodenal wall with local lymph node and liver metastases. The patient was qualified for chemotherapy stopped due to severe leucopenia. (99m)Tc EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple metastatic lesions were detected all over the body. The high quality images with high target/non target ratio were obtained. (99m)Tc-MDP scintigraphy confirmed multiple bone metastases. On the basis of SRS result the patient was qualified for 90Y-DOTA-TATE therapy. In conclusion, (99m)Tc EDDA/HYNIC-octreotate can be regarded as a promising tracer for staging and to determine SSTR status of NET.

Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinkle, G.H.; Basmadjian, G.P.; Peek, C.

Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated withmore » other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate.« less

The use of {sup 99m}Tc-Al{sub 2}O{sub 3} for detection of sentinel lymph nodes in breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinilkin, I., E-mail: sinilkinig@oncology.tomsk.ru; Chernov, V.; Medvedeva, A.

2016-08-02

Purpose: to study the feasibility of using the new radiopharmaceutical based on the technetium-99m-labeled gamma-alumina for identification of sentinel lymph nodes (SLNs) in breast cancer patients. The study included two groups of breast cancer patients who underwent single photon emission computed tomography (SPECT) and intraoperaive gamma probe identification of sentinel lymph nodes (SLNs). To identify SLNs, the day before surgery Group I patients (n = 34) were injected with radioactive {sup 99m}Tc-Al{sub 2}O{sub 3}, and Group II patients (n = 30) received {sup 99m}Tc-labeled phytate colloid. A total of 37 SLNs were detected in Group I patients. The number ofmore » identified SLNs per patient ranged from 1 to 2 (the average number of identified SLNs was 1.08). Axillary lymph nodes were the most common site of SLN localization. 18 hours after {sup 99m}Tc-Al{sub 2}O{sub 3} injection, the percentage of its accumulation in the SLN was 7–11% (of the counts in the injection site) by SPECT and 17–31% by gamma probe detection. In Group II SLNs were detected in 27 patients. 18 hours after injection of the phytate colloid the percentage of its accumulation in the SLN was 1.5–2% out of the counts in the injection site by SPECT and 4–7% by gamma probe. The new radiopharmaceutical based on the {sup 99m}Tc-Al{sub 2}O{sub 3} demonstrates high accumulation in SLNs without redistribution through the entire lymphatic basin. The sensitivity and specificity of {sup 99m}Tc-Al{sub 2}O{sub 3} were 100% for both SPECT and intraoperative gamma probe identification.« less

Early myocardial damage assessment in dystrophinopathies using (99)Tc(m)-MIBI gated myocardial perfusion imaging.

PubMed

Zhang, Li; Liu, Zhe; Hu, Ke-You; Tian, Qing-Bao; Wei, Ling-Ge; Zhao, Zhe; Shen, Hong-Rui; Hu, Jing

2015-01-01

Early detection of muscular dystrophy (MD)-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m-methoxyisobutylisonitrile ((99)Tc(m)-MIBI) gated myocardial perfusion imaging (G-MPI) for MD. Ninety-one patients underwent (99)Tc(m)-MIBI G-MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD) (n=77) or Becker muscular dystrophy (BMD; n=14). (99)Tc(m)-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using (99)Tc(m)-MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (r s=0.534 [P<0.05] and r s=0.784 [P<0.05], respectively). Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05), but not in BMD patients. (99)Tc(m)-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD, and can serve as a candidate method for the evaluation of progression, prognosis, and assessment of the effect of glucocorticoid treatment in these patients.

Periarticular uptake of /sup 99m/technetium diphosphonate in psoriatics. Correlation with cutaneous activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Namey, T.C.; Rosenthall, L.

1976-01-01

The periarticular uptake of /sup 99m/technetium-labeled diphosphonate (/sup 99m/TcDP) was compared in 12 patients hospitalized for psoriasis and in 12 hospitalized for other dermatoses not associated with arthropathy. The 12 patients with psoriasis had recent onset disease of less than 5 years duration; neither group had historical or clinical evidence of arthritis. All psoriatics had markedly abnormal scans with symmetrically increased periarticular uptake about the imaged joints. None of the controls had similar findings. In 4 patients scanned with /sup 99m/technetium-pertechnetate within 24 hours of their /sup 99m/TcDP scan, no evidence of inflammatory synovitis was found. Three of these patientsmore » were serially imaged with /sup 99m/TcDP at intervals of 2 weeks to 3 months after their initial study, when obvious clinical improvement in their psoriasis was apparent. Improvement in the radionuclide joint images was demonstrated in some of the patients, but none reverted to normal during the study period. In light of recent evidence for the preferential binding of /sup 99m/TcDP to immature collagen, it is suggested that psoriasis may represent a generalized, but uncharacterized, collagen disorder present in bone as well as skin, linking the cutaneous disease with the potential for arthropathy.« less

Rapid diagnosis of occult abscesses using sup 99m Tc-labeled monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coons, T.A.; Rhodes, B.A.; Thakur, M.L.

1991-01-01

Acute infections, such as appendicitis and occult infections in AIDS patients, can be diagnosed within two hours by gamma scintigraphy after i.v. administration of {sup 99m}Tc labeled antibodies reactive with human granulocytes. The antibody, murine IgM anti-SSEA-1, is partially reduced using Sn(II) to expose and protect reactive sulfide groups. The antibody is then purified, stannous tartrate and stabilizers are added, and the mixture is lyophilized. To label, sodium pertechnetate is added. After a 15 minute incubation the tracer drug is injected. The rate of accumulation and degree of concentration at the site of infection is presumptively determinative of the severitymore » of the infection. Acceptance criteria and tests for the {sup 99m}Tc labeled antibody product have been established and validated. Greater than 93% of the {sup 99m}Tc is firmly bound to the protein as determined by quantitative HPLC. Radiochemical impurities, colloidal {sup 99m}Tc and free pertechnetate are together less than 4% as determined by thin layer chromatography. The immunoreactive fraction, measured by binding to solid phase antigen, and affinity measured be ELISA, are unchanged by the {sup 99m}Tc-direct labeling process. Two hour blood clearance in rats is within 90% of the value of the {sup 125}I labeled analog. The immunoreactive fraction decreases less than 10% when incubated in human plasma for 24 hours. This method has been compared to other direct labeling methods, and found to give higher radiochemical yields. 5 figs.« less

Diagnostic role of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases.

PubMed

Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

2014-01-01

The bone metastasis appeared early before the bone imaging for most of the above patients. (99)Tc(m)-MDP ((99)Tc(m) marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi (99)Tc(m)-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, (99)Tc(m)-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.

PubMed

Sun, Wenjing; Chu, Taiwei

2015-10-15

The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification.

PubMed

de Barros, André Luís Branco; Mota, Luciene das Graças; Soares, Daniel Crístian Ferreira; Coelho, Marina Melo Antunes; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2011-12-15

Long-circulating and pH-sensitive liposomes trapping (99m)Tc-HYNIC-βAla-bombesin((7-14)) (aSpHL-(99m)Tc-BBN((7-14))) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor-bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL-(99m)Tc-BBN((7-14)) could be considered as a potential agent for tumor diagnosis. Published by Elsevier Ltd.

Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model.

PubMed

Baldoni, Daniela; Waibel, Robert; Bläuenstein, Peter; Galli, Filippo; Iodice, Violetta; Signore, Alberto; Schibli, Roger; Trampuz, Andrej

2015-12-01

Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Maximum binding (mean ± SD) of [(57)Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [(99m)Tc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [(57)Co]Cbl for E. coli and S. aureus, respectively. In vivo, [(99m)Tc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [(99m)Tc]DTPA, which showed similar biodistribution in infected and sterile mice. [(57)Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [(67)Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P < 0.05). Cbl displayed rapid and specific in vitro binding to test strains. [(99m)Tc]PAMA(4)-Cbl was rapidly cleared from most tissues and discriminated between sterile and infected cages, being a promising candidate for imaging infections in humans.

Estimation of internal exposure to 99Mo in nuclear medicine patients.

PubMed

Silva, I C O A; Lucena, E A; Souza, W O; Dantas, A L A; Dantas, B M

2010-05-10

(99m)Tc is the most widely used radionuclide in nuclear medicine. It is obtained by elution of (99)Mo-(99m)Tc generators. Depending on the quality of the generator and its integrity, (99)Mo may be extracted from the column during the elution process, becoming a radionuclidic impurity in the (99m)Tc eluate. This fact would impart an unnecessary dose to the patients submitted to diagnostic procedures. The aim of this work is to evaluate (99)Mo incorporation and internal effective doses in nuclear medicine patients through bioassay techniques, providing information on the metabolism of molybdenum in humans. A methodology based on in vivo and in vitro measurements was developed. In vivo measurements were performed with a NaI detector installed in the IRD WBC. Urine samples were analysed with a HPGe at the IRD bioassay laboratory. Patients showed detectable activities of (99)Mo in whole body and urine. Results were interpreted with AIDE software. Estimated incorporation was compared to predicted values based on ICRP model. Effective doses were in the order of micro sieverts. Results suggest the need to implement a routine quality control program of radionuclidic impurity of (99)Mo in (99m)Tc eluates to be conducted by radiopharmacy laboratories of nuclear medicine centers.

Micro-SPECT/CT-based pharmacokinetic analysis of 99mTc-diethylenetriaminepentaacetic acid in rats with blood-brain barrier disruption induced by focused ultrasound.

PubMed

Yang, Feng-Yi; Wang, Hsin-Ell; Lin, Guan-Liang; Teng, Ming-Che; Lin, Hui-Hsien; Wong, Tai-Tong; Liu, Ren-Shyan

2011-03-01

This study evaluated the pharmacokinetics of (99m)Tc-diethylenetriamine pentaacetate acid ((99m)Tc-DTPA) after intravenous administration in healthy and F98 glioma-bearing F344 rats in the presence of blood-brain barrier disruption (BBB-D) induced by focused ultrasound (FUS). The pharmacokinetics of the healthy and tumor-containing brains after BBB-D were compared to identify the optimal time period for combined treatment. Healthy and F98 glioma-bearing rats were injected intravenously with Evans blue (EB) and (99m)Tc-DTPA; these treatments took place with or without BBB-D induced by transcranial FUS of 1 hemisphere of the brain. The permeability of the BBB was quantified by EB extravasation. Twelve rats were scanned for 2 h to estimate uptake of (99m)Tc radioactivity with respect to time for the pharmacokinetic analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to examine tissue damage. The accumulations of EB and (99m)Tc-DTPA in normal brains or brains with a tumor were significantly elevated after the intravenous injection when BBB-D was induced. The disruption-to-nondisruption ratio of the brains and the tumor-to-ipsilateral brain ratio of the tumors in terms of radioactivity reached a peak at 45 and 60 min, respectively. EB injection followed by sonication showed that there was an increase of about 2-fold in the tumor-to-ipsilateral brain EB ratio of the target tumors (7.36), compared with the control tumors (3.73). TUNEL staining showed no significant differences between the sonicated tumors and control tumors. This study demonstrates that (99m)Tc-DTPA micro-SPECT/CT can be used for the pharmacokinetic analysis of BBB-D induced by FUS. This method should be able to provide important information that will help with establishing an optimal treatment protocol for drug administration after FUS-induced BBB-D in clinical brain disease therapy.

Nuclear medicine in breast cancer diagnostics: Primary tumor and lymphatic metastasis

NASA Astrophysics Data System (ADS)

Sinilkin, I.; Medvedeva, A.; Chernov, V.; Slonimskaya, E.; Zelchan, R.; Bragina, O.

2017-09-01

The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer.

Improved Quantification of the Beta Cell Mass after Pancreas Visualization with 99mTc-demobesin-4 and Beta Cell Imaging with 111In-exendin-3 in Rodents.

PubMed

van der Kroon, Inge; Joosten, Lieke; Nock, Berthold A; Maina, Theodosia; Boerman, Otto C; Brom, Maarten; Gotthardt, Martin

2016-10-03

Accurate assessment of the 111 In-exendin-3 uptake within the pancreas requires exact delineation of the pancreas, which is highly challenging by MRI and CT in rodents. In this study, the pancreatic tracer 99m Tc-demobesin-4 was evaluated for accurate delineation of the pancreas to be able to accurately quantify 111 In-exendin-3 uptake within the pancreas. Healthy and alloxan-induced diabetic Brown Norway rats were injected with the pancreatic tracer 99m Tc-demobesin-4 ([ 99m Tc-N 4 -Pro 1 ,Tyr 4 ,Nle 14 ]bombesin) and the beta cell tracer 111 In-exendin-3 ([ 111 In-DTPA-Lys 40 ]exendin-3). After dual isotope acquisition of SPECT images, 99m Tc-demobesin-4 was used to define a volume of interest for the pancreas in SPECT images subsequently the 111 In-exendin-3 uptake within this region was quantified. Furthermore, biodistribution and autoradiography were performed in order to gain insight in the distribution of both tracers in the animals. 99m Tc-demobesin-4 showed high accumulation in the pancreas. The uptake was highly homogeneous throughout the pancreas, independent of diabetic status, as demonstrated by autoradiography, whereas 111 In-exendin-3 only accumulates in the islets of Langerhans. Quantification of both ex vivo and in vivo SPECT images resulted in an excellent linear correlation between the pancreatic uptake, determined with ex vivo counting and 111 In-exendin-3 uptake, determined from the quantitative analysis of the SPECT images (Pearson r = 0.97, Pearson r = 0.92). 99m Tc-demobesin-4 shows high accumulation in the pancreas of rats. It is a suitable tracer for accurate delineation of the pancreas and can be conveniently used for simultaneous acquisition with 111 In labeled exendin-3. This method provides a straightforward, reliable, and objective method for preclinical beta cell mass (BCM) quantification with 111 In-exendin-3.

Computed tomography hepatic arteriography has a hepatic falciform artery detection rate that is much higher than that of digital subtraction angiography and 99mTc-MAA SPECT/CT: implications for planning 90Y radioembolization?

PubMed

Burgmans, M C; Too, C W; Kao, Y H; Goh, A S W; Chow, P K H; Tan, B S; Tay, K H; Lo, R H G

2012-12-01

To compare the hepatic falciform artery (HFA) detection rates of digital subtraction angiography (DSA), computed tomography hepatic arteriography (CTHA) and 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed tomography with integrated CT (SPECT/CT) and to correlate HFA patency with complication rates of yttrium-90 (90Y) radioembolization. From August 2008 to November 2010, 79 patients (range 23-83 years, mean 62.3 years; 67 male) underwent pre-treatment DSA, CTHA and 99mTc-MAA scintigraphy (planar/SPECT/CT) to assess suitability for radioembolization with 90Y resin microspheres. Thirty-seven patients were excluded from the study, because CTHA was performed with a catheter position that did not result in opacification of the liver parenchyma adjacent to the falciform ligament. DSA, CTHA and 99mTc-MAA SPECT/CT images and medical records were retrospectively reviewed. A patent HFA was detected in 22 of 42 patients (52.3%). The HFA detection rates of DSA, CTHA and 99mTc-MAA SPECT/CT were 11.9%, 52.3% and 13.3%, respectively (p<0.0001). An origin from the segment 4 artery was seen in 51.7% of HFAs. Prophylactic HFA coil-embolization prior to 90Y microspheres infusion was performed in 2 patients. Of the patients who underwent radioembolization with a patent HFA, none developed supra-umbilical radiation dermatitis. One patient experienced epigastric pain attributed to post-embolization syndrome and was managed conservatively. The HFA detection rate of CTHA is superior to that of DSA and 99mTc-MAA SPECT/CT. Complications related to non-target radiation of the HFA vascular territory rarely occur, even in patients undergoing radioembolization with a patent HFA. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[99mTc-octreotide receptor scintigraphy in NCI-H446 small cell lung cancer nude mice model].

PubMed

Li, Chao; Zuo, Shuyao; Wang, Xufu; Liu, Xinfeng; Wang, Guoming; Wu, Fengyu

2015-01-01

For highly aggressive small cell lung cancer (SCLC), early diagnosis is important for its prognosis, but the current inspection methods are more limited, with poor specificity of the traditional imaging methods, and the high cost of PET/CT, difficult to popularization and application. SCLC is kind of neuroendocrine tumors, high expression of somatostatin receptors, which is the cornerstone of its early molecular imaging diagnosis. The aim of this study is to observe the biodistribution and metabolism of 99mTc-octreotide in normal and the human SCLC bearing nude mice. Dynamic and static scintigraphy at 0.5 h, 2 h, 3 h, 4 h were performed in both normal and tumor bearing nude mice after intravenous injection of 99mTc-octreotide. The technique of drawing region of interest (ROI) was used to obtain the averaged pixel counts and the activity-time (A-T) curve of brain, heart, lung, liver, kidney, tumor, respectively. ① The biodistribution study in normal nude mice showed highest uptake in kidney and liver, lower in lung and heart, lowest in brain. Most 99mTc-octreotide was excreted via kidney. ② All tumors were displayed clearly at 3 h postinjection of 99mTc-octreotide. The averaged T/N ratio at 0.5 h, 2 h, 3 h, 4 h postinjection of 99mTc-octreotide was 1.163 ± 0.03, 2.08 ± 0.12, 3.03 ± 0.23, 2.689 ± 0.31, respectively (F=51.69, P<0.000,1). The radioactivity of tumor was lower than liver, and similar with the lung. The curve of tumor showed a radioactivity peak at 2 min-3 min postinjection. 99mTc-octreotide receptor imaging on nude mice bearing SCLC shares high positive rate, especially at 3 h postinjection.

99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours.

PubMed

von Guggenberg, E; Dietrich, H; Skvortsova, I; Gabriel, M; Virgolini, I J; Decristoforo, C

2007-08-01

Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA(0),D: Glu(1)]minigastrin (DTPA-MG0) radiolabelled with (111)In and (90)Y, our group developed a (99m)Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC(0),D: Glu(1),desGlu(2-6)]minigastrin (HYNIC-MG11). (99m)Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. (99m)Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of (99m)Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. (99m)Tc-EDDA-HYNIC-MG11 shows advantages over (99m)Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement.

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours; first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives.

PubMed

Decristoforo, C; Mather, S J; Cholewinski, W; Donnemiller, E; Riccabona, G; Moncayo, R

2000-09-01

[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

PubMed

Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

2014-10-01

The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

(99m)Tc-labeled SWL specific peptide for targeting EphA2 receptor.

PubMed

Liu, Yu; Lan, Xiaoli; Wu, Tao; Lang, Juntao; Jin, Xueyan; Sun, Xun; Wen, Qiong; An, Rui

2014-07-01

EphA2, one member of the Eph receptor family, is widely expressed in multiple aggressive cancers. SWL, a small peptide identified by phage display, has high binding affinity to EphA2, suggesting that it could be exploited for targeted molecular imaging. Therefore, a novel peptide-based probe, (99m)Tc-HYNIC-SWL, was developed and its potential to specifically target EphA2-positive tumors was investigated. The SWL peptide was labeled with hydrazinonicotinic acid (HYNIC), followed by (99m)Tc labeling. Immunofluorescence staining was carried out to detect the expression of EphA2 in A549 lung cancer cells and OCM-1 melanoma cells. Saturation binding experiments were performed by incubating A549 cells with increasing concentrations of radiolabeled peptide in vitro. To test the probe in vivo, nude mice bearing either A549 or OCM-1 derived tumors were established, injected with (99m)Tc-HYNIC-SWL, and subjected to SPECT imaging. Mice injected with excess unlabeled SWL were used as a specific control. Ex vivo γ-counting of dissected tissues from the mice was also performed to evaluate biodistribution. Immunofluorescence staining showed that A549 cells intensively expressed EphA2, while OCM-1 cells had little expression. (99m)Tc-HYNIC-SWL displayed high binding affinity with A549 cells (KD=2.6±0.7nM). From the SPECT images and the results of the biodistribution study, significantly higher uptake of the tracer was seen in A549 tumors (1.44±0.12 %ID/g) than in OCM-1 tumors (0.43±0.20 %ID/g) at 1h after injection. Pre-injection with excess unlabeled peptide in A549-bearing nude mice, significantly reduced tumor uptake of the radiolabeled probe (0.58±0.20 %ID/g) was seen. These data suggest that (99m)Tc-HYNIC-SWL specifically targets EphA2 in tumors. The expression of EphA2 can be noninvasively investigated using (99m)Tc-HYNIC-SWL by SPECT imaging. The in vitro and in vivo characteristics of (99m)Tc-HYNIC-SWL make it a promising probe for EphA2-positive tumor imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

MO-F-CAMPUS-I-05: Radiation Dosimetry of 99mTc-IDA-D-[c(RGDfK)]2, a SPECT Agent for Angiogenesis Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J

2015-06-15

Purpose: Tc-99m labeled IDA-D-[c(RGDfK){sub 2} ( {sup 99m}Tc-RGD) is a recently developed radiotracer for gamma camera or single photon emission computed tomography (SPECT) imaging and promising agent for the visualization of angiogenesis. In this study, we investigated the internal radiation dosimetry of {sup 99m}Tc-RGD in humans. Methods: Six normal controls (F:M=4:2; 68.3±3.2 years; 56.5±10.7 kg) were participated in this study. Simultaneous anterior and posterior scans of whole-body were performed using dual head gamma camera system. Before the emission scan, transmission scan was performed just before injection of {sup 99m}Tc-RGD using Co-57 flood source. After an intravenous injection of 388.7±29.3 MBqmore » of {sup 99m}Tc-RGD, six serial emission scans were performed at 0, 1, 2, 4, 8 and 24 hours post-injection. The anterior and posterior images were geometrically averaged and attenuation correction was applied using transmission scan image. Regions of interest (ROIs) were drawn on liver, gallbladder, kidneys, urinary bladder, spleen, brain, and large intestine. Time activity curves were obtained from serial emission scan and ROIs. The number of disintegrations per unit activity administered (residence time) were calculated from the area under the curve of time activity curves and injected dose of each patient. Finally, the radiation dose for each organ and effective doses were obtained using OLINDA/EXM 1.1 software and residence time. Results: High radiation doses were reported on renal and biliary excretion tracks such as urinary bladder wall, upper large intestine, kidneys, liver and gallbladder wall and their doses were 19.15±6.84, 19.28±4.78, 15.67±0.90, 9.13±1.71 and 9.09±2.03 µGy/MBq, respectively. The effective dose and effective dose equivalent were 5.08±0.53 and 7.11±0.58 µSv/MBq, respectively. Conclusion: We evaluated the radiation dose of 99mTc-RGD, which has an acceptable effective radiation dose compare to the other Tc-99m labeled radio-tracers.« less

Clinical translation of a PSMA inhibitor for 99mTc-based SPECT.

PubMed

Ferro-Flores, Guillermina; Luna-Gutiérrez, Myrna; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Orocio-Rodríguez, Emmanuel; Davanzo, Jenny; García-Pérez, Francisco O

2017-05-01

Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68 Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99m Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ( 99m Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99m Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer. 99m Tc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68 Ga-PSMA-617scan) were acquired at 1h and 3h after 99m Tc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%. In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99m Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68 Ga-PSMA-617 does. The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99m Tc-EDDA/HYNIC-iPSMA. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical modeling of yields for proton-induced reactions on natural and enriched molybdenum targets.

PubMed

Celler, A; Hou, X; Bénard, F; Ruth, T

2011-09-07

Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated, as these may affect the diagnostic outcome and radiation dosimetry in human studies. Reaction conditions (beam and target characteristics, and irradiation and cooling times) need to be optimized in order to maximize the amount of (99m)Tc and minimize impurities. Although ultimately careful experimental verification of these conditions must be performed, theoretical calculations can provide the initial guidance allowing for extensive investigations at little cost. We report the results of theoretically determined reaction yields for (99m)Tc and other radioactive isotopes created when natural and enriched molybdenum targets are irradiated by protons. The cross-section calculations were performed using a computer program EMPIRE for the proton energy range 6-30 MeV. A computer graphical user interface for automatic calculation of production yields taking into account various reaction channels leading to the same final product has been created. The proposed approach allows us to theoretically estimate the amount of (99m)Tc and its ratio relative to (99g)Tc and other radioisotopes which must be considered reaction contaminants, potentially contributing to additional patient dose in diagnostic studies.

Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

1981-04-01

Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

The utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors.

PubMed

Pavlovic, S; Artiko, V; Sobic-Saranovic, D; Damjanovic, S; Popovic, B; Jakovic, R; Petrasinovic, Z; Jaksic, E; Todorovic-Tirnanic, M; Saranovic, D; Micev, M; Novosel, S; Nikolic, N; Obradovic, V

2010-01-01

Our aim was to assess clinical utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99mTc-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). T/NT ratios were significantly higher on SPECT than whole body images (2.96+/-1.07 vs.1.70+/-0.43, p 99mTc-EDDA/Hynic-TOC, lung involvement of NETs, T/NT ratio.

A freeze-dried kit formulation for the preparation of Lys(27)(99mTc-EDDA/HYNIC)-Exendin(9-39)/99mTc-EDDA/HYNIC-Tyr3-Octreotide to detect benign and malignant insulinomas.

PubMed

Medina-García, Veronica; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; Santos-Cuevas, Clara L; Aranda-Lara, Liliana; García-Becerra, Rocio; Ordaz-Rosado, David; Melendez-Alafort, Laura

2015-12-01

About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC)-Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97±1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

Significance of technetium-99m human serum albumin diethylenetriamine pentaacetic acid scintigraphy in patients with nephrotic syndrome.

PubMed

Takashima, Tsuyoshi; Kishi, Tomoya; Onozawa, Koji; Rikitake, Shuichi; Miyazono, Motoaki; Otsuka, Takateru; Irie, Hiroyuki; Iwakiri, Ryuichi; Fujimoto, Kazuma; Ikeda, Yuji

2015-01-01

It is thought that a large amount of albumin leaking from the glomerulus in nephrotic syndrome (NS) is reabsorbed at the proximal tubule and catabolized. Therefore, it is possible the final quantity of urinary protein does not always reflect the amount of leakage of protein from the glomerulus. We experienced two cases without nephrotic range proteinuria thought to involve hypoproteinemia due to the same pathophysiology as NS. On these patients, we performed protein leakage scintigraphy with technetium-99m human serum albumin diethylenetriamine pentaacetic acid (99mTc-HSAD) to exclude a diagnosis of protein-losing gastroenteropathy and observed diffuse positive accumulation in the kidneys with more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration. In healthy adults intravenously given 99mTc-HSAD, the same dynamics are observed as in albumin metabolism, and the organ radioactivity of the liver and kidneys after 24 hours is equal. Therefore, we thought it was possible that the renal uptake 24 hours after 99mTc-HSAD administration was a characteristic finding of NS. In order to confirm it, the subjects were divided into two groups: the NS group (n = 10) and the non-NS group (n = 7). We defined more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration as Dense Kidney (+). Furthermore, we designed regions of interest in the right and left kidneys and liver on anterior and posterior images, then calculated the kidney-liver ratio. Nine of the ten patients had Dense Kidney (+) in the NS group, compared to none in the non-NS group. And the kidney-liver ratio was significantly higher in the NS group than in the non-NS group on each view in the bilateral kidneys. In conclusion, our results suggest that the renal uptake 24 hours after 99mTc-HSAD administration is a characteristic finding of NS.

Diagnostic sensitivity of Tc-99m HYNIC PSMA SPECT/CT in prostate carcinoma: A comparative analysis with Ga-68 PSMA PET/CT.

PubMed

Lawal, Ismaheel O; Ankrah, Alfred O; Mokgoro, Neo P; Vorster, Mariza; Maes, Alex; Sathekge, Mike M

2017-08-01

Emerging data from published studies are demonstrating the superiority of Ga-68 PSMA PET/CT imaging in prostate cancer. However, the low yield of the Ge-68/Ga-68 from which Gallium-68 is obtained and fewer installed PET/CT systems compared to the SPECT imaging systems may limit its availability. We, therefore, evaluated in a head-to-head comparison, the diagnostic sensitivity of Ga-68 PSMA PET/CT and Tc-99m PSMA SPECT/CT in patients with prostate cancer. A total of 14 patients with histologically confirmed prostate cancer were prospectively recruited to undergo Ga-68 PSMA PET/CT and Tc-99m HYNIC PSMA SPECT/CT. The mean age of patients was 67.21 ± 8.15 years and the median PSA level was 45.18 ng/mL (range = 1.51-687 ng/mL). SUVmax of all lesions and the size of lymph nodes with PSMA avidity on Ga-68 PSMA PET/CT were determined. Proportions of these lesions detected on Tc-99m HYNIC PSMA SPECT/CT read independent of PET/CT findings were determined. A total of 46 lesions were seen on Ga-68 PSMA PET/CT localized to the prostate (n = 10), lymph nodes (n = 24), and bones (n = 12). Of these, Tc-99m HYNIC PSMA SPECT/CT detected 36 lesions: Prostate = 10/10 (100%), lymph nodes = 15/24 (62.5%), and bones = 11/12 (91.7%) with an overall sensitivity of 78.3%. Lesions detected on Tc-99m HYNIC PSMA SPECT/CT were bigger in size (P < 0.001) and had higher SUVmax (P < 0.001) as measured on Ga-68 PSMA PET/CT compared to those lesions that were not detected. All lymph nodes greater than 10 mm in size were detected while only 28% of nodes less than 10 mm were detected by Tc-99m HYNIC PSMA SPECT/CT. In a univariate analysis, Lymph node size (P = 0.033) and the SUVmax of all lesions (P = 0.007) were significant predictors of lesion detection on Tc-99m HYNIC PSMA SPECT/CT. Tc-99m HYNIC PSMA may be a useful in imaging of prostate cancer although with a lower sensitivity for lesion detection compared to Ga-68 PSMA PET/CT. Its use is recommended when Ga-68 PSMA is not readily available, in planning radio-guided surgery or the patient is being considered for radio-ligand therapy with Lu-177 PSMA. It performs poorly in detecting small-sized lesions hence its use is not recommended in patients with small volume disease. © 2017 Wiley Periodicals, Inc.

Effect of ketamine, pentobarbital, and morphine on Tc-99m-DISIDA hepatobiliary kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Durakovic, A.; Dubois, A.

1985-05-01

The purpose of this study was to evaluate hapatobiliary kinetics of Tc-99m-DISIDA in dogs after administration of anesthetic sedative or narcotic agents. Four groups of six male Beagle dogs were studied as a non-treated control group and after parenteral administration of ketamine (30 mg/kg IM), pentobarbital (25 mg/kg IV) or morphine (1 mg/kg IV). Each animal was injected with 4 mCi Tc-99m-DISIDA and hepatobiliary scintigraphic studies were obtained using a gamma camera with parallel hole multipurpose collimator and an A/sup 3/ MDS computer. The authors determined; peak activity of Tc-99m-DISIDA in the liver, visualization and peak activity of gallbladder, andmore » intestinal visualization of Tc-99m-DISIDA. Total bilirubin, LDH, SGOT and SGPT were not modified significantly after any drug compared to control. The results showed that two commonly used anesthetics and sedatives (ketamine and pentobarbital) have dramatic and opposite effects on extrahepatic biliary kinetics. Furthermore, ketamine, but not pentobarbital, significantly accelerates intrahepatic biliary kinetics. Finally, as expected, morphine delayed extrahepatic biliary kinetics. Thus, studies of biliary kinetics should be interpreted with caution when measurements are made after administration of anesthetic, sedative or narcotic agents.« less

Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to background ratio, on MAA stability and reuse after its first preparation.

PubMed

Malhotra, Anshoo; Kumar, Pardeep; Sharma, Sarika; Dhawan, Davinder K

2010-01-01

The present study was designed to develop stable and economically competitive radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled with (99m)Tc pertechnetate by following the standard protocol which included incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every experiment. The rats were injected intravenously with (99m)Tc MAA and were sacrificed after 10 min to study its distribution in the lungs and other non target tissues using gamma ray spectrometer. This standard protocol was further experimented upon in order to achieve high target to non target ratio. Different formulations were prepared by incubating them at 80 degrees for different incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest target to non target ratio. Another group of rats that received the above formulation were sacrificed after two additional time intervals of 5 and 15 min. The target to non target ratio was high in animals sacrificed after 5 min of injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for different time durations 1, 2 and 9 days were also evaluated for their ability to be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept for 9 days showed the best target to non-target ratio. The present study suggests that MAA once prepared can be reused following labeling with (99m)Tc even after 9 days of storage with better target to non target ratio as compared to storage timer period of 1 and 2 days.

99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

PubMed

Santos-Cuevas, Clara; Davanzo, Jenny; Ferro-Flores, Guillermina; García-Pérez, Francisco O; Ocampo-García, Blanca; Ignacio-Alvarez, Eleazar; Gómez-Argumosa, Edgar; Pedraza-López, Martha

2017-09-01

The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of 99m Tc-EDDA/HYNIC-iPSMA ( 99m Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients. 99m Tc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after 99m Tc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the 99m Tc-EDDA/HYNIC-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h. The blood activity showed a half-life value of 4.98min for the fast component (T 1/2 α=ln2/8.34), 2.49h for the first slow component (T 1/2 β=ln2/0.278), and 9.24h for the second slow component (T 1/2 γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv. All the absorbed doses were comparable to those known for most of the 99m Tc studies. 99m Tc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical to target site-specific prostate cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Labeling and Biological Evaluation of (99m)Tc-HYNIC-Trastuzumab as a Potential Radiopharmaceutical for In Vivo Evaluation of HER2 Expression in Breast Cancer.

PubMed

Calzada, Victoria; Garcia, Fernanda; Fernández, Marcelo; Porcal, Williams; Quinn, Thomas; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2013-01-01

The amplification of HER2 gene has been described in several tumor types, mainly breast cancer with a subsequent increase in HER2 protein expression. Trastuzumab is a humanized monoclonal antibody that recognizes selectively the HER2 extracellular domain. The objective of the present work was to standardize the conjugation of Trastuzumab with Succinimidyl-hydrazinonicotinamide (HYNIC) and labeling with (99m)Tc to obtain (99m)Tc-HYNIC-Trastuzumab for use as in vivo tracer of the HER2 expression in breast cancer. The labeling procedure involved derivatization of 0.067 μmol of Trastuzumab with 0.33 μmols of HYNIC in dimethyl sulfoxide (DMSO). The mixture was incubated for 30 min. A mixture of Tricine and SnCl2.2H2O was prepared by add a solution of 44.6 μmols Tricine in 0.05 mL HCl 2.0 M and a similar volume of another solution containing 44.3 μmols SnCl2.2H2O in 0.5 mL HCl 2.0 M. Then, 0.05 mL of this mixed was added to the conjugated with 296 MBq of 99mTcO-4. The final mixture was incubated at room temperature (18-25°C) for 30 min. Radiochemical purity of the labeled solution was studied by chromatography, to evaluate (99m)Tc-Tricine, (99m)TcO2.H2O, and free (99m)TcO4 (-). Radiochemical purity was also evaluated by HPLC. Stability studies were tested in solution at 4°C and lyophilized at 4°C. Biodistribution studies were performed in healthy CD-1 female mice at 2, 5, and 24 h (n = 3) and CD-1 female mice spontaneous breast adenocarcinoma (n = 3). Scintigraphic images of spontaneous breast adenocarcinoma in female CD-1 mice were acquired in a gamma camera at 2, 5, and 24 h post-injection. Labeling was easily performed with high yields (>90%) and radiopharmaceutical stability for 24 h post-labeling. Stability studies revealed that antibody derivative must be lyophilized for undamaged storage. Biodistribution studies and imaging revealed excellent uptake in the tumor. Based on the results it was concluded that (99m)Tc-HYNIC-Trastuzumab could be a promising radiopharmaceutical for in vivo diagnosis of the HER2 status in breast with impact on treatment planning.

Biokinetics and dosimetry in patients of 99mTc-EDDA/HYNIC-Tyr3-octreotide prepared from lyophilized kits.

PubMed

González-Vázquez, Armando; Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Gutiérrez-García, Zohar

2006-07-01

99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for 99mTc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after 99mTc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99mTc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3+/-0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv.

Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.

PubMed

Kaschwich, Mark; Lützen, Ulf; Zhao, Yi; Tjiong, Angelina; Marx, Marlies; Haenisch, Sierk; Wiedow, Oliver; Preuss, Stefanie; Culman, Juraj; Zuhayra, Maaz

2016-04-01

Elafin is a potent reversible inhibitor of the pro-inflammatory proteases leukocyte elastase and protease 3. It is currently in clinical development for the use in postoperative inflammatory diseases. We investigated the pharmacokinetics of (99m)Tc-labeled elafin ((99m)Tc-Elafin) in blood and individual organs in rat after bolus intravenous injection using the single photon emission tomography (SPECT). (99m)Tc-Elafin predominantly accumulated in the kidney reaching a maximum of 8.5% ± 0.1% of the injected dose per gram (ID/g) at 5 min post injection (p.i) and decreased only slowly during 24 h. In contrast, the initially high radio activity recorded in the other organs rapidly decreased parallel to the radioactivity detected in blood. The blood kinetics fits to a two compartment kinetics model. The radio activity in the dissected kidney was 4.98 ± 1.24%ID/g 24 h p.i, while in other organs, including the brain, no accumulation of (99m)Tc-Elafin was detected. At this time point 30% of the detected radioactivity in the kidney was identified to be not metabolized (99m)Tc-Elafin. In conclusion, the blood and organ-specific kinetic data provide a basis for planning of adequate dosing regimens and the high accumulation of intact elafin in the kidney favors clinical developments targeting inflammatory kidney diseases, such as chronic allograft nephropathy after kidney transplantation. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

The lymphoscintigraphic manifestation of (99m)Tc-dextran lymphatic imaging in primary intestinal lymphangiectasia.

PubMed

Wen, Zhe; Tong, Guansheng; Liu, Yong; Meeks, Jacqui K; Ma, Daqing; Yang, Jigang

2014-05-01

The aim of this study was to analyze the imaging characteristics of (99m)Tc-dextran ((99m)Tc-DX) lymphatic imaging in the diagnosis of primary intestinal lymphangiectasia (PIL). Forty-one PIL patients were diagnosed as having PIL with the diagnosis being subsequently confirmed by laparotomy, endoscopy, biopsy, or capsule colonoscopy. Nineteen patients were male and 22 were female. A whole-body (99m)Tc-DX scan was performed at 10 min, 1 h, 3 h, and 6 h intervals after injection. The 10 min and 1 h postinjection intervals were considered the early phase, the 3 h postinjection interval was considered the middle phase, and the 6 h postinjection interval was considered the delayed phase. The imaging characteristics of (99m)Tc-DX lymphatic imaging in PIL were of five different types: (i) presence of dynamic radioactivity in the intestine, associated with radioactivity moving from the small intestine to the ascending and transverse colon; (ii) presence of delayed dynamic radioactivity in the intestine, no radioactivity or little radioactivity distributing in the intestine in the early phase, or significant radioactivity distributing in the intestine in the delayed phase; (iii) radioactivity distributing in the intestine and abdominal cavity; (iv) radioactivity distributing only in the abdominal cavity with no radioactivity in the intestines; and (v) no radioactivity distributing in the intestine and abdominal activity. (99m)Tc-DX lymphatic imaging in PIL showed different imaging characteristics. Caution should be exercised in the diagnosis of PIL using lymphoscintigraphy. Lymphoscintigraphy is a safe and accurate examination method and is a significant diagnostic tool in the diagnosis of PIL.

Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

PubMed Central

Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

1998-01-01

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

Applicability of 99m Tc-Labeled Human Serum Albumin Scintigraphy in Dogs With Protein-Losing Enteropathy.

PubMed

Engelmann, N; Ondreka, N; von Pückler, K; Mohrs, S; Sicken, J; Neiger, R

2017-03-01

Diagnosis of protein loss into the gastrointestinal tract using noninvasive techniques is challenging. In people, scintigraphy not only is a sensitive tool to confirm protein-losing enteropathy (PLE), but it also allows for localization of protein loss. To investigate the feasibility of 99m Tc-labeled human serum albumin (HSA) scintigraphy in dogs with PLE in comparison with control dogs. A total of 8 clinically healthy control research dogs and 7 client-owned dogs with gastrointestinal clinical signs and hypoalbuminemia (serum albumin concentration <2.0 g/dL). Prospective case-control study. After IV injection of 400 MBq freshly prepared 99m Tc HSA (30 mg/dog), images of the abdomen were obtained 10, 60, 120, and 240 minutes postinjection. Additional images of the salivary and thyroid glands were obtained to rule out free 99m Tc. A scan was considered positive for PLE when radiopharmaceutical exudation was detectable in the intestinal tract. Only 1 control dog showed exudation of the radiopharmaceutical into the intestinal tract. No free 99m Tc was detected in any dog. In dogs with PLE, focal small intestinal and diffuse small intestinal radiopharmaceutical exudation into the bowel was detected in 2 and 3 dogs, respectively, whereas in 2 dogs, there was disagreement about whether radiopharmaceutical exudation was focal or diffuse. 99m Tc-labeled HSA scintigraphy was feasible to diagnose PLE in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Is prophylactic embolization of the hepatic falciform artery needed before radioembolization in patients with 99mTc-MAA accumulation in the anterior abdominal wall?

PubMed

Ahmadzadehfar, Hojjat; Möhlenbruch, Markus; Sabet, Amir; Meyer, Carsten; Muckle, Marianne; Haslerud, Torjan; Wilhelm, Kai; Schild, Hans Heinz; Biersack, Hans Jürgen; Ezziddin, Samer

2011-08-01

While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of (99m)Tc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours. A total of 224 diagnostic hepatic angiograms combined with (99m)Tc-MAA SPECT/CT were acquired in 192 patients with different types of cancer, of whom 142 were treated with a total of 214 radioembolization procedures. All patients received a whole-body scan, and planar and SPECT/CT scans of the abdomen. Only patients with extrahepatic (99m)Tc-MAA accumulation in the anterior abdominal wall were included in this study. Posttreatment bremsstrahlung SPECT/CT and follow-up results for at least 3 months served as reference standards. Tracer accumulation in the anterior abdominal wall was present in pretreatment (99m)Tc-MAA SPECT/CT images of 18 patients (9.3%). The HFA was found and embolized by radiologists before treatment in one patient. In the remaining patients radioembolization was performed without any modification in the treatment plan despite the previously mentioned extrahepatic accumulation. Only one patient experienced abdominal muscle pain above the navel, which started 24 h after treatment and lasted for 48 h without any skin changes. The remaining patients did not experience any relevant side effects during the follow-up period. Side effects after radioembolization in patients with tracer accumulation in the anterior abdominal wall on (99m)Tc-MAA scans indicating a patent HFA are neither common nor severe. Thus, there is no absolute need for prophylactic embolization of the HFA or modification of the treatment plan if the HFA is not detectable on angiography.

Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis.

PubMed

Sobal, Grazyna; Velusamy, Kavitha; Kosik, Siegfried; Menzel, Johannes; Hacker, Marcus; Pagitz, Maximilian

2016-06-01

In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs. The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method. In-vivo uptake of (99m)TcCS was evaluated in dogs (n=12, castrated males, 4-9years, with 15-51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only. In healthy control dogs we did not detect any specific uptake of (99m)TcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented. Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls. In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I-III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of (99m)TcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects. These results suggest that (99m)TcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status.

PubMed

Tu, Min-Chien; Lo, Chung-Ping; Chen, Ching-Yuan; Huang, Ching-Feng

2015-12-03

Cobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (<250 pg/ml). Twelve symptomatic patients with low serum Cbl status were enrolled. Clinical presentations, Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed. Dysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy. Our TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be seen in the earlier state of Cbl deficiency, when psychiatric symptoms predominate. Hypoperfusion beyond thalamus/basal ganglia and involving frontal regions appears when cognitive problems, mostly dysexecutive syndrome, are manifested. Symmetric hypofrontality of SPECT in the context of dysexcutive syndrome serves as a distinguishing feature of non-amnestic mild cognitive impairment attributed to Cbl deficiency. Concordant with TC-99 m-ECD SPECT findings, the psychiatric symptoms and dysexcutive syndrome undergird impaired limbic and dorsolateral prefrontal circuits originating from basal ganglia respectively.

99mTc-EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid tumours: results of 3 years' experience.

PubMed

Hubalewska-Dydejczyk, A; Fröss-Baron, K; Mikołajczak, R; Maecke, H R; Huszno, B; Pach, D; Sowa-Staszczak, A; Janota, B; Szybiński, P; Kulig, J

2006-10-01

At all stages of the disease, serious difficulties are encountered in the imaging diagnosis of carcinoids. Somatostatin receptor scintigraphy (SRS) holds great promise for detecting primary tumours and metastases. 99mTc-EDDA/HYNIC-octreotate should significantly improve the diagnosis of carcinoids in comparison with 111In-Octreoscan owing to the better affinity for SSR2 and the higher count rate. The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-octreotate scintigraphy in the detection and staging of carcinoid tumours. The study population comprised 75 patients (age 48.5+/-15.5 years): 46 with histological confirmation of carcinoid and 29 with suspected disease. 99mTc-EDDA/HYNIC-octreotate (740 MBq) SRS and CT were performed in all patients. Fifteen patients were examined with 111In-Octreoscan. High-quality 99mTc-EDDA/HYNIC-octreotate images were obtained in all cases, with maximum tumour tracer accumulation 4 h p.i. The mean target/non-target ratios for whole body (WB) and SPECT scans were, respectively, as follows: primary lesions: 4.5 and 10.2; metastases: liver, 3.1 and 12.3; abdominal focal lesions, 2.7 and 5.8; lung, 2.7 and 8.3; mediastinum, 3.4 and 7.6; bones, 6.8 and 19.0. 99mTc-EDDA/HYNIC-octreotate WB scans revealed more metastases than 111In-Octreoscan, with better individual separation. 99mTc-EDDA/HYNIC-octreotate SRS revealed new metastatic lesions in seven patients with confirmed carcinoid, and in four with dissemination the primary focus was found. Five patients qualified for radioguided surgery and 11 were referred to 90Y-DOTA-TATE therapy. The sensitivity of SRS in comparison with CT was higher for primary lesions and liver and abdominal lymph node metastases. In the subgroup of patients with suspected neuroendocrine tumours, two duodenal carcinoids, one thymic carcinoid and one ileal carcinoid were found. 99mTc-EDDA/HYNIC-octreotate, with high imaging quality, is an excellent alternative to 111In-Octreoscan for staging of carcinoids, and it seems to be the method of choice for detection of the primary focus in patients with metastases from an unknown primary tumour.

Synthesis, characterization and biological evaluation of a novel "3 + 1" mixed ligand 99mTc complex having an aliphatic thiol as coligand.

PubMed

Rey, A; Papadopoulos, M; Leon, E; Mallo, L; Pirmettis, Y; Manta, E; Raptopoulou, C; Chiotellis, E; Leon, A

2001-03-01

A novel "3 + 1" mixed ligand 99mTc complex with N,N-bis(2-mercaptoethyl)-N'N'-diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the labeling yield was over 80% and a major product with radiochemical purity >80% was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium and 99gTc complexes. Results were consistent with the expected "3 + 1" structure and X-ray diffraction study demonstrated that the complex adopted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretion through hepatobiliary system. Although brain/blood ratio increased significantly with time, this novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.

Technetium-99m(Sn2+)pyrophosphate in ischemic and infarcted dog myocardium in early stages of acute coronary occlusion: histochemical and tissue-counting comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bianco, J.A.; Kemper, A.J.; Taylor, A.

1983-06-01

We have investigated the pattern of accumulation of Tc-99m(Sn2+)pyrophosphate (Tc-99m PPi) in myocardial tissue of dogs during the early stages of acute occlusion of the left anterior descending coronary artery. Three groups were studied after: (a) 40 min occlusion followed by 6 hr reperfusion (n . 6); (b) 6 hr occlusion followed by one hour reperfusion (n . 5); and (c) 7 hr occlusion with no reperfusion (n . 4). Areas of myocardial infarction were defined with triphenyl-tetrazolium chloride (TTC) staining, and blood flow was determined with 9-mu radioactive microspheres. In Group C uptake in infarcted and peri-infarct areas wasmore » not enhanced, most likely owing to low flow. In Group B, with late reperfusion, Tc-99m PPi sequestration was increased in both infarcted and peri-infarcted tissues. In Group A, areas ischemic during occlusion but with normal flow and viability by TTC after 6 hr of reperfusion showed significant uptake of Tc-99m PPi (twice the uptake of nonischemic regions).« less

Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

PubMed

Wang, Xuejuan; Yang, Zhi; Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

2016-06-21

We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

Noninvasive evaluation of active lower gastrointestinal bleeding: comparison between contrast-enhanced MDCT and 99mTc-labeled RBC scintigraphy.

PubMed

Zink, Stephen I; Ohki, Stephen K; Stein, Barry; Zambuto, Domenic A; Rosenberg, Ronald J; Choi, Jenny J; Tubbs, Daniel S

2008-10-01

The purpose of our study was to compare contrast-enhanced MDCT and (99m)Tc-labeled RBC scanning for the evaluation of active lower gastrointestinal bleeding. Over 17 months, 55 patients (32 men, 23 women; age range, 21-92 years) were evaluated prospectively with contrast-enhanced MDCT using 100 mL of iopromide 300 mg I/mL. Technetium-99m-labeled RBC scans were obtained on 41 of 55 patients and select patients underwent angiography for attempted embolization. Each imaging technique was reviewed in a blinded fashion for sensitivity for detection of active bleeding as well as the active lower gastrointestinal bleeding location. Findings were positive on both examinations in eight patients and negative on both examinations in 20 patients. Findings were positive on contrast-enhanced MDCT and negative on (99m)Tc-labeled RBC in two patients; findings were negative on contrast-enhanced MDCT and positive on (99m)Tc-labeled RBC in 11 patients. Statistics showed significant disagreement, with simple agreement = 68.3%, kappa = 0.341, and p = 0.014. Sixteen of 60 (26.7%) contrast-enhanced MDCT scans were positive prospectively, with all accurately localizing the site of bleeding and identification of the underlying lesion in eight of 16 (50%). Nineteen of 41 (46.3%) (99m)Tc-labeled RBC scans were positive. Eighteen of 41 matched patients went on to angiography. In four of these 18 (22.2%) patients, the site of bleeding was confirmed by angiography, but in 14 of 18 (77.8%), the findings were negative. Contrast-enhanced MDCT and (99m)Tc-labeled RBC scanning show significant disagreement for evaluation of active lower gastrointestinal bleeding. Contrast-enhanced MDCT appears effective for detection and localization in cases of active lower gastrointestinal bleeding in which hemorrhage is active at the time of CT.

Assessment of alveolar epithelial permeability in Behçet's disease with 99mTc-DTPA aerosol scintigraphy.

PubMed

Gumuser, Fikriye G; Pirildar, Timur; Batok, Dilek; Sakar, Aysin; Ruksen, Ebru; Sayit, Elvan

2008-06-01

Behçet's disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1-10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid ((99m)Tc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible. Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67 +/- 8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87 +/- 12.45 years) underwent (99m)Tc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of (99m)Tc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 x 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of (99m)Tc-DTPA clearance (T (1/2)) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol. The clearance half time of (99m)Tc-DTPA radioaerosols in the BD patients (24.81 +/- 6.22 min) was faster than in the normal control group (46.53 +/- 22.41 min) (P = 0.004). There was also a significant difference between PI of the patients with BD (0.15 +/- 0.03) and that of the controls (0.21 +/- 0.06) (P = 0.002). No correlation was found between the mean T (1/2) values of (99m)Tc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PFT in the BD patients. Lung epithelial permeability of the patients with BD was significantly higher than that of the normal subjects. The results of this study demonstrated that the assessment of lung epithelial permeability using (99m)Tc-DTPA aerosol scintigraphy could predict the presence of lung involvement in the early stages of BD.

Nurse exposure doses resulted from bone scintigraphy patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

Tricine co-ligand improved the efficacy of 99mTc-HYNIC-(Ser)3-J18 peptide for targeting and imaging of non-small-cell lung cancer.

PubMed

Shaghaghi, Zahra; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

2018-05-15

The early diagnosis of non-small cell lung cancer (NSCLC) is important for increasing survival rate and improving quality life of patients. The aim of this study was to investigate 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 for targeting and imaging of NSCLC in A-549 xenografted nude mice. The (Ser) 3 -J18 peptide was conjugated with HYNIC and labeled with 99m  Tc using tricine as a co-ligand. The radiolabeled peptide was evaluated for its radiochemical purity, stability, receptor binding and internalization in vitro. The future experiments were performed for tumor targeting and imaging in A-549 tumor-bearing mice. 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 was obtained at high labeling efficiency at room temperature and favorable stability in saline and human plasma. At the cellular level, the radiolabeled peptide specifically bond to A-549 cells with a K D 4.1 ± 1.3 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 3.12 and 5.63 respectively after 2 h injection of radiolabeled peptide. These ratios were significantly decreased by co-injection of excess non-labeled peptide in mice. This radiolabeled peptide selectively targeted to NSCLC tumor and exhibited a high target uptake combined with acceptable low background activity for tumor imaging in mice. The results of this study and its comparison with another study showed that 99m  Tc-(tricine)-HYNIC-(Ser) 3 -J18 is better than previously reported radiolabeled peptide as 99m  Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 for NSCLC targeting and imaging. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

PubMed Central

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Methods: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID:27408857

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours.

PubMed

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement

PubMed Central

Lee, Hyunjong; Kim, Ji Hyun; Kang, Yeon-koo; Moon, Jae Hoon; So, Young; Lee, Won Woo

2016-01-01

Abstract Objectives: Technetium pertechnetate (99mTcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of 99mTcO4. Here, we investigated the usefulness of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) after injection of 99mTcO4 in detecting thyroid function abnormalities. Materials and methods: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 ± 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent 99mTcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. Results: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal–Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other 99mTcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. Conclusions: Quantitative SPECT/CT is more accurate than conventional TUS for measuring 99mTcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID:27399139

A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in graves' ophtalmopathy patients with different clinical activity score.

PubMed

Rebelo Pinto, E dos S; Lopes, F P P L; de Souza, S A L; da Fonseca, L M B; Vaisman, M; Gutfilen, B; dos Santos Teixeira, P de F

2013-09-01

The present study describes the preliminary results of the use of 99mTc-anti-TNF-α scintigraphy as a new diagnostic approach to evaluate patients presenting with Graves' ophthalmopathy (GO). Patients (n=25) presenting at different inflammatory stages of GO and 10 healthy volunteers underwent 99mTc-anti-TNF-α scintigraphy. Images were obtained 15 min after the intravenous injection of 370 MBq (10 mCi) 99mTc-anti-TNF-α. Planar images were obtained in a 256×256 matrix (each lasting 5 min) and single photon emission computed tomography (SPECT) scan lasting 13 min. Regions of interest (ROI) were drawn on the orbit and cerebral hemispheres. The uptake of 99m Tc-anti-TNF-α in these regions was compared and positive scintigraphy established when the ROI was >2.5. In addition, uptake for each positive exam was scored as either slight (2.6-5.1), moderate (5.2-7.6), or high (>7.6). In this pilot study, 69 orbits were evaluated (1 patient had only 1 eye), and 27 had a positive CAS (≥3/7). Scintigraphies were positive in 38 orbits. Comparing the results of the exams with CAS, a high sensitivity and negative predictive values were determined for scintigraphy (96.3% and 96.7%, respectively). However, the specificity and the positive predictive values were 71.4% and 68.4%, respectively, with an accuracy of 81.2%. The exclusion of examinations that were slightly positive from the analysis resulted in an improvement in test accuracy (95.5%). The preliminary results suggest that 99mTc-anti-TNF-α scintigraphy is a promising procedure for the evaluation of active orbital inflammation in GO. © Georg Thieme Verlag KG Stuttgart · New York.

Post-modification of preformed liposomes with novel non-phospholipid poly(ethylene glycol)-conjugated hexadecylcarbamoylmethyl hexadecanoic acid for enhanced circulation persistence in vivo

PubMed Central

Nag, Okhil K; Yadav, Vivek R; Hedrick, Andria; Awasthi, Vibhudutta

2013-01-01

We report synthesis and characterization of a novel PEG2000-conjugated hexadecylcarbamoylmethyl hexadecanoate (HDAS-PEG) as a PEG-phospholipid substitute for enhancing circulation persistence of liposomes. HDAS-PEG showed critical micelle concentration of 4.25 μM. We used post-insertion technique to introduce HDAS-PEG in outer lipid layer of the preformed liposomes. The presence of surface HDAS-PEG was confirmed by altered electrophoretic mobility, confocal microscopy and PEG estimation by ELISA. The post-inserted HDAS-PEG desorbed at approximately half the rate at which post-inserted DSPE-PEG desorbed from the liposome surface. HDAS-PEG significantly reduced liposome-induced complement activation (C4d, Bb and SC5b); HDAS-PEG was more effective than more commonly used DSPE-PEG in this capacity. For studying circulation persistence, the liposomes were labeled with 99mTc radionuclide and administered in rats. 99mTc-HDAS-PEG-liposomes showed prolonged persistence in blood as compared to that shown by 99mTc-plain liposomes. After 24 h of administration, < 1% of 99mTc-plain liposomes remained in blood, whereas approximately 28% of injected 99mTc-HDAS-PEG-liposomes were present in blood. In comparison, only 4.8% of 99mTc-DSPE-PEG-liposomes was measured in blood after 24 h. As expected, the clearance route of the liposomes was through liver and spleen. These results demonstrate the potential of a novel non-phosphoryl HDAS-PEG for surface modification of preformed liposomes with a goal of prolonging their circulation persistence and more effective inhibition of complement activation. PMID:23419666

Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.

PubMed

Gong, Wei; Dou, Huan; Liu, Xianqin; Sun, Lingyun; Hou, Yayi

2012-10-01

1. In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99)Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. 2. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. 3. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 μg/mL, (99)Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99)Tc-MDP abolished the appearance of multinucleated osteoclasts. 4. Real-time RT-PCR analysis of transcription factor expression revealed that (99)Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99)Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. Finally, (99)Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. 5. In conclusion, (99)Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

Osteomalacia-inducing renal clear cell carcinoma uncovered by 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) scintigraphy.

PubMed

Jin, Xiaona; Jing, Hongli; Li, Fang; Zhuang, Hongming

2013-11-01

Most osteomalacia-causing tumors are small, benign mesenchymal neoplasms, which are commonly located in the extremities or craniofacial regions. An 18-year-old male patient with suspicion of tumor-induced osteomalacia underwent (99m)Tc-HYNIC-TOC scintigraphy to search potential culprit tumor. The images showed a large activity in the region of the left kidney. The lesion was resected and a clear cell renal cell carcinoma was found. One year after the left nephrectomy, the patient was tumor-free without symptoms of osteomalacia.

Imaging, biodistribution and in vitro study of smart 99mTc-PAMAM G4 dendrimer as novel nano-complex.

PubMed

Narmani, Asghar; Yavari, Kamal; Mohammadnejad, Javad

2017-11-01

Overexpression of folic acid receptor in various human tumors cells makes it as good candidate for targeting delivery of chemotherapeutic and radiopharmaceutical agents. In this research, FA used for functionalization of PEG modified PAMAM G4 dendrimer as a smart delivery of 5-FU and 99m Tc for the breast carcinoma in order to chemotherapeutic and imaging goals. One aim of this research was assess the FA-mediated cell viability assay of PEG-PAMAM G4-FA-5FU- 99m Tc and in vitro uptake of PEG-PAMAM G4-FA- 99m Tc as the novel nano-complex determined on C2Cl2 (normal cell) and MCF-7 (breast cancer cell) cell lines. Other main goals were studied. Morover, an investigation in to in vivo imaging and biodistribution was carried out via a novel radio tracer by which tumor accumulation and site were obviously detected. The targeted tumor images taken by tail intravenous injection demonstrated that nano-complex can be smartly used in imaging study of the clinical practices. Also, the biodistribution of this nano-complex was investigated and the organ predestination of 99m Tc labeled nano-complex (%ID/g) was ascertained. Copyright © 2017 Elsevier B.V. All rights reserved.

The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

NASA Astrophysics Data System (ADS)

Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

2016-03-01

The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

PubMed

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

Measurement and Estimation of the 99Mo Production Yield by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Minato, Futoshi; Tsukada, Kazuaki; Sato, Nozomi; Watanabe, Satoshi; Saeki, Hideya; Kawabata, Masako; Hashimoto, Shintaro; Nagai, Yasuki

2017-11-01

We, for the first time, measured the yield of 99Mo, the mother nuclide of 99mTc used in nuclear medicine diagnostic procedures, produced by the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The neutrons with a continuous energy spectrum from the thermal energy up to about 40 MeV were provided by the C(d,n) reaction with 40 MeV deuteron beams. It was proved that the 99Mo yield agrees with that estimated by using the latest data on neutrons from the C(d,n) reaction and the evaluated cross section of the 100Mo(n,2n)99Mo reaction given in the Japanese Evaluated Nuclear Data Library. On the basis of the agreement, a systematic calculation was carried out to search for an optimum condition that enables us to produce as much 99Mo as possible with a good 99Mo/100Mo value from an economical point of view. The calculated 99Mo yield from a 150 g 100MoO3 sample indicated that about 30% of the demand for 99Mo in Japan can be met with a single accelerator capable of 40 MeV, 2 mA deuteron beams. Here, by referring to an existing 18F-fluorodeoxyglucose (FDG) distribution system we assumed that 99mTc radiopharmaceuticals formed after separating 99mTc from 99Mo can be delivered to hospitals from a radiopharmaceutical company within 6 h. The elution of 99mTc from 99Mo twice a day would meet about 50% of the demand for 99Mo.

Separation of [(99m)Tc]pertechnetate and molybdate using polyethylene glycol coated C18 and C30 resins.

PubMed

Andersson, J D; Wilson, J S; Romaniuk, J A; McEwan, A J B; Abrams, D N; McQuarrie, S A; Gagnon, K

2016-04-01

Hydrophobic adsorbents such as C18 and C30 were coated with PEG and subsequently used for the separation of Mo/Tc. The most effective resin for adsorbing PEG was the C18-U resin, which demonstrated a coating capacity of 97.6±2.8mg PEG per g of resin. The ability to adsorb pertechnetate was proportional to the amount of PEG coated on the hydrophobic resin. The [(99m)Tc]pertechnetate recovery during the separation of cyclotron produced (99m)Tc from (100)Mo was 91.8±0.3% (n=2). The resultant product met relevant USP monograph specifications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Removal of heavy metals from aqueous systems with thiol functionalized superparamagnetic nanoparticles.

PubMed

Yantasee, Wassana; Warner, Cynthia L; Sangvanich, Thanapon; Addleman, R Shane; Carter, Timothy G; Wiacek, Robert J; Fryxell, Glen E; Timchalk, Charles; Warner, Marvin G

2007-07-15

We have shown that superparamagnetic iron oxide (Fe3O4) nanoparticles with a surface functionalization of dimercaptosuccinic acid (DMSA) are an effective sorbent material for toxic soft metals such as Hg, Ag, Pb, Cd, and Tl, which effectively bind to the DMSA ligands and for As, which binds to the iron oxide lattices. The nanoparticles are highly dispersible and stable in solutions, have a large surface area (114 m2/g), and have a high functional group content (1.8 mmol thiols/g). They are attracted to a magnetic field and can be separated from solution within a minute with a 1.2 T magnet. The chemical affinity, capacity, kinetics, and stability of the magnetic nanoparticles were compared to those of conventional resin based sorbents (GT-73), activated carbon, and nanoporous silica (SAMMS) of similar surface chemistries in river water, groundwater, seawater, and human blood and plasma. DMSA-Fe3O4 had a capacity of 227 mg of Hg/g, a 30-fold larger value than GT-73. The nanoparticles removed 99 wt% of 1 mg/L Pb within a minute, while it took over 10 and 120 min for Chelex-100 and GT-73 to remove 96% of Pb.

Real-time gamma imaging of technetium transport through natural and engineered porous materials for radioactive waste disposal.

PubMed

Corkhill, Claire L; Bridge, Jonathan W; Chen, Xiaohui C; Hillel, Phil; Thornton, Steve F; Romero-Gonzalez, Maria E; Banwart, Steven A; Hyatt, Neil C

2013-12-03

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of (99)Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in (99m)Tc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ~20 MBq (99m)Tc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min(-1). Changes in calibrated mass distribution of (99m)Tc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection-dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that (99)Tc in the pertechnetate form (Tc(VII)O4(-)) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments.

Real-Time Gamma Imaging of Technetium Transport through Natural and Engineered Porous Materials for Radioactive Waste Disposal

PubMed Central

2013-01-01

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of 99Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in 99mTc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ∼20 MBq 99mTc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min–1. Changes in calibrated mass distribution of 99mTc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection–dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that 99Tc in the pertechnetate form (Tc(VII)O4–) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments. PMID:24147650

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

PubMed Central

Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2011-01-01

ABSTRACT Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract. PMID:21552677

Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species.

PubMed

Tisato, Francesco; Bolzati, Cristina; Refosco, Fiorenzo; Porchia, Marina; Seraglia, Roberta; Carta, Davide; Pasqualini, Roberto

2012-04-01

The neutral complex [(99m)Tc(N)(NOEt)(2)], often referred to as TcN-NOET [NOEt=N-ethoxy,N-ethyldithiocarbamate(1-)], was proposed several years ago as a myocardial imaging agent. Despite some favorable clinical properties evidenced during phase I and phase II studies, the overall results of the European and American phase III clinical studies have been judged insufficient for a successful approval process by the regulatory agencies. Non-carrier-added and carrier-added experiments using short-lived (99m)Tc and long-lived (99g)Tc have been utilized to prepare a series of bis-substituted [Tc(N)(DTC)(2)] complexes [DTC=dithiocarbamate(1-)]. They have been purified by means of chromatographic techniques (high-performance liquid chromatography and thin-layer chromatography) and identified via double detection (UV-vis and radiometry) by comparison with authenticated samples of (99g)Tc compounds prepared by conventional coordination chemistry procedures. The molecular structure of the lipophilic, neutral complex cis-[Tc(N)(NOEt)(2)] has been assigned by comparison with similar nitrido-Tc(V) complexes already reported in the literature. Novel bis-substituted nitrido-Tc complexes containing hydrolyzed portions of coordinated NOEt, namely, N-ethyldithiocarbamate [NHEt(1-)] and N-hydroxy, N-ethyldithiocarbamate [NOHEt(1-)], have been prepared and characterized by means of multinuclear nuclear magnetic resonance spectroscopy and mass spectrometry. Despite the identification of these "hydrolyzed" species, it is still unclear whether the failure to reach the clinical goal of the perfusion tracer [(99m)Tc(N)(NOEt)(2)] is related to the degradation processes evidenced in this study or is the result of the mediocre imaging properties of the tracer. Copyright © 2012 Elsevier Inc. All rights reserved.

WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taborda, A; Benabdallah, N; Desbree, A

2015-06-15

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres ofmore » unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.« less

[Situation of supply and boom of PET imaging: what is the future for technetium-99m in nuclear medicine?].

PubMed

Maia, S; Ayachi Hatit, N; Paycha, F

2011-05-01

Molecular imaging has shown its interest in the diagnosis, staging and therapy monitoring of many diseases, especially in the field of cancer. This imaging modality can detect non-invasively early molecular changes specific to these diseases. Its expansion includes two aspects linked firstly with the advanced techniques of imaging modalities and secondly with the development of tracers as radio pharmaceuticals for imaging new molecular targets. Technetium-99m ((99m)Tc), because of its physical characteristics, its widespread availability and low cost, is the most used radionuclide in molecular imaging with the technique of single photon emission computed tomography (SPECT). Nevertheless, the current difficulty concerning the supply and the great interest of Positron Emission Tomography (PET), the "competitor" imaging modality-using molecules labelled with fluorine-18 ((18)F), legitimates the question about the future of (99m)Tc, its supremacy and the emergence of new tracer labelled with (99m)Tc. Focusing on the actual and future supply situation, the place of SPECT imaging in nuclear medicine, as well as the development of new molecules labelled with (99m)Tc is necessary to show that this radionuclide will remain essential for the speciality in the next years. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Wear measurement using radioactive tracer technique based on proton, deuteron and α-particle induced nuclear reactions on molybdenum

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.

2012-11-01

Excitation functions of light ion induced nuclear reactions on natural molybdenum have been studied in the frame of a systematic investigation of charged particle induced nuclear reactions on metals for various applications. Excitation functions of 93,94g,94m,95g,95m,96,99mTc, 90,93m,99Mo, 90,91m,92m,95m,95g,96Nb and 88,89Zr were measured up to 50 MeV deuteron energy Tárkányi et al., 2012 [1], 93m,93g,94m,94g,95m,95g,96g,99mTc, 90,93m,99Mo, 90,92m,95m,95g,96Nb and 88,89Zr were measured up to 40 MeV proton energy Tárkányi et al., 2012 [2] and 93m,93g,94m,94g,95m,95g,96g,99mTc, 93m,99Mo, 90Nb, 94,95,97,103Ru and 88Zr were measured up to 40 MeV alpha energy Ditrói et al., 2012 [3] by using the stacked foil technique and activation method. The results for 3He induced reactions on natural Mo were taken from the literature Comparetto and Qaim, 1980 [4]. According to their half-lives, from the above listed radionuclides the 95m,96Tc, 91m,92m,95m,95gNb, 99Mo, 103,97Ru and 88Zr are suitable candidates for wear measurement by using thin layer activation (TLA) method. The goal of this work was to determine the necessary nuclear data for TLA of the above radionuclides and to prove their applicability for wear measurements.

99Tc and Re incorporated into metal oxide polyoxometalates: oxidation state stability elucidated by electrochemistry and theory.

PubMed

McGregor, Donna; Burton-Pye, Benjamin P; Mbomekalle, Israel M; Aparicio, Pablo A; Romo, Susanna; López, Xavier; Poblet, Josep M; Francesconi, Lynn C

2012-08-20

The radioactive element technetium-99 ((99)Tc, half-life = 2.1 × 10(5) years, β(-) of 253 keV), is a major byproduct of (235)U fission in the nuclear fuel cycle. (99)Tc is also found in radioactive waste tanks and in the environment at National Lab sites and fuel reprocessing centers. Separation and storage of the long-lived (99)Tc in an appropriate and stable waste-form is an important issue that needs to be addressed. Considering metal oxide solid-state materials as potential storage matrixes for Tc, we are examining the redox speciation of Tc on the molecular level using polyoxometalates (POMs) as models. In this study we investigate the electrochemistry of Tc complexes of the monovacant Wells-Dawson isomers, α(1)-P(2)W(17)O(61)(10-) (α1) and α(2)-P(2)W(17)O(61)(10-) (α2) to identify features of metal oxide materials that can stabilize the immobile Tc(IV) oxidation state accessed from the synthesized Tc(V)O species and to interrogate other possible oxidation states available to Tc within these materials. The experimental results are consistent with density functional theory (DFT) calculations. Electrochemistry of K(7-n)H(n)[Tc(V)O(α(1)-P(2)W(17)O(61))] (Tc(V)O-α1), K(7-n)H(n)[Tc(V)O(α(2)-P(2)W(17)O(61))] (Tc(V)O-α2) and their rhenium analogues as a function of pH show that the Tc-containing derivatives are always more readily reduced than their Re analogues. Both Tc and Re are reduced more readily in the lacunary α1 site as compared to the α2 site. The DFT calculations elucidate that the highest oxidation state attainable for Re is VII while, under the same electrochemistry conditions, the highest oxidation state for Tc is VI. The M(V)→ M(IV) reduction processes for Tc(V)O-α1 are not pH dependent or only slightly pH dependent suggesting that protonation does not accompany reduction of this species unlike the M(V)O-α2 (M = (99)Tc, Re) and Re(V)O-α1 where M(V/IV) reduction process must occur hand in hand with protonation of the terminal M═O to make the π*(M═O) orbitals accessible to the addition of electrons. This result is consistent with previous extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) data that reveal that the Tc(V) is "pulled" into the -α1 framework and that may facilitate the reduction of Tc(V)O-α1 and stabilize lower Tc oxidation states. This study highlights the inequivalency of the two sites, and their impact on the chemical properties of the Tc substituted in these positions.

Cyclic-RGD penta-peptides cRGDyK derivatized with cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes.

PubMed

Nadeem, Qaisar; Shen, Yunjun; Warsi, Muhammad Farooq; Nasar, Gulfam; Qadir, Muhammad Abdul; Alberto, Roger

2017-07-01

The present study reports the syntheses of half-sandwich complexes of the type [M(η 5 -C 5 H 4 CONH-R)(CO) 3 ] (M═Re, 99m Tc;R═cyclic RGD peptide (cRGDyK) for potential imaging of α v β 3 integrin expression. The 99m Tc complex was prepared directly from the reaction of [ 99m Tc(OH 2 ) 3 (CO) 3 ] + with cRGDyK, doubly conjugated to Thiele's acid [(C 5 H 5 COOH) 2 ] in water. This approach extends the viability of metal-mediated retro Diels-Alder reactions for the preparation of small molecules such as linear tripeptides to a more complex cyclic peptide carrying a [(η 5 -C 5 H 4 ) 99m Tc(CO) 3 ] tag. The Diels-Alder product [(C 5 H 5 CONH-cRGDyK) 2 ] was prepared from Thiele's acid via double peptide coupling. The Re-complex [Re(η 5 -C 5 H 4 CONH-cRGDyK)(CO) 3 ] was obtained by attaching [Re(η 5 -C 5 H 4 COOH)(CO) 3 ] directly to the N-terminus of cRGDyK. The identity of the 99m Tc-complex is confirmed by chromatographic comparison with the corresponding rhenium complex, fully characterized by spectroscopic techniques. Copyright © 2017 John Wiley & Sons, Ltd.

Evaluation of the effects of toluene inhalation on alveolar epithelial permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.

PubMed

Cerci, Sevim Sureyya; Ozturk, Onder; Sutcu, Recep; Ozbek, Feride Meltem; Baydar, Cetin Lutfi; Yildiz, Mustafa; Akkaya, Ahmet; Delibas, Namk

2008-01-01

The main component of paint thinner used in industry is toluene diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed workers. To investigate the effect of TDI on 99mTc clearance rate of alveolar epithelium and on pulmonary function tests (PFT) in automobile painters, and to determine the relationship between 99mTc-DTPA radioaerosol lung scintigraphy and serum levels of antioxidant enzymes and metalloproteinases (MMPs) of automobile painters. Twenty-eight automobile painters and 13 control subjects were included in the study. 99mTc-DTPA aerosol inhalation scintigraphy and PFT were administered to all subjects. Clearance half-time (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and metalloproteinases were measured. The mean T1/2 values of automobile painters were longer in both smoker and non-smoker subjects, but the difference was not significant (P>0.05). Although the PFT values decreased in automobile painters, there was no significant difference between each group. Any correlation between spirometric measurements and T1/2 or PI values in non-smoking automobile painters was not detected. Negative correlation among mean T1/2 value and FVC% and FEV1% in smoking automobile painters, and positive correlation between mean T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were detected. Our results suggested that the clearance of 99mTc-DTPA from the lungs of automobile painters was slower than in the control group, but the difference is not statistically significant. This data also supports the observation that TDI occasionally stimulates bronchial changes rather than alveolar changes in automobile painters.

[Screening with angiographic images prior to (99m)Tc-HMPAO labelled leukocyte scintigraphy in the diagnosis of periprosthetic infection].

PubMed

Granados, U; Fuster, D; Soriano, A; García, S; Bori, G; Martínez, J C; Mayoral, M; Perlaza, P; Tomás, X; Pons, F

2015-01-01

To evaluate the impact of the angioscintigrapy of the three phase bone scan as screening method to rule out infection of the hip and knee prosthesis prior to performing the (99m)Tc-HMPAO leukocyte scintigraphy. A total of 120 (70 women, 50 men; mean age 71±11years) with clinical suspicion of hip (n=63) or knee (n=57) infection of the prosthesis and clinical suspicion of infection were evaluated prospectively. All patients underwent three-phase bone scan (angioscintigraphy, vascular and bone phase) and (99m)Tc-HMPAO-labelled white blood cell scintigraphy. Final diagnosis of infection was made by microbiological documentation or clinical follow-up for at least 12months. Eighteen out of 120 patients were diagnosed of infection of hip prosthesis (n=10) or knee prosthesis (n=8). The angioscintigraphy was positive in 15/18 infected cases and in 21/102 of the non-infected cases with a sensitivity of 83%, specificity of 79% and negative predictive value of 97%. Sensitivity and specificity of (99m)Tc-HMPAO leukocyte scintigraphy were 72% and 95%, respectively. If the leukocyte labeled scintigraphies had been used exclusively for patients with positive angioscintigraphy, this would have saved up to 70% of the (99m)Tc-HMPAO leukocyte scintigraphies performed. There were no cases of infection with positive labeled leukocyte scintigraphy and negative angioscintigraphy. Angioscintigraphy (blood flow phase of bone scan) is a useful technique for screening for hip and knee joint prosthesis infection, significantly reducing the need for (99m)Tc-HMPAO leukocyte scintigraphy without affecting the sensitivity of the technique. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

99mTc ovalbumin labelled eggs for gastric emptying scintigraphy: in-vitro comparison of solid food markers.

PubMed

Blanc, Frédérique; Salaun, Pierre Y; Couturier, Olivier; Querellou, Solène; Le Duc-Pennec, Alexandra; Mougin-Degraef, Marie; Bizais, Yves; Legendre, Jean M

2005-11-01

The reliability of solid phase gastric emptying measurements by scintigraphy requires a marker that remains within the solid component of the test meal, and which is not degraded by the gastric juice throughout the scintigraphic procedure. In Europe, foods are most often labelled with 99mTc rhenium sulfide macrocolloid (RSMC) but this solid phase marker was withdrawn from the market in January 2004. To test other potential solid phase markers and to compare them to the reference marker RSMC. These markers were rhenium sulfide nanocolloid (RSNC), tin fluoride colloid (TFC), phytates and two albumins (Alb and AlbC). All were radiolabelled with 99mTc. After quality control, each 99mTc marker was incorporated into the albumin of one egg. Then, egg white and yolk were mixed together, and a well-cooked omelette was prepared. Aliquots of the omelette were incubated with an acidic solution of pepsin at 37 degrees C which mimicked gastric juice. Unbound radioactivity in the supernatant fraction was measured at various times up to 3 h. The radiochemical purity was > 95% for all radiopharmaceuticals. During the in-vitro incubation, the percentage of 99mTc labelled colloids released from the omelette increased continuously: after 3 h, 5% for TFC and RSMC, 8% for phytates, and > 9% for the two albumins and RSNC. Considering quality controls and release of 99mTc during in-vitro incubation of the omelette, TFC showed the same behaviour as the reference marker RSMC. Thus, TFC seems to be the best candidate to replace RSMC for the radiolabelling of the solid phase of the gastric emptying test meal.

Isothiocyanate-functionalized bifunctional chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) complexes for targeting uPAR in prostate cancer

USDA-ARS?s Scientific Manuscript database

Developing strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors is a growing realm in radiopharmaceutical development. This work presents the preparation of a novel isothiocyanate-functionalized bifunctional chelate based on 2,2´-dipicolylamine ...

Role of nuclear medicine in clinical urology and nephrology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blaufox, M.D.; Fine, E.; Lee, H.B.

The application of radionuclide studies to nephrologic and urologic practice has reached a measurable degree of maturity during the past several years. In spite of this, the utilization of these techniques in many institutions in the United States continues to be far less frequent than one would expect from the clinical advantages. The aim of this editorial is to try to place the role of nuclear medicine in urology and nephrology in perspective. At the present time, in spite of the large number of renal agents that have been developed, there is no practical ideal radiopharmaceutical that can serve asmore » a universal agent. Arbitrarily, one may reduce the chief armamentarium to only four radiopharmaceuticals; technetium-99m DTPA, I-131 OIH (orthoiodohippurate), technetium-99m glucoheptonate and technetium-99m DMSA. These agents are discussed with their relative advantages and disadvantages.« less

[Renal excretion of methylene-diphosphate-technium-99m. Preliminary observations].

PubMed

Vattimo, A; Martini, G

1983-11-30

The purpose of this study is to elucidate the mechanism of the renal excretion of 99mTc-MDP in man. We compared the renal clearance of 99mTc-MDP and 51Cr-EDTA (glomerular filtration rate agent). Since the 99mTc-MDP is bound to the plasma protein, the free fraction was calculated by dialysis. The clearances were obtained by single-injection technique. The plasma disappearance of the tracers was resolved into three exponential functions and area was calculated. The clearance was calculated by dividing the amount of the tracers excreted during the first four hours and the plasma area. In this study no difference was found in the clearance of the two agents. These findings suggest that the renal excretion of diphosphonate is related to the glomerular filtration rate.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation.

PubMed

Meads, C; Sutton, A; Małysiak, S; Kowalska, M; Zapalska, A; Rogozinska, E; Baldwin, P; Rosenthal, A; Ganesan, R; Borowiack, E; Barton, P; Roberts, T; Sundar, S; Khan, K

2013-12-01

Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. The National Institute for Health Research Health Technology Assessment programme.

Simultaneous Tc-99m and I-123 dual-radionuclide imaging with a solid-state detector-based brain-SPECT system and energy-based scatter correction.

PubMed

Takeuchi, Wataru; Suzuki, Atsuro; Shiga, Tohru; Kubo, Naoki; Morimoto, Yuichi; Ueno, Yuichiro; Kobashi, Keiji; Umegaki, Kikuo; Tamaki, Nagara

2016-12-01

A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I-lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 ± 4.0 % (mean ± standard deviation). In the six-compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 ± 11.0 and 2.3 ± 1.8 %, respectively. In the volunteer study, the PD between the single and dual acquisitions was 4.5 ± 3.4 %. This CdTe-SPECT system using the FiveEW method can provide accurate simultaneous dual-radionuclide imaging. A solid-state detector SPECT system using the FiveEW method will permit quantitative simultaneous Tc-99m and I-123 study to become clinically applicable.

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

PubMed

Schmidkonz, Christian; Hollweg, Claudia; Beck, Michael; Reinfelder, Julia; Goetz, Theresa I; Sanders, James C; Schmidt, Daniela; Prante, Olaf; Bäuerle, Tobias; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-01-01

99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score. © 2017 Wiley Periodicals, Inc.

Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in Porcine Model of Post-Infarct Remodeling: Relationship to Myocardial Dysfunction

PubMed Central

Sahul, Zakir H.; Mukherjee, Rupak; Song, James; McAteer, Jarod; Stroud, Robert E.; Dione, Donald P.; Staib, Lawrence; Papademetris, Xenophon; Dobrucki, Lawrence W.; Duncan, James S.; Spinale, Francis G.; Sinusas, Albert J.

2011-01-01

Background Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction post MI remains undefined. Methods and Results MI was surgically induced in pigs (n=23) and cine MR and dual isotope hybrid SPECT/CT imaging obtained using thallium-201 (201Tl) and a technetium-99m labeled MMP targeted tracer (99mTc-RP805) at 1, 2 and 4 weeks post MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial 99mTc-RP805 retention. MMP activation as assessed by in vivo and ex vivo 99mTc-RP805 imaging/retention studies was increased nearly 5-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e0.48x, p=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional 99mTc-RP805 uptake and ex vivo MMP-2 activity. Conclusions A novel, multimodality non-invasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased 99mTc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of 201Tl perfusion. 99mTc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling. PMID:21505092

Egg labeling methods for gastric emptying scintigraphy are not equivalent in producing a stable solid meal.

PubMed

Knight, Linda C; Kantor, Steven; Doma, Siva; Parkman, Henry P; Maurer, Alan H

2007-11-01

A wide range of radiolabeled test meals have been used for gastric emptying scintigraphy. The purpose of this study was to test whether (99m)Tc-sulfur colloid-labeled liquid egg white is as stable as 2 fresh whole eggs labeled with (99m)Tc-sulfur colloid and whether the cooking method is important. Whole eggs and liquid egg white were mixed with (99m)Tc-sulfur colloid and cooked by either microwaving or frying on a griddle. The cooked eggs were tested for breakdown after 2 and 4 h of incubation in gastric fluid or HCl. Labeled liquid egg white, prepared by either method of cooking, exhibited less breakdown in gastric fluid than whole eggs. Whole eggs cooked in the microwave exhibited significantly more breakdown than liquid egg white. (99m)Tc-Sulfur colloid binds better to egg whites compared with whole eggs. These results emphasize the need to evaluate the stability of new radiolabeled test meal preparations, including the method of cooking.

Physiological expression of pancreatic somatostatin receptors in 99mTc-HYNIC-TOC scintigraphy.

PubMed

de la Cueva, L; Lloro, P; Sangrós, M J; López Vélez, L; Navarro, P; Sarria, L; Álvarez, S; Abós, D

2017-07-01

To describe the frequency of head and/or pancreas uncinate process uptake of 99mTc-HYNIC-TOC, to study its nature, and analyze its diagnostic value. Retrospective evaluation of 47 consecutive 99mTc-HYNIC-TOC examinations was conducted. Head and/or pancreas uncinate process uptake was considered to be physiological in patients with normal CT at the same episode and in follow-up. It was analyzed if age or diabetes mellitus was justifying the existence or not of uptake. 32.5% patients showed uptake; 73% of them were mild. 84.6% patients with uptake have no pathology and 4% had neuroendocrine pancreatic disease at CT. Neither the age nor the diabetes mellitus established differences in patients without lesion. Near one-third of patients show physiological uptake by head and/or pancreas uncinate process at 99mTc-HYNIC-TOC scintigraphy. It seems that neither the diabetes nor the ages are factors that determine this physiological uptake.

Synthesis of 99mTc-nimotuzumab with tricarbonyl ion: in vitro and in vivo studies.

PubMed

Garcia, Maria Fernanda; Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Porcal, Williams; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2012-01-01

The Epidermal growth factor receptor (EGFR) family plays an important role in carcinogenesis. CIMAher® (Nimotuzumab), is a humanized monoclonal antibody, which recognizes EGFR with high affinity. The aim of this work was to perform the direct labeling of Nimotuzumab with [99mTc(CO)3(H2O)3]+ as precursor and to evaluate its labeling conditions, in vitro and in vivo stability and biodistrution in normal C57 BL/6J mice. 99mTc(CO3)-Nimotuzumab labeling yields were up to 90%. More than 90% of the complex remained intact after 24 h of incubation with L-Histidine (1/300 molar ratio). Biodistribution studies in normal mice were also performed. Inmunoreactivity was confirmed by cell binding assays with A431cells. These results encourage the evaluation of the potential role of 99mTc(CO)3-Nimotuzumab as a novel tumor-avid radiotracer for targeting in vivo EGFR expression.

Bone accumulation of the Tc-99m complex of carbamyl phosphate and its analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosain, P.; Spencer, R.P.; Ahlquist, K.J.

1978-05-01

Carbamyl phosphate, an organic moecule containing a single phosphate group, has been used in the therapy of sickle-cell disease. Carbamyl phosphate bound Tc-99m and achieved bone uptake in mice, rabbits, and a human volunteer. By examination of the structural formula, a working hypothesis was developed that predicted that the Tc-99m complexes of the analogous compounds acetyl phosphate, propionyl phosphate, and butyryl phosphate, each carrying single phosphate and carbonyl groups, would also show bone specificity. This was confirmed experimentally. Phosphonoacetic acid is a structural analog of these compounds. The structural analysis also predicted that aminomethylphosphonic acid and phosphoenolpyruvate would not havemore » as avid bone affinity, and this was also confirmed. These compounds represent a new class of bone-seeking agents that have the common properties of a lone phosphate and a carbonyl function. Such agents may permit the synthesis of additional analogs in an effort to obtain optimal affinity in the Tc-99m complexes.« less

[99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo: preparation and pre-clinical evaluation.

PubMed

Babaei, Mohammad Hossein; Almqvist, Ylva; Orlova, Anna; Shafii, Mohammad; Kairemo, Kalevi; Tolmachev, Vladimir

2005-06-01

Expression of epidermal growth factor receptors (EGFR) has prognostic and predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo may give valuable diagnostic information. The epidermal growth factor (EGF), a natural ligand, is a possible candidate for the targeting of EGFR. The present study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine-3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells with nanomolar affinity, and demonstrated good intracellular retention. The complex with EDDA demonstrated much higher stability in blood serum and during cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR expression in vivo.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Sui, E-mail: sshen@uabmc.edu; Jacob, Rojymon; Bender, Luvenia W.

Radiotherapy or stereotactic body radiosurgery (SBRT) requires a sufficient functional liver volume to tolerate the treatment. The current study extended the work of de Graaf et al. (2010) [3] on the use of {sup 99m}Tc-mebrofenin imaging for presurgery planning to radiotherapy planning for liver cancer or metastases. Patient was immobilized and imaged in an identical position on a single-photon emission computed tomography/computed tomography (SPECT-CT) system and a radiotherapy simulation CT system. {sup 99m}Tc-mebrofenin SPECT was registered to the planning CT through image registration of noncontrast CT from SPECT-CT system to the radiotherapy planning CT. The voxels with higher uptake ofmore » {sup 99m}Tc-mebrofenin were transferred to the planning CT as an avoidance structure in optimizing a 2-arc RapidArc plan for SBRT delivery. Excellent dose coverage to the target and sparing of the healthy remnant liver volume was achieved. This report illustrated a procedure for the use of {sup 99m}Tc-mebrofenin SPECT for optimizing radiotherapy for liver cancers and metastases.« less

Recycle of enriched Mo targets for economic production of 99Mo/ 99mTc medical isotope without use of enriched uranium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tkac, Peter; Vandegrift, George F.

2015-08-09

A new recycle process for recovery of enriched 98Mo or 100Mo used for production of 99Mo/ 99mTc medical isotope was developed. In this process, Mo is precipitated from spent NorthStar Mo/Tc generator solution containing ~200 g/L Mo as K 2MoO 4 in 5 M KOH using acetic acid and then washed with nitric acid. High purification factors from potassium were achieved, and typical Mo recovery yields were ~95 %. In conclusion, the recycle process was performed with up to 260 g of Mo per batch and can be easily implemented for processing of up to 400 g of Mo.

The use of technetium-99m-labeled human serum albumin diethylenetriamine pentaacetic acid single-photon emission CT scan in the follow-up of type II endoleak treatment.

PubMed

Nakai, Motoki; Sato, Hirotatsu; Ikoma, Akira; Sonomura, Tetsuo; Sato, Morio

2014-03-01

An 84-year-old woman presented with persistent type II endoleak with sac expansion from 57 mm to 75 mm during 4-year follow-up after endovascular abdominal aortic aneurysm repair. The patient underwent transabdominal embolization with coils and N-butyl cyanoacrylate/ethiodized oil (Lipiodol; Guerbet, Villepinte, France) mixture (2.5 mL). Because of the anticipated embolization artifacts on follow-up computed tomography (CT), technetium-99m-labeled human serum albumin diethylenetriamine pentaacetic acid single-photon emission computed tomography ((99m)Tc-HSAD SPECT) was performed before and after the intervention. Perigraft accumulation on (99m)Tc-HSAD SPECT corresponding to the endoleak disappeared after embolization. CT scan performed 12 months after embolization showed no signs of sac expansion. (99m)Tc-HSAD SPECT may be useful for evaluating therapeutic effect after embolization for endoleak. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Preclinical evaluation of a new, stabilized neurotensin(8--13) pseudopeptide radiolabeled with (99m)tc.

PubMed

García-Garayoa, Elisa; Bläuenstein, Peter; Bruehlmeier, Matthias; Blanc, Alain; Iterbeke, Koen; Conrath, Peter; Tourwé, Dirk; Schubiger, P August

2002-03-01

The rapid degradation of neurotensin (NT) limits its clinical use in cancer imaging and therapy. Thus, a new NT(8--13) pseudopeptide, NT-VIII, was synthesized. Some changes were introduced in the sequence of NT(8--13) to stabilize the molecule against enzymatic degradation: Arg(8) was N-methylated, and Lys and Tle replaced Arg(9) and Ile(12), respectively. Finally, (NalphaHis)Ac was coupled to the N-terminus for (99m)Tc(CO)(3) labeling. This peptide was characterized both in vitro and in vivo. The new analog was labeled with (99m)Tc(CO)(3). Its metabolic stability was analyzed both in human plasma and in HT-29 cells. Binding properties, receptor downregulation, and internalization were tested with HT-29 cells. Biodistribution was evaluated in nude mice with HT-29 xenografts. (99m)Tc(CO)(3)NT-VIII showed a high stability in plasma, where most of the peptide remained intact after 24 h of incubation at 37 degreesC. However, the degradation in HT-29 cells was more rapid (46% of intact (99m)Tc(CO)(3)NT-VIII after 24 h at 37 degreesC). Binding to NT1 receptors (NTR1) was saturable and specific. Scatchard analysis showed a high affinity for (99m)Tc(CO)(3)NT-VIII, with a dissociation constant similar to (125)I-NT (1.8 vs. 1.6 nmol/L). After interacting with NTR1, (99m)Tc(CO)(3)NT-VIII was rapidly internalized, with more than 90% internalized after 30 min. It also distributed and cleared rapidly in nude mice bearing HT-29 xenografts. The highest rates of accumulation were found in kidney and tumor at all time points tested. Tumor uptake was highly specific because it could be blocked by coinjection with a high dose of (NalphaHis)Ac-NT(8--13). Tumors were clearly visualized in scintigraphy images. The changes that were introduced stabilized the molecule against enzymatic degradation without affecting binding properties. Moreover, the increase in stability enhanced tumor uptake, making this derivative a promising candidate for clinical use.

Adsorption of 99mTc-sestamibi onto plastic syringes: evaluation of factors affecting the degree of adsorption and their impact on clinical studies.

PubMed

Swanson, Tiffinee N; Troung, Duong T; Paulsen, Andrew; Hruska, Carrie B; O'Connor, Michael K

2013-12-01

The purpose of this study was to document the extent of adhesion of (99m)Tc-sestamibi to syringes in patient procedures, determine factors that influence the degree of adhesion, and evaluate alternatives to our current practice that would either result in a more reproducible degree of adhesion or, ideally, eliminate adhesion. The extent of adhesion was documented in 216 patient procedures and evaluated in detail in an additional 73 patient procedures. We evaluated the nature of the adhesion and its possible causes, including the location of adhesion in injection sets, the effect of syringe type, and the effect of prerinsing of syringes with various solutions of nonradiolabeled sestamibi and (99m)Tc-sestamibi. The extent of adhesion was reevaluated in 50 procedures performed using the syringe type that demonstrated the lowest adhesion rate. The degree of adhesion of (99m)Tc-sestamibi to the injection set was found to be 20.1% ± 8.0%, with a range (10th-90th percentiles) of 9%-31%. The primary cause of adhesion appeared to be the lubricant used inside the syringe barrel. Evaluation of 6 different syringe types identified a brand with a lower adhesion rate. Reevaluation in patient procedures using this brand showed a 5.2% ± 2.5% degree of adhesion, with a range (10th-90th percentiles) of 2.5%-7.7%. Selection of the appropriate type of syringe can significantly reduce the magnitude and variability of residual (99m)Tc-sestamibi activity. With more reproducible residual activities, we have been able to achieve an approximately 20% reduction in the dispensed dose of (99m)Tc-sestamibi used in clinical procedures and a more consistent injected dose with less interpatient variation. The frequent changes in syringe design by manufacturers require that a quality control program for monitoring of residual activity be incorporated into clinical practice. This program has allowed us to maintain image quality and achieve more consistent injected patient doses in clinical procedures that use (99m)Tc-sestamibi.

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

PubMed

Ko, Toshiyuki; Utanohara, Yuko; Suzuki, Yasuhiro; Kurihara, Makiko; Iguchi, Nobuo; Umemura, Jun; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

2016-01-01

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.

The study of interaction of modified fatty acid with {sup 99m}Tc in alcoholic media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skuridin, V. S.; Stasyuk, E. S.; Varlamova, N. V.

2016-08-02

The paper presents the results of laboratory research aimed at the development of methods of synthesis of new radiodiagnostic agents based on modified fatty acid labelled with technetium-99m intended for scintigraphic evaluation of myocardial metabolism. In particular, the interaction of substance with {sup 99m}Tc in alcoholic media and the use of ethanol as solvent in the synthesis of the radiopharmaceutical were studied.

Significance of Technetium-99m Human Serum Albumin Diethylenetriamine Pentaacetic Acid Scintigraphy in Patients with Nephrotic Syndrome

PubMed Central

Takashima, Tsuyoshi; Kishi, Tomoya; Onozawa, Koji; Rikitake, Shuichi; Miyazono, Motoaki; Otsuka, Takateru; Irie, Hiroyuki; Iwakiri, Ryuichi; Fujimoto, Kazuma; Ikeda, Yuji

2015-01-01

It is thought that a large amount of albumin leaking from the glomerulus in nephrotic syndrome (NS) is reabsorbed at the proximal tubule and catabolized. Therefore, it is possible the final quantity of urinary protein does not always reflect the amount of leakage of protein from the glomerulus. We experienced two cases without nephrotic range proteinuria thought to involve hypoproteinemia due to the same pathophysiology as NS. On these patients, we performed protein leakage scintigraphy with technetium-99m human serum albumin diethylenetriamine pentaacetic acid (99mTc-HSAD) to exclude a diagnosis of protein-losing gastroenteropathy and observed diffuse positive accumulation in the kidneys with more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration. In healthy adults intravenously given 99mTc-HSAD, the same dynamics are observed as in albumin metabolism, and the organ radioactivity of the liver and kidneys after 24 hours is equal. Therefore, we thought it was possible that the renal uptake 24 hours after 99mTc-HSAD administration was a characteristic finding of NS. In order to confirm it, the subjects were divided into two groups: the NS group (n = 10) and the non-NS group (n = 7). We defined more intense uptake in the kidney than the liver on the anterior view 24 hours after 99mTc-HSAD administration as Dense Kidney (+). Furthermore, we designed regions of interest in the right and left kidneys and liver on anterior and posterior images, then calculated the kidney-liver ratio. Nine of the ten patients had Dense Kidney (+) in the NS group, compared to none in the non-NS group. And the kidney-liver ratio was significantly higher in the NS group than in the non-NS group on each view in the bilateral kidneys. In conclusion, our results suggest that the renal uptake 24 hours after 99mTc-HSAD administration is a characteristic finding of NS. PMID:25859658

Review of Extraskeletal Activity on Tc-99m Methylene Diphosphonate Bone Scintigraphy and Value of Cross-Sectional and SPECT-CT Imaging Correlation.

PubMed

Bermo, Mohammed; Behnia, Sanaz; Fair, Joanna; Miyaoka, Robert S; Elojeimy, Saeed

2017-07-31

Recognizing the different mechanisms and imaging appearance of extraskeletal Tc-99m methylene diphosphonate uptake enhances the diagnostic value of bone scan interpretation. In this article, we present a pictorial review of the different mechanisms of extraskeletal Tc-99m methylene diphosphonate uptake on bone scintigraphy including neoplastic, inflammatory, ischemic, traumatic, excretory, and iatrogenic. We also illustrate through case examples the added value of correlation with cross-sectional and single photon emission computed tomography and computed tomography imaging in localizing and characterizing challenging cases of extraskeletal uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.

PubMed

Ortiz, Jose Luis; Ortiz, Amparo; Milara, Javier; Armengot, Miguel; Sanz, Celia; Compañ, Desamparados; Morcillo, Esteban; Cortijo, Julio

2016-01-01

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.

Detection of gastritis by /sup 99m/Tc-labeled red-blood-cell scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilton, G.P.; Wahl, R.L.; Juni, J.E.

1984-10-01

Gastritis is a common condition, with a variety of causes, that is diagnosed most often by barium upper gastrointestinal tract series or endoscopy. The authors report a case in which gastritis without active bleeding was apparent in scintiscans obtained during the evaluation of GI bleeding using /sup 99m/Tc-labeled red blood cells (TcRBC). The scintigraphic findings that suggest gastritis are described.

Preclinical characterization of 18F-MAA, a novel PET surrogate of 99mTc-MAA.

PubMed

Wu, Shih-Yen; Kuo, Jia-Wei; Chang, Tien-Kuei; Liu, Ren-Shen; Lee, Rheun-Chuan; Wang, Shyh-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

2012-10-01

(99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy scan is routinely performed for lung perfusion imaging and for the assessment of in vivo distribution of (90)Y-labeled SIR-Spheres prior to selective internal radiation treatment for hepatocellular carcinoma. Positron emission tomography (PET) imaging is superior to gamma scintigraphy in terms of sensitivity, spatial resolution and accuracy of quantification. This study reported that (18)F-labeled macroaggregated albumin ((18)F-MAA) is an ideal PET imaging surrogate for (99m)Tc-MAA. (18)F-MAA was prepared from the commercial MAA kit via a one-step conjugation with N-succinimidyl 4-(18)F-fluorobenzoate ((18)F-SFB). The biodistribution study and microPET/microSPECT imaging were conducted in normal SD rats after intravenous injection of (18)F-MAA/(99m)Tc-MAA. A comparison study of these two radiotracers was performed after co-injection via the intrahepatic arterial in a N1S1 hepatoma-bearing SD rat model. The optimal condition for (18)F-MAA preparation is coupling MAA (0.5mg) with (18)F-SFB at 45°C for 5 min in a phosphate buffer of pH 8.5. (18)F-MAA was prepared in 60 min with high radiochemical yield (30%-35%) and high radiochemical purity (>95%). The in vivo distribution of (18)F-MAA after intravenous injection meets the specifications of MAA depicted in European Pharmacopeia. Our study demonstrated excellent correlation between (18)F-MAA and (99m)Tc-MAA in the regional distribution of tumor, liver and lungs (R(2)=0.965, 0.886 and 0.991, respectively), and also in the tumor-to-liver and tumor-to-lungs ratio (R(2)=0.965 and 0.987, respectively) in a N1S1 hepatoma-bearing SD rat model. The organ uptakes derived from animal PET/CT and SPECT/CT imaging after administration of these two tracers were in accordance with those obtained in the distribution studies. Starting from commercial MAA kit, an efficient preparation of (18)F-MAA was successfully established. Highly correlated, almost parallel, regional distribution of (18)F-MAA and (99m)Tc-MAA in both normal rats and hepatoma-bearing rats was observed. The findings, taken together, demonstrate that (18)F-MAA is an ideal surrogate for (99m)Tc-MAA for clinical PET applications. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.

PubMed

Runge, Roswitha; Oehme, Liane; Kotzerke, Jörg; Freudenberg, Robert

2016-12-01

DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO). Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay. Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively. For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.

Preparation and Identification of HER2 Radioactive Ligands and Imaging Study of Breast Cancer-Bearing Nude Mice.

PubMed

Zhang, Meng-Zhi; Guan, Yan-Xing; Zhong, Jin-Xiu; Chen, Xue-Zhong

2017-08-01

A micro-molecule peptide TP1623 of 99m Tc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated. TP1623 was chemically synthesized and labeled with 99m Tc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of 99m TC-TP1623 in normal mice was detected. SKBR3/MDA-MB-231-bearing nude mice models with high/low expressions of HER2 were established. Tumor tissues were stained with hematoxylin-eosin (HE) and measured by immunohistochemistry to confirm the formation of tumors and HER2 expression. SPECT imaging was conducted for HER2-overexpressing SKBR3-bearing nude mice. The T/NT ratio was calculated and compared with that of MDA-MB-231-bearing nude mice with low HER2 expression. The competitive inhibition image was used to discuss the specific binding of 99m Tc- TP1623 and the tumor. The labeling ratio of 99m Tc-TP1623, specific activity, and radiochemical purity (RCP) after 6 h at room temperature were (97.39 ± 0.23)%, (24.61 ± 0.06) TBq/mmol, and (93.25 ± 0.06)%, respectively. HER2 of SKBR3 and MDA-MB-231 cells showed high and low expression levels by immunohistochemistry, respectively. The in vitro receptor assays indicated that specific binding of TP1623 and HER2 was retained. Radioactivity in the brain was always at the lowest level, while the clearance rate of blood and the excretion rate of the kidneys were fast. HE staining showed that tumor cells were observed in SKBR3- and MDA-MB-231-bearing nude mice, with significant heteromorphism and increased mitotic count. The imaging of mice showed that targeted images could be made of 99m Tc-TP1623 in high HER2-expressing tumors, while no obvious development was shown in tumors in low HER2-expressing nude mice. No development was visible in tumors in competitive inhibition of imaging, which indicates the combination of 99m Tc-TP1623 and tumor was mediated by HER2. High labeling ratio and specific activity of 99m Tc-TP1623 is successfully prepared; it is a molecular imaging agent for HER2-positive tumors that has potential applicative value. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

[⁹⁹mTc]O₂-AMD3100 as a SPECT tracer for CXCR4 receptor imaging.

PubMed

Hartimath, Siddesh V; Domanska, Urszula M; Walenkamp, Annemiek M E; Rudi A J O, Dierckx; de Vries, Erik F J

2013-05-01

CXCR4 plays an important role in HIV infection, tumor progression, neurogenesis, and inflammation. In-vivo imaging of CXCR4 could provide more insight in the role of this receptor in health and disease. The aim of this study was to investigate [(99m)Tc]O₂-AMD3100 as a potential SPECT tracer for imaging of CXCR4. AMD3100 was labelled with [(99m)Tc]pertechnetate. A cysteine challenge assay was performed to test the tracer stability. Heterologous and homologous receptor binding assay and internalization assay were performed in CXCR4 expressing Jurkat-T cells. Ex vivo biodistribution was studied in healthy mice at 30, 60, and 120 min after tracer injection. Tumor uptake of the tracer was determined by microSPECT imaging in nude mice xenografted with human PC-3 prostate tumor. Specificity of tracer uptake was determined by blocking studies using an excess of unlabelled AMD3100. AMD3100 was labelled with technetium-99m with a radiochemical yield of >98%. The tracer was stable in PBS and mouse plasma for at least 6h at 37 °C. Heterologous and homologous binding assays with AMD3100 showed IC50 values of 240 ± 10 μM, and 92 ± 5 μM for [(125)I]SDF-1α and [(99m)Tc]O₂-AMD3100 respectively, with negligible receptor internalisation. The tracer showed high uptake in liver, lungs, spleen, thymus, intestine and bone. Blocking dose of AMD3100.8HCl (20mg/kg) decreased the uptake in these organs (p<0.05). [(99m)Tc]O2-AMD3100 showed specific tumor accumulation in mice bearing PC-3 xenografts model. Time activity curves (TAC) in AMD3100 pre-treated animals tracer showed 1.7 times less tumor uptake as compared to control animals (p<0.05). [(99m)Tc]O2-AMD3100 is readily labelled, is stable in plasma and displays a favourable binding affinity for the CXCR4 receptors. [(99m)Tc O₂-AMD3100 shows specific binding in organs with high CXCR4 expression and in CXCR4 positive tumors. These results justify further evaluation of this radiopharmaceutical as a potential biomarker for the non-invasive imaging of CXCR4 receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry.

PubMed

Bilton, Holly A; Ahmad, Zainab; Janzen, Nancy; Czorny, Shannon; Valliant, John F

2017-02-04

Pre-targeting combined with bioorthogonal chemistry is emerging as an effective way to create new radiopharmaceuticals. Of the methods available, the inverse electron demand Diels-Alder (IEDDA) cycloaddition between a radiolabeled tetrazines and trans-cyclooctene (TCO) linked to a biomolecule has proven to be a highly effective bioorthogonal approach to imaging specific biological targets. Despite the fact that technetium-99m remains the most widely used isotope in diagnostic nuclear medicine, there is a scarcity of methods for preparing 99m Tc-labeled tetrazines. Herein we report the preparation of a family of tridentate-chelate-tetrazine derivatives and their Tc(I) complexes. These hitherto unknown compounds were radiolabeled with 99m Tc using a microwave-assisted method in 31% to 83% radiochemical yield. The products are stable in saline and PBS and react rapidly with TCO derivatives in vitro. Their in vivo pre-targeting abilities were demonstrated using a TCO-bisphosphonate (TCO-BP) derivative that localizes to regions of active bone metabolism or injury. In murine studies, the 99m Tc-tetrazines showed high activity concentrations in knees and shoulder joints, which was not observed when experiments were performed in the absence of TCO-BP. The overall uptake in non-target organs and pharmacokinetics varied greatly depending on the nature of the linker and polarity of the chelate.

Exploring the Potential of (99m)Tc(CO)3-Labeled Triazolyl Peptides for Tumor Diagnosis.

PubMed

Gaonkar, Raghuvir H; Ganguly, Soumya; Baishya, Rinku; Dewanjee, Saikat; Sinha, Samarendu; Gupta, Amit; Ganguly, Shantanu; Debnath, Mita C

2016-04-01

In recent years the authors have reported on (99m)Tc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [(99m)Tc(CO)3(H2O)3](+) metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The (99m)Tc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using (99m)Tc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides.

Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging.

PubMed

Liu, Chang; Guo, Zhide; Zhang, Pu; Song, Manli; Zhao, Zuoquan; Wu, Xiaowei; Zhang, Xianzhong

2014-08-01

Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with (99m)Tc by formulated kit for SPECT imaging of hepatic function. p(VLA-co-VNI)(46:54) was synthesized by free-radical copolymerization initiated by AIBN, purified by dialysis, lyophilized to kit with Tricine and TPPTS as co-ligands for (99m)Tc labeling. Radiotracer (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was prepared and evaluated by in vitro stability, in vivo metabolism, ex vivo biodistribution and microSPECT/CT imaging in normal KM mice. MicroSPECT/CT and microMRI imaging were also performed in C57BL/b6 mice with xenograft hepatic carcinoma for hepatic function evaluation. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was obtained in high radio chemical purity (RCP) (>99%) by using instant kit without further purification and excellent in vitro and in vivo stability. The result of biodistribution showed that liver had high uptake (90.49±10.68 ID%/g) at 30 min after injection and was blocked significantly by cold copolymer. MicroSPECT imaging in normal KM mice at 1h and 4h after injection showed good liver retention and targeting properties. Significant defect of activity was observed in the tumor site which was confirmed by MRI imaging. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) with lower ratio of targeting moiety has no observable effect on the specific binding affinity and liver uptake. This makes it possible to introduce more imaging units for multi-modality imaging. Furthermore, the instant kit preparation of (99m)Tc-labeling provides great potential for the evaluation of hepatocyte function in clinical application. Copyright © 2014 Elsevier Inc. All rights reserved.

The value of 99mTc-MAA SPECT/CT for lung shunt estimation in 90Y radioembolization: a phantom and patient study.

PubMed

Allred, Jonathan D; Niedbala, Jeremy; Mikell, Justin K; Owen, Dawn; Frey, Kirk A; Dewaraja, Yuni K

2018-06-15

A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of 90 Y microspheres. Currently, 99m Tc macroaggregated albumin ( 99m Tc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from 99m Tc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from 99m Tc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared. A liver/lung torso phantom filled with 99m Tc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with 90 Y PET/CT-based measurements. In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between 99m Tc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3-29.4) for planar imaging and 3.2 Gy (range 0.4-13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from 90 Y PET/CT was 1.0%, (range 0.3-2.8). This value was not significantly different from the mean LSF estimate from 99m Tc-MAA SPECT/CT (mean 1.0%, range 0.4-1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2-15.0; p = 0.0002). The improved accuracy demonstrated by the phantom study, agreement with 90 Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that 99m Tc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.

A preliminary study of imaging paclitaxel-induced tumor apoptosis with (99)Tc(m)-His10-Annexin V.

PubMed

Zheng, Yu-min; Wang, Feng; Fang, Wei; Hua, Zi-chun; Wang, Zi-zheng; Meng, Qing-le; Yan, Jue

2013-01-01

In tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model. (99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity. (99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01). This study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

A sensitive and rapid radiolabelling method for the in vivo pharmacokinetic study of lentinan.

PubMed

Zhang, Yu; Zheng, Ziming; Yang, Xiawen; Pan, Xianglin; Yin, Lianglan; Huang, Xiao; Li, Qiang; Shu, Yamin; Zhang, Qilin; Wang, Kaiping

2018-06-20

The aim of this study is to establish a rapid and sensitive method for detecting lentinan (LNT) in biosamples and to evaluate the pharmacokinetics of LNT in mice and rats. A diethylenetriaminepentaacetic acid (DTPA) derivative of LNT (DTPA-LNT) was synthesized first to allow labelling with 99m-technetium (99mTc). After purification and identification, 99mTc-DTPA-LNT was intravenously administered to mice (2 mg kg-1) and rats at different doses (0.5, 2 and 8 mg kg-1). The results showed that the 99mTc-labelling method was suitable for the quantification of the LNT concentration in biological samples, with satisfactory linearity (r2 > 0.998), precision (<7%), accuracy (95.01-104.51%) and total recovery (∼90%). The blood concentration-time profiles of 99mTc-DTPA-LNT were consistent with the two-compartment model and showed a rapid distribution phase and a slow elimination, and no significant difference in the blood level of LNT was found among the tested doses (0.5, 2 and 8 mg kg-1). LNT was predominantly incorporated into the liver and spleen, and there was a small amount of aggregation in the bile, kidneys, lungs and stomach. Approximately 40% of the administered radioactivity was detected in urine and faeces within 24 h post-dosing. In addition, SPECT imaging of 99mTc-DTPA-LNT was performed to visually reveal the pharmacokinetic characteristics of LNT. These findings provide a reference for further study and for use of LNT and other β-glucans.

Unusual scintigraphic appearances of a mobile accessory lobe of the liver. [/sup 67/Ga; /sup 99m/Tc-sulfur colloid; /sup 99m/Tc-dihydrothioctic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bingham, J.B.; Maisey, M.N.

1978-11-01

Accessory hepatic lobules are an uncommon occurrence. In a gallium scan, a highly mobile, asymptomatic liver lobule gave rise to diagnostic confusion. It was resolved by the use of multiple radiopharmaceuticals.

18F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with 99mTc-MIBI or 99mTc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients.

PubMed

Beheshti, Mohsen; Hehenwarter, Lukas; Paymani, Zeinab; Rendl, Gundula; Imamovic, Larisa; Rettenbacher, Rupert; Tsybrovskyy, Oleksiy; Langsteger, Werner; Pirich, Christian

2018-03-08

In this prospective study we compared the accuracy of 18 F-fluorocholine PET/CT with that of 99m Tc-MIBI or 99m Tc-tetrofosmin SPECT/CT in the preoperative detection of parathyroid adenoma in patients with primary hyperparathyroidism. We also assessed the value of semiquantitative parameters in differentiating between parathyroid hyperplasia and adenoma. Both 18 F-fluorocholine PET/CT and 99m Tc-MIBI/tetrofosmin SPECT/CT were performed in 100 consecutive patients with biochemical evidence of primary hyperparathyroidism. At least one abnormal focus on either 18 F-fluorocholine or 99m Tc-MIBI/tetrofosmin corresponding to a parathyroid gland or ectopic parathyroid tissue was considered as a positive finding. In 76 patients with positive findings on at least one imaging modality, surgical exploration was performed within 6 months, and the results were related to histopathological findings and clinical and laboratory findings at 3-6 months as the standard of truth. In 24 patients, no surgery was performed: in 18 patients with positive imaging findings surgery was refused or considered risky, and in 6 patients imaging was negative. Therefore, data from 82 patients (76 undergoing surgery, 6 without surgery) in whom the standard of truth criteria were met, were used in the final analysis. All patients showed biochemical evidence of primary hyperparathyroidism with a mean serum calcium level of 2.78 ± 0.34 mmol/l and parathormone (PTH) level of 196.5 ± 236.4 pg/ml. The study results in 76 patients with verified histopathology and 3 patients with negative imaging findings were analysed. Three of six patients with negative imaging showed normalized serum PTH and calcium levels on laboratory follow-up at 3 and 6 months, and the results were considered true negative. In a patient-based analysis, the detection rate with 18 F-fluorocholine PET/CT was 93% (76/82), but was only 61% (50/82) with 99m Tc-MIBI/tetrofosmin SPECT/CT. In a lesion-based analysis, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of 18 F-fluorocholine PET/CT in the detection of parathyroid adenoma were 93.7%, 96.0%, 90.2%, 97.4% and 95.3%, respectively, and of 99m Tc-MIBI/tetrofosmin SPECT/CT were 60.8%, 98.5%, 94.1%, 86.3% and 87.7%, respectively. Although 18 F-fluorocholine PET-positive adenomatous lesions showed higher SUVmax values than the hyperplastic glands (6.80 ± 3.78 vs. 4.53 ± 0.40) in the semiquantitative analysis, the difference was not significant (p = 0.236). The mean size (measured as the length of the greatest dimension) and weight of adenomas were 15.9 ± 7.6 mm (median 15 mm, range 1-40 mm) and 1.71 ± 1.86 g (median 1 g, range: 0.25-9 g), respectively. Among the analysed parameters including serum calcium and PTH and the size and weight of parathyroid adenomas, size was significantly different between patients with negative 99m Tc-MIBI/tetrofosmin SPECT/CT and those with positive 99m Tc-MIBI/tetrofosmin SPECT/CT (mean size 13.4 ± 7.6 mm vs. 16.9 ± 7.4 mm, respectively; p = 0.042). In this prospective study, 18 F-fluorocholine PET/CT showed promise as a functional imaging modality, being clearly superior to 99m Tc-MIBI/tetrofosmin SPECT/CT, especially in the detection and localization of small parathyroid adenomas in patients with primary hyperparathyroidism. SUVmax was higher in parathyroid adenomas than in hyperplasia. However, further evaluation of this modality is needed.

99mTc Glucarate as a Potential Radiopharmaceutical Agent for Assessment of Tumor Viability: From Bench to the Bed Side

PubMed Central

Choudhury, Partha S.; Savio, E.; Solanki, K. K.; Alonso, O.; Gupta, A.; Gambini, J. P.; Doval, Dinesh; Sharma, P.; Dondi, M.

2012-01-01

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. 99mTc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with 18F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent 99mTc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent 99mTc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. 99mTc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy. PMID:23372437

Adsorption of (99m)Tc-radiopharmaceuticals onto injection vials and syringes.

PubMed

Mushtaq, Ahmad; Ur Rehman, Taj; Safdar Mansur, Muhammad; Jehangir, Mustanser

2008-06-01

Many groups have reported the adsorption or retention of (99m)Tc-radiopharmaceuticals on injection vials and disposable plastic syringes. Such an enormously high loss of radioactivity would result in poor images, radiation exposure, waste, and economic burdens. We therefore decided to investigate the extent of adsorption or retention of several (99m)Tc-radiopharmaceuticals on injection vials, rubber stoppers, and plastic syringes. These radiopharmaceuticals are produced as lyophilized kits in our department and supplied to various hospitals practicing nuclear medicine in Pakistan. A vial containing lyophilized material was reconstituted with 3 mL of freshly eluted Na(99m)TcO(4). A 1-mL aliquot of the resulting solution was withdrawn into a syringe at 0.25, 0.5, 1, 3, and 5 h after preparation. All preparations were stored at room temperature ( approximately 22 degrees C). After each withdrawal, the vial was reweighed and the activity remaining in the vial was measured using a radioisotope calibrator. The sample was reinjected into the vial. From the original weight and activity of solution in the vial, the initial activity per gram was calculated. From the weight and activity remaining in the vial after withdrawal of the sample, the activity per gram of the sample was calculated. From the difference between the initial activity per gram and the activity per gram of the sample, the percentage of (99m)Tc adsorbed on the vial was calculated. All preparations were kept in the syringe for 15 min, and the activity was measured before and after the syringe was emptied. The needle and plunger of the syringe were separated, and activity in the needle and plunger was also measured. The labeling efficiency of all radiopharmaceuticals used during these studies was more than 95%. In most cases, the activity of (99m)Tc found on the rubber stopper was less than 1%. Adsorption of (99m)Tc onto vials increased gradually with storage time. Adsorption was minimal at the initial stages, whereas maximum retention was noted after 5 h. Nearly 5% adsorption of activity was observed after 5 h of storage time on vials of sestamibi, mercaptoacetyltriglycine, dextran, ciprofloxacin, and dimercaptosuccinic acid (III and V). Retention of activity on needles ranged from 1% to 2% for all preparations studied. Plungers did not show any significant retention of radioactivity; in most cases, retention was less than 0.5%. The maximum retention of radioactivity on plastic syringe bodies was more than 3% for sestamibi, dimercaptosuccinic acid, dextran, pyrophosphate, and phytate. The results revealed that losses of radioactivity from (99m)Tc-radiopharmaceuticals in these objects (glass vial, rubber stopper, plastic syringes, plungers, and needles) are not alarming in our setup.

Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

PubMed

Okur, Neslihan Üstündağ; Özdemir, Derya İlem; Kahyaoğlu, Şennur Görgülü; Şenyiğit, Zeynep Ay; Aşıkoğlu, Makbule; Genç, Lütfi; Karasulu, H Yeşim

2015-01-01

The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.

Potential pitfalls in the nuclear medicine imaging: Experimental models to evaluate the effect of natural products on the radiolabeling of blood constituents, bioavailability of radiopharmaceutical and on the survival of Escherichia coli strains submitted to the treatment with stannous ion

NASA Astrophysics Data System (ADS)

Soares, Scheila F.; Brito, Lavínia C.; Souza, Deise E.; Bernardo, Luciana C.; Oliveira, Joelma F.; Bernardo-Filho, Mario

2006-12-01

Single photon emission computed tomography (SPECT) allows studies of physiological or pathological processes. Red blood cells labeled with technetium-99m ( 99mTc-RBC) are used as a radiopharmaceutical in several evaluations. The radiolabeling efficiency and bioavailability of radiopharmaceuticals can be altered by natural/synthetic drugs and may induce pitfalls in the analysis of the nuclear medicine imaging. The labeling with 99mTc requires a reducing agent and stannous chloride (SnCl 2) is widely utilized. However, SnCl 2 presents a citotoxic and/or genotoxic potential in Escherichia coli ( E. coli) strains. The aim of this work was to evaluate the influence of aqueous extracts of Baccharis genistelloides (BG), Terminalia chebula (TC), Maytenus ilicifolia (MI), Cassia angustifolia (CA) and Equisetum arvense (EA) on (i) radiolabeling of blood constituents, (ii) bioavailability of sodium pertechnetate(Na 99mTcO 4) radiopharmaceutical, (iii) survival of E. coli. In vitro labeling of RBC was performed with blood ( Wistar rats) incubated with each extract, SnCl 2 and Na 99mTcO 4. Plasma (P) and blood cells (BC) were isolated, another aliquots precipitated and soluble (SF) and insoluble (IF) fractions isolated and counted. In the bioavailability of Na 99mTcO 4, Wistar rats were treated (7 days) with aqueous extract or with 0.9%NaCl, the radiopharmaceutical was administered, the animals sacrificed, the organs isolated, weighted and radioactivity counted. To evaluate the effect on the bacterial survival, E. coli was treated with: (a) SnCl 2; (b) 0.9% NaCl; (c) vegetal extract; or (d) SnCl 2 and vegetal extract. Radiolabeling efficiency showed a significantly decrease (ANOVA/Tukey post-test, p<0.05) after treatment with BG, TC, MI and CA extracts. The bioavailability results showed that the uptake of Na 99mTcO 4 was altered significantly (unpaired t-student test, p<0.05) in blood, lungs (CA/TC extracts), bone, heart, ovary (EA /TC), spleen, kidney (TC) , pancreas, thyroid (CA) and liver (all the extracts). The alterations promoted by TC extract could be related to cardiotonic, antidiabetes and renal toxicity. The alteration in liver in EA and CA extracts could be related to its hepatoprotective activities. The extracts (EA, MI, BG) were not capable to interfere in the survival of E. coli. Moreover, these extracts have protected the E. coli against the SnCl 2 action and this fact can be related to the free radical scavenging properties of the chemical compounds of the extracts. In conclusion these findings could be worthwhile to try to understand and to avoid some pitfalls in the nuclear medicine.

Liquid scintillation counting methodology for 99Tc analysis. A remedy for radiopharmaceutical waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Mumtaz; Um, Wooyong

2015-08-13

This paper presents a new approach for liquid scintillation counting (LSC) analysis of single-radionuclide samples containing appreciable organic or inorganic quench. This work offers better analytical results than existing LSC methods for technetium-99 ( 99gTc) analysis with significant savings in analysis cost and time. The method was developed to quantify 99gTc in environmental liquid and urine samples using LSC. Method efficiency was measured in the presence of 1.9 to 11,900 ppm total dissolved solids. The quench curve was proved to be effective in the case of spiked 99gTc activity calculation for deionized water, tap water, groundwater, seawater, and urine samples.more » Counting efficiency was found to be 91.66% for Ultima Gold LLT (ULG-LLT) and Ultima Gold (ULG). Relative error in spiked 99gTc samples was ±3.98% in ULG and ULG-LLT cocktails. Minimum detectable activity was determined to be 25.3 mBq and 22.7 mBq for ULG-LLT and ULG cocktails, respectively. A pre-concentration factor of 1000 was achieved at 100°C for 100% chemical recovery.« less

Thyroid uptake of (/sup 99m/Tc) pertechnetate during in vivo RBC labeling: incidental diagnosis of hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, K.A.; Ponto, J.A.

1981-09-01

Increased thyroid activity was incidentally observed during an in vivo labeled Tc-99m blood pool scan and subsequent evaluation resulted in a diagnosis of hypothyroidism. Alternate explanations of abnormal thyroid uptake on in vivo labeled blood pool scans were considered and are discussed briefly.

Extravasation of contrast material from vascular ectasia of the cecum detected with /sup 99m/Tc-pertechnetate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tavormina, A.; Mousavi, A.; Gordon, D.H.

A case of vascular ectasia of the cecum is presented. The isotopic pattern did not differ from that of Meckel's diverticulum. The authors suggest that studies with /sup 99m/Tc may be helpful in screening for areas of pathology in cases of lower gastrointestinal bleeding.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quigley, Kevin; Chemerisov, Sergey; Tkac, Peter

Through irradiations using our 3 MeV Van de Graaf accelerator, Argonne is testing the radiation stability of components of equipment that are being used to dispense molybdenum solutions for use as feeds to 99mTc generators and in the 99mTc generators themselves. Components have been irradiated by both a direct electron beam and photons generated from a tungsten convertor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H.B.; Wexler, J.P.; Scharf, S.C.

The effect of two antihypertensive agents (captopril and prazosin) and of digoxin on the efficiency of Tc-99m binding to RBCs was evaluated in the rat. RBCs were labeled with Tc-99m in vivo in six groups of rats: I-normotensive controls Wistar rat (WR), II-prazosin treated WR, III-spontaneously hypertensive rat (SHR), IV-prazosin-treated SHR, V-digoxin-treated WR, and VI-captopril-treated WR. The percentage of intravascular Tc-99m bound to RBC (%T) and the percentage of injected dose remaining intravascular 5 min after injection (%i.v.) were determined. Mean %T was 94.2, 83.8, 94.9, 86.1, 79.7, and 93.3 for groups I-VI respectively. Mean %I.V. was 96.4, 74.6, 94.9,more » 79.0, 74.4, and 87.4 for groups I-VI respectively. The findings demonstrate a significant reduction of RBC tagging with Tc-99m in rats treated with prazosin and digoxin but not with captopril. The data suggest a potential interference by patient medication with the performance of blood-pool studies.« less

[Study of dopamine transporter imaging on the brain of children with autism].

PubMed

Sun, Xiaomian; Yue, Jing; Zheng, Chongxun

2008-04-01

This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.

In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

PubMed

Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

2013-05-01

Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shuang Liu

2012-10-24

This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition ofmore » G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.« less