Sample records for tc-99m sulfur colloid

  1. 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.

  2. 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.

  3. 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.

  4. Lung uptake of /sup 99m/Tc--sulfur colloid in falciparum malaria: case report

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

    Ziessman, H.A.

    Increased lung uptake of /sup 99m/Tc-sulfur colloid was seen during liver scanning in a patient with falciparum malaria. This finding was due to the enhanced activity of the phagocytic cells of the reticuloendothelial system in the liver, spleen, and lung found in human and experimental malaria. Similar findings in other clinical situations and the relevant literature are reviewed.

  5. 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

  6. 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.

  7. 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.

  8. Significance of /sup 99m/Tc-sulfur colloid splenic image in malignant melanoma

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

    Berjian, R.A.; Parthasarathy, K.L.; Didolkar, M.S.

    To evaluate the clinical significance of /sup 99m/Tc-sulfur-colloid (TcSC) spleen scan findings in patients with malignant melanoma, a retrospective study was undertaken. Eighty-one patients with histologically proven malignant melanoma who received treatment in Roswell Park during a five-year period were included in this study. The scans were analyzed for spleen size, differential uptake of the tracer in liver and spleen, and for the presence of metastases in these two organs. These data were compared with stage of disease, survival, and autopsy findings. Significant correlation was found between the splenic size as measured on the scintiscan and at autopsy examination. Themore » spleen size was found to be normal in 92% of the patients in early melanoma. The median survival of patients who had a normal-sized spleen by scan criteria was found to be longer than those who had splenomegaly. No significant difference in survival was noted between the patients with and without augmented splenic uptake of TcSC. Only a small number (17.7%) of patients with augmented splenic uptake had splenic metastases; hence, the possible role of immunological factors was considered.« less

  9. 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.

  10. 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

  11. Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy.

    PubMed

    Matesan, Manuela M; Bowen, Stephen R; Chapman, Tobias R; Miyaoka, Robert S; Velez, James W; Wanner, Michele F; Nyflot, Matthew J; Apisarnthanarax, Smith; Vesselle, Hubert J

    2017-07-01

    A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (Tc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected Tc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. Thirty patients with chronic liver disease and primary liver cancers underwent Tc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction Tc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned Tc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of Tc-SC biodistribution to liver function parameters and liver disease scoring systems (Child-Pugh) were evaluated by Spearman rank correlation. Percentages of Tc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman's correlation coefficient showed a significant statistical association between Child-Pugh score and bone marrow uptake at 0.55 (P≤0.05), liver uptake at 0.71 (P≤0

  12. In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

    PubMed

    Dar, Ume-Kalsoom; Khan, Irfanullah; Javed, Muhammad; Ali, Muhammad; Hyder, Syed Waqar; Murad, Sohail; Anwar, Jamil

    2013-03-01

    In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

  13. Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement

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

    Garty, I.; Tal, I.; Kaynan, A.

    1984-06-01

    Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

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

    Bowen, S; Miyaoka, R; Kinahan, P

    2014-06-15

    Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined bymore » liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with

  20. 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

  1. Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

    PubMed

    Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R; Chagpar, Anees B; Killelea, Brigid K; Lannin, Donald R

    2017-01-01

    Background . Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods . Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results . At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion . Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.

  2. Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience

    PubMed Central

    Berrocal, Julian; Saperstein, Lawrence; Grube, Baiba; Horowitz, Nina R.; Chagpar, Anees B.

    2017-01-01

    Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1–15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient. PMID:28492062

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. Scintigraphic scoring system for grading severity of gastro-esophageal reflux on 99mTc sulfur colloid gastro-esophageal reflux scintigraphy: A prospective study of 39 cases with pre and post treatment assessment.

    PubMed

    Puranik, Ameya D; Nair, Gopinathan; Aggarwal, Rajiv; Bandyopadhyay, Abhijit; Shinto, Ajit; Zade, Anand

    2013-04-01

    The study aimed at developing a scoring system for scintigraphic grading of gastro-esophageal reflux (GER), on gastro-esophageal reflux scintigraphy (GERS) and comparison of clinical and scintigraphic scores, pre- and post-treatment. A total of 39 cases with clinically symptomatic GER underwent 99mTc sulfur colloid GERS; scores were assigned based on the clinical and scintigraphic parameters. Post domperidone GERS was performed after completion of treatment. Follow up GERS was performed and clinical and scintigraphic parameters were compared with baseline parameters. Paired t-test on pre and post domperidone treatment clinical scores showed that the decline in post-treatment scores was highly significant, with P value < 0.001. The scintigraphic scoring system had a sensitivity of 93.9% in assessing treatment response to domperidone, specificity of 83.3% i.e., 83.3% of children with no decline in scintigraphic scores show no clinical response to Domperidone. The scintigraphic scoring system had a positive predictive value of 96.9% and a negative predictive value of 71.4%. GERS with its quantitative parameters is a good investigation for assessing the severity of reflux and also for following children post-treatment.

  14. [99mTc(V)-DMSA accumulation in gynecomastia].

    PubMed

    Ohta, H

    1998-11-01

    The accumulation of 99mTc(V)-DMSA in bilateral breasts was recognized in a 60-year-old male with drug-induced gynecomastia. There are some reports describing 99mTc(V)-DMSA accumulation in normal female breast, fibrous dysplasia of the breast and metastatic lesions of breast carcinoma, but to my knowledge, there have been no reports describing 99mTc(V)-DMSA accumulation in gynecomastia.

  15. 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.

  16. Tc-99m Ethylenedicysteine and Tc-99m Dimercaptosuccinic Acid Scintigraphy-Comparison of the Two for Detection of Scarring and Differential Cortical Function.

    PubMed

    Dharmalingam, Anitha; Pawar, Shwetal U; Parelkar, Sandesh V; Shetye, Suruchi S; Ghorpade, Mangala K; Tilve, Gundu H

    2017-01-01

    The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied. The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA. Prospective observational study of recurrent UTI; minimum 6 weeks after acute episode; when urine examination is negative for pus cells. Forty-seven children with normal positioned kidneys underwent Tc-99m EC and DMSA scintigraphy. The DRF and cortical phase images of both studies in the same image matrix size were evaluated by two independent observers for scarring; Tc-99m DMSA was considered as the gold standard. MS Excel 2007 and GraphPad Instat V3.1 and ROC analysis. There was no significant difference in the detection of scarring using two studies with Cohen's kappa coefficient (κ) 0.932. The sensitivity and specificity of Tc-99m EC for detection of scarring was 98.75% and 99.15%, respectively. There was good agreement between the differential cortical function calculated using two studies. The summed Tc-99m EC images with an acceptable high image contrast allow detection of cortical scarring in patients with normal kidney positions. It is an excellent single-modality comprehensive investigational agent for renal parenchymal defects, function, and excretion evaluation with the added advantages of lower cost, convenience, and low radiation exposure to the child.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Mannosylated dextran derivatives labeled with fac-[M(CO)₃]+ (M = (99m)Tc, Re) for specific targeting of sentinel lymph node.

    PubMed

    Morais, Maurício; Subramanian, Suresh; Pandey, Usha; Samuel, Grace; Venkatesh, Meera; Martins, Manuel; Pereira, Sérgio; Correia, João D G; Santos, Isabel

    2011-04-04

    Despite being widely used in the clinical setting for sentinel lymph node detection (SLND), (99m)Tc-based colloids (e.g., (99m)Tc-human serum albumin colloids) present a set of properties that are far from ideal. Aiming to design novel compounds with improved biological properties, we describe herein the first class of fully characterized (99m)Tc(CO)₃-mannosylated dextran derivatives with adequate features for SLND. Dextran derivatives, containing the same number of pendant mannose units (13) and a variable number (n) of tridentate chelators (9, n = 1; 10, n = 4, 11, n= 12), have been synthesized and fully characterized. Radiolabeled polymers of the type fac-[(99m)Tc(CO)₃(k³-L)] (12, L = 9, 13, L = 10, 14, L = 11) have been obtained quantitatively in high radiochemical purity (≥ 98%) upon reaction of the dextran derivatives with fac-[(99m)Tc(CO)₃(H₂O)₃]+. The highly stable compounds 13 and 14 were identified by comparing their HPLC chromatograms with the ones obtained for the corresponding rhenium surrogates fac-[Re(CO)₃(k³-10)] (13a) and fac-[Re(CO)₃(k³-11)] (14a), which have been characterized both at the chemical (NMR and IR spectroscopy, and HPLC) and physical level (DLS, AFM and LDV). Compounds 13a and 14a present a positive zeta potential (+ 7.1 mV, pH 7.4) and a hydrodynamic diameter in the range 8.4-8.7 nm. Scintigraphic imaging and biodistribution studies in Wistar rats have shown good accumulation in the sentinel node at 60 min postinjection (6.71 ± 2.35%, 13; and 7.53 ± 0.69%, 14), with significant retention up to 180 min. A clear delineation of the sentinel lymph node without significant washout to other regions was observed in the scintigraphic images. The popliteal extraction of 94.47 ± 2.45% for 14 at 1 h postinjection, as compared to 61.81 ± 2.4% for 13, indicated that 14 is a very promising compound to be further explored as SLN imaging agent.

  5. 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.

  6. 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.

  7. Simultaneous Tc-99m skeletal and In-111 hip arthrographic scintimaging complementing contrast radiography

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

    Wellman, H.N.; Uri, B.G.; Stiner, P.

    1984-01-01

    Prosthetic hip replacement has become a frequent procedure with femoral component (FC) loosening occurring frequently at a rate of 24% at 7 yrs post arthroplasty. Pain may occur from a variety of causes and identification of loosening as the cause is critical. Experience with radiographic contrast arthrography (XA) alone has often resulted in equivocal studies because of confusion caused by the radio-opaque glue-bone interface and adjacent radiolucency of the FC. Radionuclide arthrography (RA) with Tc-99m Sulfur Colloid (SC) has been previously shown to improve the efficiency of FC loosening determination. However, with extravasation or other confusing patterns of tracer distributionmore » more precise localization relative to skeletal structure is required with RA. Simultaneous use of RA using In-111 (IN) chloride (0.2 mCi) injected with contrast at XA superimposed on prior injected TC-99m MDP (20 mCi) skeletal imaging (SI) has considerably improved interpretation and complemented XA, correlated with surgery. Fifty RA and XA patients have been studied: 18 with SC alone, 7 with SC and IN in the joint space simultaneously and 25 with IN RA and SI. Simultaneous joint injection RA with IN and SC demonstrated exactly the same pattern with no translocation of IN. Thirty patients had surgery with 20 loose FC verified; all loose by RA but only 16 by XA plus 2 false positives. Also simultaneous SI has shown unreliable criteria for FC loosening. Thus, addition of simultaneous RA and SI for FC evaluation is a valuable adjunct in 20% of patients in the performance of arthrography.« less

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. (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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 99M-Technetium labeled tin colloid radiopharmaceuticals

    DOEpatents

    Winchell, Harry S.; Barak, Morton; Van Fleet, III, Parmer

    1976-07-06

    An improved 99m-technetium labeled tin(II) colloid, size-stabilized for reticuloendothelial organ imaging without the use of macromolecular stabilizers and a packaged tin base reagent and an improved method for making it are disclosed.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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).

  14. 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.

  15. 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.

  16. Technetium-99m NGA functional hepatic imaging: preliminary clinical experience

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

    Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

    1985-11-01

    Technetium-99m galactosyl-neoglycoalbumin ( (Tc)NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis, and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and (Tc)sulfur colloid scintigraphy. Kinetic modeling of dynamic (Tc)NGA data produced estimates of standardizedmore » hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, (HBP). Significant rank correlation was obtained between (HBP) estimates and CTC scores. This correlation supports the hypothesis that (HBP) is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced (HBP) may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.« less

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

    PubMed

    Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

    2004-04-01

    An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

  8. 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.

  9. [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.

  10. 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

  11. (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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Biokinetics and dosimetric studies about 99mTc(V)-DMSA distribution.

    PubMed

    Correia, M B L; Magnata, S S L P; Silva, I M S; Catanho, M T J A; Lima, F F

    2010-05-10

    Research for radiodiagnostic agents should considerate biological critical parameters which will give own contribution on the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with (99m)Tc(V) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in evaluation of bone metastasis. This work studied the biokinetics and dosimetry of (99m)Tc(V)-DMSA by animal model. The (99m)Tc(V)-DMSA was prepared from a (III)DMSA kit alkalized. Mice (n=5) received (99m)Tc(V)DMSA i.v., they were sacrificed (30 min, 1h, 5h and 12h), the organs excised and the activities measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated (MIRDOSE 3.0 program) by extrapolation of data from animal to human scale. The results showed the majority of organs reached the top uptake at 30 min, the greatest kidney uptake was (4.81 +/- 1.38)% activity/g, while the bone presented its highest uptake at 1h (5.49+/- 0.47)% activity/g, after 1h all the organs had activity exponential decrease. The biokinetic profile of (99m)Tc(V)-DMSA was well established, allowing quantifying of residence time, and the radiation dose estimates were made for this agent. About the absorbed dose, the preliminary results showed higher value to bone, being the soft tissue dose relatively low.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. (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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. [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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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%.

  14. 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.

  15. 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.

  16. .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.

  17. 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

  18. 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

  19. 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.

  20. Technetium-99m colloidal bismuth subcitrate: A novel method for the evaluation of peptic ulcer disease

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

    Vasquez, T.E.; Lyons, K.P.; Raiszadeh, M.

    1984-01-01

    The therapeutic agent colloidal bismuth subcitrate (CBS) selectively binds to peptic ulcers. The authors have developed a method for labeling this agent with Tc-99m. Chromatographic quality control studies of the agent on silica gel coated strips (ITLC-SG) showed that more than 97% of Tc-99m was bound to CBS. During in-vitro stability testing, the radio-label was stable for a minimum of 6 hours. The chromatographic findings are in agreement with the in-vivo distribution of the agent which showed no significant radioactivity in thyroid, kidneys, liver, or bladder. The resulting Tc-99m-CBS solution is administered orally in drinking water. Preliminary animal studies havemore » been conducted on 5 adult 3 kg New Zealand rabbits sedated with 50 mg Ketamine I.M. The rabbits were intubated with I.V. tubing advanced to the stomach. They were given a gastric erosive suspension of 600-1000 mg/kg of pulverized ASA in 10 cc tap water. Four hours later they were given 3-4 mCi of the radiotracer in a 5 cc volume of water. Serial in-vivo images were obtained for 2 hours which included thyroid, abdomen, and urinary bladder. Next the stomachs were excised, opened along the greater curvature, imaged, vigorously washed and reimaged. All 5 rabbits showed avid localized binding of radiotracer which remained fixed even with vigorous washing. Areas of normal appearing mucosa were relatively devoid of radiotracer. This new compound may have significant clinical usefulness in the detection of peptic ulcer disease. In addition, such a non-invasive technique, carrying none of the risks or discomfort of endoscopy could also find application in the evaluation of the response to therapy.« less

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. (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

  6. 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.

  7. 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

  8. 99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma

    PubMed Central

    Sowa-Staszczak, Anna; Trofimiuk-Müldner, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Buziak-Bereza, Monika; Gilis-Januszewska, Aleksandra; Jabrocka-Hybel, Agata; Głowa, Bogusław; Małecki, Maciej; Bednarczuk, Tomasz; Kamiński, Grzegorz; Kowalska, Aldona; Mikołajczak, Renata; Janota, Barbara; Hubalewska-Dydejczyk, Alicja

    2016-01-01

    Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. Imaging Thromboembolism with Fibrin-Avid 99mTc-Peptide: Evaluation in Swine

    PubMed Central

    Aruva, Mohan R.; Daviau, Judy; Sharma, Shubh S.; Thakur, Mathew L.

    2006-01-01

    A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for α-chain-fibrin was labeled with 99mTc (99mTc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). Methods Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. 99mTc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, 99mTc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. Results The affinity for human fibrin was 10−9 mol/L and there were >1015 receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9–22.6), DVT/muscle (31.1–89.4), PE/blood (1–155), and PE/lung (0.8–245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the γ-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. Conclusion 99mTc-TP850 with its modest affinity (10−9 mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis. PMID:16391200

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Sorption of99mTc radiopharmaceutical compounds by soils

    USGS Publications Warehouse

    Jurisson, S.; Gawenis, J.; Landa, E.R.

    2004-01-01

    Study of the sorption of 99mTc radiopharmaceutical compounds by soils has assessed the fate of these compounds in the event of a surface spill and examined the potential of these compounds as hydrologic tracers. Sorption from deionized water, filtered Missouri River water, and artificial seawater by five surface soils was investigated. For all water types, the Tc radiopharmaceutical compounds showed greater sorption than the uncomplexed pertechnetate. The most lipophilic complexes showed the highest sorption on soils.

  10. 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.

  11. 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

  12. [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.

  13. 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

  14. Determination of 99Tc in fresh water using TRU resin by ICP-MS.

    PubMed

    Guérin, Nicolas; Riopel, Remi; Kramer-Tremblay, Sheila; de Silva, Nimal; Cornett, Jack; Dai, Xiongxin

    2017-10-02

    Technetium-99 ( 99 Tc) determination at trace level by inductively coupled plasma mass spectrometry (ICP-MS) is challenging because there is no readily available appropriate Tc isotopic tracer. A new method using Re as a recovery tracer to determine 99 Tc in fresh water samples, which does not require any evaporation step, was developed. Tc(VII) and Re(VII) were pre-concentrated on a small anion exchange resin (AER) cartridge from one litre of water sample. They were then efficiently eluted from the AER using a potassium permanganate (KMnO 4 ) solution. After the reduction of KMnO 4 in 2 M sulfuric acid solution, the sample was passed through a small TRU resin cartridge. Tc(VII) and Re(VII) retained on the TRU resin were eluted using near boiling water, which can be directly used for the ICP-MS measurement. The results for method optimisation, validation and application were reported. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. /sup 99m/Tc-fibrinogen scanning in adult respiratory distress syndrome

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

    Quinn, D.A.; Carvalho, A.C.; Geller, E.

    1987-01-01

    Fibrin is often seen occluding the lung vessels of patients dying from ARDS and is surrounded by regions of lung necrosis. To learn if we could observe increased or focal fibrin deposition and assess the kinetics of plasma fibrinogen turnover during severe acute respiratory failure, we injected technetium 99m-labeled human purified fibrinogen (Tc-HF) and used gamma camera scanning for as long as 12 h in 13 sequential patients as soon as possible after ICU admission. The fibrinogen uptake rates were determined by calculating the lung:heart radioactivity ratios at each time point. Slopes of the lung:heart ratio versus time were comparedmore » between ARDS and mild acute respiratory failure (ARF). The slope of the lung:heart Tc-HF ratio of the 9 patients with ARDS (2.9 +/- 0.4 units) was markedly higher (p less than 0.02) than the slope of the 4 patients with mild ARF (1.1 +/- 0.4) and the 3 patients studied 5 to 9 months after recovery from respiratory failure (0.7 +/- 0.07). In the 1 patient with ARDS and the 2 patients with mild ARF studied both during acute lung injury and after recovery, the lung:heart Tc-HF ratio had decreased at recovery. To compare the pulmonary uptake of Tc-HF to /sup 99m/Tc-labeled human serum albumin (Tc-HSA), 5 patients were injected with 10 mCi of Tc-HSA, and scanning of the thorax was performed with a similar sequential imaging protocol 24 h after conclusion of the Tc-HF study.« less

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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).

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 99mTc: Labeling Chemistry and Labeled Compounds

    NASA Astrophysics Data System (ADS)

    Alberto, R.; Abram, U.

    This chapter reviews the radiopharmaceutical chemistry of technetium related to the synthesis of perfusion agents and to the labeling of receptor-binding biomolecules. To understand the limitations of technetium chemistry imposed by future application of the complexes in nuclear medicine, an introductory section analyzes the compulsory requirements to be considered when facing the incentive of introducing a novel radiopharmaceutical into the market. Requirements from chemistry, routine application, and market are discussed. In a subsequent section, commercially available 99mTc-based radiopharmaceuticals are treated. It covers the complexes in use for imaging the most important target organs such as heart, brain, or kidney. The commercially available radiopharmaceuticals fulfill the requirements outlined earlier and are discussed with this background. In a following section, the properties and perspectives of the different generations of radiopharmaceuticals are described in a general way, covering characteristics for perfusion agents and for receptor-specific molecules. Technetium chemistry for the synthesis of perfusion agents and the different labeling approaches for target-specific biomolecules are summarized. The review comprises a general introduction to the common approaches currently in use, employing the N x S4-x , [3+1] and 2-hydrazino-nicotinicacid (HYNIC) method as well as more recent strategies such as the carbonyl and the TcN approach. Direct labeling without the need of a bifunctional chelator is briefly reviewed as well. More particularly, recent developments in the labeling of concrete targeting molecules, the second generation of radiopharmaceuticals, is then discussed and prominent examples with antibodies/peptides, neuroreceptor targeting small molecules, myocardial imaging agents, vitamins, thymidine, and complexes relevant to multidrug resistance are given. In addition, a new approach toward peptide drug development is described. The section

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA

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

    Ohta, H.; Shane, F.I.; Endo, K.

    1986-12-01

    The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.

  15. 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.

  16. /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.

  17. 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

  18. 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

  19. Total-hip arthroplasty: Periprosthetic indium-111-labeled leukocyte activity and complementary technetium-99m-sulfur colloid imaging in suspected infection

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

    Palestro, C.J.; Kim, C.K.; Swyer, A.J.

    1990-12-01

    Indium-111-labeled leukocyte images of 92 cemented total-hip arthroplasties were correlated with final diagnoses. Prostheses were divided into four zones: head (including acetabulum), trochanter, shaft, and tip. The presence (or absence) and intensity of activity in each zone was noted, and compared to the corresponding contralateral zone. Though present in all 23 infected arthroplasties, periprosthetic activity was also present in 77% of uninfected arthroplasties, and was greater than the contralateral zone 51% of the time. When analyzed by zone, head zone activity was the best criterion for infection (87% sensitivity, 94% specificity, 92% accuracy). Fifty of the arthroplasties were studied withmore » combined labeled leukocyte/sulfur colloid imaging. Using incongruence of images as the criterion for infection, the sensitivity, specificity, and accuracy of the study were 100%, 97%, and 98%, respectively. While variable periprosthetic activity makes labeled leukocyte imaging alone unreliable for diagnosing hip arthroplasty infection, the addition of sulfur colloid imaging results in a highly accurate diagnostic procedure.« less

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Effects of 99mTc-TRODAT-1 drug template on image quantitative analysis

    PubMed Central

    Yang, Bang-Hung; Chou, Yuan-Hwa; Wang, Shyh-Jen; Chen, Jyh-Cheng

    2018-01-01

    99mTc-TRODAT-1 is a type of drug that can bind to dopamine transporters in living organisms and is often used in SPCT imaging for observation of changes in the activity uptake of dopamine in the striatum. Therefore, it is currently widely used in studies on clinical diagnosis of Parkinson’s disease (PD) and movement-related disorders. In conventional 99mTc-TRODAT-1 SPECT image evaluation, visual inspection or manual selection of ROI for semiquantitative analysis is mainly used to observe and evaluate the degree of striatal defects. However, these methods are dependent on the subjective opinions of observers, which lead to human errors, have shortcomings such as long duration, increased effort, and have low reproducibility. To solve this problem, this study aimed to establish an automatic semiquantitative analytical method for 99mTc-TRODAT-1. This method combines three drug templates (one built-in SPECT template in SPM software and two self-generated MRI-based and HMPAO-based TRODAT-1 templates) for the semiquantitative analysis of the striatal phantom and clinical images. At the same time, the results of automatic analysis of the three templates were compared with results from a conventional manual analysis for examining the feasibility of automatic analysis and the effects of drug templates on automatic semiquantitative analysis results. After comparison, it was found that the MRI-based TRODAT-1 template generated from MRI images is the most suitable template for 99mTc-TRODAT-1 automatic semiquantitative analysis. PMID:29543874

  6. 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

  7. 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.

  8. [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.

  9. [(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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. Normal regional distribution of cerebral blood flow in dogs: comparison between (99m) Tc-ethylcysteinate dimer and (99m) Tc- hexamethylpropylene amine oxime single photon emission computed tomography.

    PubMed

    Adriaens, Antita; Polis, Ingeborgh; Waelbers, Tim; Vandermeulen, Eva; Dobbeleir, André; De Spiegeleer, Bart; Peremans, Kathelijne

    2013-01-01

    Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable. © 2013 Veterinary Radiology & Ultrasound.

  15. 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.

  16. Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc.

    PubMed

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

    2016-12-07

    Cyclotron-produced 99m Tc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99m Tc. However, the small amount of 92-98 Mo in the irradiation of enriched 100 Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

  17. Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

    Cyclotron-produced 99mTc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99mTc. However, the small amount of 92-98Mo in the irradiation of enriched 100Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

  18. 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

  19. (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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Preclinical Evaluation of 68Ga-MAA from Commercial Available 99mTc-MAA Kit

    PubMed Central

    Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Lahooti, Afsaneh; Geramifar, Parham; Beiki, Davood; Yousefnia, Hassan; Rabiee, Amir; Mazidi, Mohammad; Mirshojaei, Seyedeh Fatemeh; Maus, Stephan

    2017-01-01

    99mTc-Macroaggregated Albumin (99mTc-MAA) has been used as a perfusion agent. This study described development of the 68Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99mTc-MAA kit. 68Ge/68Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68GaCl3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99mTc-MAA remained longer than 68Ga-MAA in the lung and 68Ga-MAA showed better image qualities, using 68Ga-MAA is recommended. PMID:29552050

  8. Preclinical Evaluation of 68Ga-MAA from Commercial Available 99mTc-MAA Kit.

    PubMed

    Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Lahooti, Afsaneh; Geramifar, Parham; Beiki, Davood; Yousefnia, Hassan; Rabiee, Amir; Mazidi, Mohammad; Mirshojaei, Seyedeh Fatemeh; Maus, Stephan

    2017-01-01

    99m Tc-Macroaggregated Albumin ( 99m Tc-MAA) has been used as a perfusion agent. This study described development of the 68 Ga-MAA via commercially available kits from Pars-Isotopes Company as a 99m Tc-MAA kit. 68 Ge/ 68 Ga generator was eluted with suprapure HCl (0.6 M, 6 mL) in 0.5 mL fractions. The two fractions with the highest 68 GaCl 3 activity were generally used for labeling purposes. After labeling, the final product was centrifuged 2 times to purify the solution. Five rats were sacrificed at each exact time interval (from 15 min to 2 h post injection) and the percentage of injected dose per gram (%ID/g) of each organ was measured by direct counting from 11 harvested organs of rats. The RTLC showed that labeling yields before centrifuges were 90% and 95% for Pars-Isotopes and GE kits, respectively and after centrifuges, they became 100%. The microscopic size examination showed a shift in the particle sizes post centrifuges and the biodistribution data revealed the efficiency and benefits of centrifuges in terms of preventing the of liver and bone marrow uptakes especially for Pars-Isotopes kits. Our results showed that after centrifuges of the final product, the lung uptakes increased from 89% to more than 97% of %ID/g after 5 min post injections. The whole procedure took less than 25 min from elution to the final product. Since 99m Tc-MAA remained longer than 68 Ga-MAA in the lung and 68 Ga-MAA showed better image qualities, using 68 Ga-MAA is recommended.

  9. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

    da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  10. Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

    Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

    1981-04-01

    Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy.

    PubMed

    Rachinsky, I; Boguslavsky, L; Goldstein, D; Golan, H; Pak, I; Katz, M; Lantsberg, S

    2000-12-01

    Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent 99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with 99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of 99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.

  20. 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.

  1. Spatially resolved assessment of hepatic function using 99mTc-IDA SPECT

    PubMed Central

    Wang, Hesheng; Cao, Yue

    2013-01-01

    Purpose: 99mTc-iminodiacetic acid (IDA) hepatobiliary imaging is usually quantified for hepatic function on the entire liver or regions of interest (ROIs) in the liver. The authors presented a method to estimate the hepatic extraction fraction (HEF) voxel-by-voxel from single-photon emission computed tomography (SPECT)/CT with a 99mTc-labeled IDA agent of mebrofenin and evaluated the spatially resolved HEF measurements with an independent physiological measurement. Methods: Fourteen patients with intrahepatic cancers were treated with radiation therapy (RT) and imaged by 99mTc-mebrofenin SPECT before and 1 month after RT. The dynamic SPECT volumes were with a resolution of 3.9 × 3.9 × 2.5 mm3. Throughout the whole liver with approximate 50 000 voxels, voxelwise HEF quantifications were estimated and compared between using arterial input function (AIF) from the heart and using vascular input function (VIF) from the spleen. The correlation between mean of the HEFs over the nontumor liver tissue and the overall liver function measured by Indocyanine green clearance half-time (T1/2) was assessed. Variation of the voxelwise estimation was evaluated in ROIs drawn in relatively homogeneous regions of the livers. The authors also examined effects of the time range parameter on the voxelwise HEF quantification. Results: Mean of the HEFs over the liver estimated using AIF significantly correlated with the physiological measurement T1/2 (r = 0.52, p = 0.0004), and the correlation was greatly improved by using VIF (r = 0.79, p < 0.0001). The parameter of time range for the retention phase did not lead to a significant difference in the means of the HEFs in the ROIs. Using VIF and a retention phase time range of 7–30 min, the relative variation of the voxelwise HEF in the ROIs was 10% ± 6% of respective mean HEF. Conclusions: The voxelwise HEF derived from 99mTc-IDA SPECT by the deconvolution analysis is feasible to assess the spatial distribution of hepatic function in

  2. 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

  3. 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.

  4. [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.

  5. 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

  6. 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.

  7. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    PubMed

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Imaging prostate cancer (PCa) with [99m Tc(CO)3 ]finasteride dithiocarbamate.

    PubMed

    Shah, Syed Qaiser; Gul-E-Raana; Uddin, Ghias

    2018-06-15

    This investigation aimed to modify finasteride (1) to finasteride dithiocarbamate (2) for subsequent synthesis of the rhenium analogue (3) and [ 99m Tc]tricarbonyl complexes (4), to assess its prostate cancer (PCa) targeting potential in a rat model. To validate the identity of (4), reference (3) has been synthesized by using fac-[Net 4 ] 2 [ReBr 3 (CO) 3 ] precursor and characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and elemental analysis. The analogue (4) was synthesized by using fac-[ 99m Tc(H 2 O) 3 (CO) 3 ] + precursor, and its structure was confirmed by comparative HPLC by using (3) as a reference. Further, the suitability of (4) as a PCa imaging agent was investigated in vitro and in vivo. At room temperature, (4) had ≥99% radiochemical purity and remained ≥84% stable in serum. In preclinical studies, biodistribution of (4) in histopathologically established rat model showed adequately high in vivo uptake in the prostate attracting the possibility of using it for noninvasive imaging of PCa. Copyright © 2018 John Wiley & Sons, Ltd.

  19. 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

  20. Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis.

    PubMed

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D; Szkudlinski, Mariusz W; Agostinelli, Enzo; Dierckx, Rudi A J O; Signore, Alberto

    2017-06-01

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with immunohistochemical analysis of excised tumors we found an inverse correlation between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive correlation with VEGF receptor expression (VEGFR1). Results of our studies indicate that endogenous VEGF production by cancer cells and other cells of tumor microenvironment should be taken in consideration when performing scintigraphy with radiolabeled VEGF, because of possible false negative results due to saturation of VEGFRs.

  1. The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

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

    Provoost, A.P.; Van Aken, M.

    1984-01-01

    In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. Themore » accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.« less

  2. 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.

  3. 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.

  4. Cold hematoma visualized by technetium-99m labeled red blood cells

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

    Beanblossom, M.

    1986-09-01

    A 64-yr-old male was admitted to the hospital with severe abdominal pain associated with vomiting. Upon examination, the patients Hgb was 7.8 with a WBC count of 13.3 band cells of 7 and a recticulocyte count of 3.4, no evidence of gastrointestinal bleeding. The patient's prior history revealed involvement in an automobile accident approx. 10 days prior to this admission. At that time, he suffered multiple contusions and abrasions with a fracture to his left clavicle. Apparently there were no episodes of abdominal pain or vomiting prior to the onset of illness perceived on the day of admission. A liver/spleenmore » scan was done. Four millicuries of /sup 99m/Tc-sulfur colloid were intravenously injected using a bolus injection technique while obtaining multiple dynamic images. The flow study was unremarkable, demonstrating no abnormalities to the great vessels and good perfusion to both organs. Static images of the liver and spleen revealed a straightening or flatness to the lateral border of the spleen with a small diminished area of tracer sulfur colloid localization at the posterolateral aspect of that organ. This finding raised the suspicion that a small subcapsular hematoma had developed at the mid-posterolateral aspect of the spleen. Twenty-four hours after hospital admission, 4 units of packed RBCs were transfused into the patient. Although there was at this time still no evidence of abnormal bleeding, it was felt that because of the strong symptomatic correlation for internal bleeding, a radionuclide bleeding site study should be ordered and immediately performed.« less

  5. 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.

  6. 99mTc-EDDA/HYNIC-TOC somatostatin receptor scintigraphy in daily clinical practice.

    PubMed

    Chrapko, Beata Ewa; Nocuń, Anna; Gołebiewska, Renata; Stefaniak, Bogusław; Korobowicz, Elzbieta; Czekajska-Chehab, Elzbieta; Sawicki, Marek; Polkowski, Wojciech Piotr

    2010-04-01

    This study aimed to assess the impact of 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) somatostatin receptor scintigraphy (SRS) in clinical practice. One hundred seventeen patients were divided into 6 groups: 1, initial detection and localization of suspected neuroendocrine tumor (NET); 2, tumor staging before therapy; 3, staging of NET of unknown origin, 4, restaging after surgery of primary tumor; 5, diagnosis of solitary pulmonary nodules (SPNs), and 6, follow-up after "cold" somatostatin analogues treatment. In group 1, clinical suspicions were not confirmed in any of the patients; in group 2, most of the primary lesions showed overexpression of somatostatin receptors (SSRT); in group 3, the primary tumor was not identified in any of the patients; in group 4, recurrences were depicted in 7 out of 47 patients; in group 5, only 1 malignant SPN was detected, and in group 6, regression of primary mass and metastases were seen on follow-up SRS in 1 patient. 99mTc-TOC SRS is useful in staging of SSRT-overexpressing tumors of known and unknown primary origin, as well as in restaging after primary tumor surgery. This method is less effective in detecting suspected NET and assessing SPNs. Further investigation is necessary to evaluate the usefulness of SRS in monitoring patients after biological treatment.

  7. 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

  8. Preliminary investigation of PAGAT polymer gel radionuclide dosimetry of Tc-99m

    NASA Astrophysics Data System (ADS)

    Braun, Kelly; Bailey, Dale; Hill, Brendan; Baldock, Clive

    2009-05-01

    PAGAT polymer gel was investigated as a suitable dosimeter materials for measuring absorbed dose from the unsealed source radionuclide Tc-99m. Differing amounts of Tc-99m over the range of 25-5000 MBq were introduced into a normoxic polymer gel mixture (PAGAT) in sealed nitrogen-filled P6 glass vials. After irradiation the gels were evaluated using MRI more than 48 hours after preparation to allow for radioactive decay. The dose delivered to the vial was also calculated empirically. R2 versus total activity curves were obtained over a number of experiments and these were used to evaluate the relationship between the amount of gel polymerization and the dose deposited by the radionuclide. A linear response up to 1000 MBq (corresponding to 20Gy) was displayed and was still behaving monotonically at 5000 MBq. Polymer gels offer the potential to measure radiation dose three-dimensionally using MRI.

  9. 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.

  10. Effect of increased surface tension and assisted ventilation on /sup 99m/Tc-DTPA clearance

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

    Jefferies, A.L.; Kawano, T.; Mori, S.

    1988-02-01

    Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreasedmore » arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. /sup 99m/Tc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP (k = 7.57 +/- 0.71%/min (SE)) and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of /sup 99m/Tc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.« less

  11. 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.

  12. 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

  13. 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.

  14. Use of Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) to determine hepatic blood flow

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

    Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

    1984-01-01

    Tc-NGA is a new liver radiopharmaceutical which binds to a hepatocyte-specific membrane receptor. Three characteristics of Tc-NGA can be exploited in the measurement of hepatic blood flow (HBF): 1) ability to alter the affinity of Tc-NGA for its receptor by changing the galactose: albumin ratio; 2) ability to achieve a high specific activity with Tc-99m labeling; and 3) ability to administer a high molar dose of Tc-NGA without physiologic side effects. In addition, kinetic modeling of Tc-NGA dynamic data can provide estimates of hepatic receptor concentration. In experimental studies in young pigs, HBF was determined using two techniques: 1) kineticmore » modeling of dynamic data using moderate affinity, low specific activity Tc-NGA (Group A, n=12); and 2) clearance (CL) technique using high affinity, high specific activity Tc-NGA (Group B, n=4). In both groups, HBF was determined simultaneously by continuous infusion of indocyanine green (CI-ICG) with hepatic vein sampling. Regression analysis of HBF measurements obtained with the Tc-NGA kinetic modeling technique and the CI-ICG technique (Group A) revealed good correlation between the two techniques (r=0.802, p=0.02). Similarly, HBF determination by the clearance technique (Group B) provided highly accurate measurements when compared to the CI-ICG technique. Hepatic blood flow measurements by the clearance technique (CL-NGA) fell within one standard deviation of the error associated with each CI-ICG HBF measurement (all CI-ICG standard deviations were less than 10%).« less

  15. 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.

  16. 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

  17. A novel Tc-99m 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-99m and TAMRA to target the integrin α V β 3 of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99m 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-99m 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-99m, the Tc-99m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). In the gamma camera imaging study, a substantial uptake of Tc-99m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin α V β 3 positive) and low uptake of Tc-99m 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-99m 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-99m TAMRA-GHEG-ECG-SDV in the integrin α V β 3 -positive tumor. Tc-99m 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.

  18. 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.

  19. Viable myocardium scintigraphy with intravenous nitroglycerine by computed tomography with Tc-99m (MIBI).

    PubMed

    Ramos Filho, José; Nascimento, Marcos Welber; Silva, Rafael Mariano Gislon da; Camargo, Thiago Negrini de; Almeida, Roberto Simões de; Lima, Eloá Jacinto

    2008-09-01

    The selection of patients with chronic coronary disease for recanalization is based on the detection of the affected myocardium that is potentially viable. To evaluate the potentially viable ischemic myocardium through single photon emission computed tomography (SPECT) with MIBI after a maximum tolerated dose of I.V. nitroglycerin. We prospectively investigated by SPECT with Tc-99m (MIBI), from April 2004 to November 2005, 40 patients (mean age: 62 +/- 8.9 yrs, 30 men) with coronary obstruction demonstrated angiographically; the myocardium scintigraphy was carried out at rest and after intravenous (I.V.) nitroglycerin, which was started at a dose of 1 microg/kg/min and increased every minute until the systolic blood pressure decreased by 20 mmHg. The decrease in the perfusion of the segments was classified as moderate or severe and compared after the nitroglycerin. The angiographic, hemodynamic and myocardial perfusion variables were analyzed. We analyzed 680 myocardial segments at rest: 538 with a homogenous distribution and 142 with hypoperfusion (54 with moderate and 88 with severe decrease). After the nitroglycerin, there was an increase in the perfusion in 19 (47.5%) of 40 patients and 55 of 142 segments became viable: 33 (61.1%) with moderate and 22 (25%) with severe decrease; both presented a significant increase in the radiotracer distribution (p < 0.001, Chi-square). One of the components with Tc-99m is Tc-99m 2-methoxy-isobutyl-isonitrile (MIBI), which, when used with an optimized dose of I.V. nitroglycerin, can increase the radiotracer uptake in areas with moderate and severe hypoperfusion. The results of the present study suggest the increase in the Tc-99m (MIBI) sensitivity by nitroglycerin for the detection of viable myocardium.

  20. 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

  1. 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.

  2. (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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Biological Evaluation of 99mTc-HYNIC-EDDA/tricine-(Ser)-D4 Peptide for Tumor Targeting.

    PubMed

    Kazemi, Ziba; Zahmatkesh, Mona Haddad; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2017-08-24

    D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice. This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection. This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Structural characterization of a bridged 99Tc-Sn-dimethylglyoxime complex: implications for the chemistry of 99mTc-radiopharmaceuticals prepared by the Sn (II) reduction of pertechnetate.

    PubMed Central

    Deutsch, E; Elder, R C; Lange, B A; Vaal, M J; Lay, D G

    1976-01-01

    Reduction of pertechnetate by tin(II) in the presence of dimethylglyoxime is shown, by single crystal x-ray analysis, to yield a technetium-tin-dimethylglyoxime complex in which tin and technetium are intimately connected by a triple bridging arrangement. One bridge consists of a single oxygen atom and it is hypothesized that this bridge arises from the inner sphere reduction of technetium by tin(II), the electrons being transferred through a technetium "yl" oxygen which eventually becomes the bridging atom. Two additional bridges arise from two dimethylglyoxime ligands that function as bidentate nitrogen donors towards Tc and monodentate oxygen donors towards Sn. The tin atom can thus be viewed as providing a three-pronged "cap" on one end of the Tc-dimethylglyoxime complex. The additional coordination sites around Tc are occupied by the two nitrogens of a third dimethylglyoxime ligand, making the Tc seven-coordinate. The additional coordination sites around Sn are occupied by three chloride anions, giving the Sn a fac octahedral coordination environment. From indirect evidence the oxidation states of tin and technetium are tentatively assigned to be IV and V, respectively. Since most 99mTc-radiopharmaceuticals are synthesized by the tin(II) reduction of pertechnetate, it is likely that the Sn-O-Tc linkage described in this work is an important feature of the chemistry of these species. This linkage also provides a ready rationale for the close association of tin and technetium observed in many 99mTc-radiopharmaceuticals. PMID:1069984

  14. Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha-MSH peptide.

    PubMed

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

    2017-11-15

    The purpose of this study was to determine the metastatic melanoma imaging property of 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex {hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 }. HYNIC-Aoc-Nle-CycMSH hex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The IC 50 value of HYNIC-Aoc-Nle-CycMSH hex was 0.78 ± 0.13 nM for B16/F10 melanoma cells. 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex displayed significantly higher uptake (14.26 ± 2.74 and 10.45 ± 2.31% ID/g) in B16/F10 metastatic melanoma-bearing lung than that in normal lung (0.90 ± 0.15 and 0.53 ± 0.14% ID/g) at 2 and 4 h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-Aoc-Nle-CycMSH hex as an imaging probe at 2 h post-injection, underscoring its potential as an imaging probe for metastatic melanoma detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Development of 99mTc-radiolabeled nanosilica for targeted detection of HER2-positive breast cancer

    PubMed Central

    Rainone, Paolo; Riva, Benedetta; Belloli, Sara; Sudati, Francesco; Ripamonti, Marilena; Verderio, Paolo; Colombo, Miriam; Colzani, Barbara; Gilardi, Maria Carla; Moresco, Rosa Maria; Prosperi, Davide

    2017-01-01

    The human epidermal growth factor receptor 2 (HER2) is normally associated with a highly aggressive and infiltrating phenotype in breast cancer lesions with propensity to spread into metastases. In clinic, the detection of HER2 in primary tumors and in their metastases is currently based on invasive methods. Recently, nuclear molecular imaging techniques, including positron emission tomography and single photon emission computed tomography (SPECT), allowed the detection of HER2 lesions in vivo. We have developed a 99mTc-radiolabeled nanosilica system, functionalized with a trastuzumab half-chain, able to act as drug carrier and SPECT radiotracer for the identification of HER2-positive breast cancer cells. To this aim, nanoparticles functionalized or not with trastuzumab half-chain, were radiolabeled using the 99mTc-tricarbonyl approach and evaluated in HER2 positive and negative breast cancer models. Cell uptake experiments, combined with flow cytometry and fluorescence imaging, suggested that active targeting provides higher efficiency and selectivity in tumor detection compared to passive diffusion, indicating that our radiolabeling strategy did not affect the nanoconjugate binding efficiency. Ex vivo biodistribution of 99mTc-nanosilica in a SK-BR-3 (HER2+) tumor xenograft at 4 h postinjection was higher in targeted compared to nontargeted nanosilica, confirming the in vitro data. In addition, viability and toxicity tests provided evidence on nanoparticle safety in cell cultures. Our results encourage further assessment of silica 99mTc-nanoconjugates to validate a safe and versatile nanoreporter system for both diagnosis and treatment of aggressive breast cancer. PMID:28496321

  2. 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.

  3. Combining imaging and anticancer properties with new heterobimetallic Pt(ii)/M(i) (M = Re, 99mTc) complexes.

    PubMed

    Quental, Letícia; Raposinho, Paula; Mendes, Filipa; Santos, Isabel; Navarro-Ranninger, Carmen; Alvarez-Valdes, Amparo; Huang, Huaiyi; Chao, Hui; Rubbiani, Riccardo; Gasser, Gilles; Quiroga, Adoración G; Paulo, António

    2017-10-31

    In this article, we report on the development of new metal-based anticancer agents with imaging, chemotherapeutic and photosensitizing properties. Hence, a new heterobimetallic complex (Pt-LQ-Re) was prepared by connecting a non-conventional trans-chlorido Pt(ii) complex to a photoactive Re tricarbonyl unit (LQ-Re), which can be replaced by 99m Tc to allow for in vivo imaging. We describe the photophysical and biological properties of the new complexes, in the dark and upon light irradiation (DNA interaction, cellular localization and uptake, and cytotoxicity). Furthermore, planar scintigraphic images of mice injected with Pt-LQ-Tc clearly showed that the radioactive compound is taken up by the excretory system organs, namely liver and kidneys, without significant retention in other tissues. All in all, the strategy of conjugating a chemotherapeutic compound with a PDT photosensitizer endows the resulting complexes with an intrinsic cytotoxic activity in the dark, driven by the non-classical platinum core, and a selective activity upon light irradiation. Most importantly, the possibility of integrating a SPECT imaging radiometal ( 99m Tc) in the structure of these new heterobimetallic complexes might allow for in vivo non-invasive visualization of their tumoral accumulation, a crucial issue to predict therapeutic outcomes.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Synthesis and evaluation of a 99mTc-labeled tubulin-binding agent for tumor imaging.

    PubMed

    Erfani, Mostafa; Shamsaei, Mojtaba; Mohammadbaghery, Faiyaz; Shirmardi, Seyed Pezhman

    2014-05-30

    Cholchicine and its derivatives are very potent tubulin-binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with (99m) Tc via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with (99m)Tc was performed at 95 °C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 °C up to 24 h. Biodistribution was studied in breast tumor-bearing mice. Labeling yield of 95.8 ± 0.54% was obtained corresponding to a specific activity of 54 MBq/µmol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor-bearing mice showed that (99m) Tc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 ± 0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging. Copyright © 2014 John Wiley & Sons, Ltd.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

    PubMed

    Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

    2016-01-01

    Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

  16. Multimodality imaging using SPECT/CT and MRI and ligand functionalized 99mTc-labeled magnetic microbubbles

    PubMed Central

    2013-01-01

    Background In the present study, we used multimodal imaging to investigate biodistribution in rats after intravenous administration of a new 99mTc-labeled delivery system consisting of polymer-shelled microbubbles (MBs) functionalized with diethylenetriaminepentaacetic acid (DTPA), thiolated poly(methacrylic acid) (PMAA), chitosan, 1,4,7-triacyclononane-1,4,7-triacetic acid (NOTA), NOTA-super paramagnetic iron oxide nanoparticles (SPION), or DTPA-SPION. Methods Examinations utilizing planar dynamic scintigraphy and hybrid imaging were performed using a commercially available single-photon emission computed tomography (SPECT)/computed tomography (CT) system. For SPION containing MBs, the biodistribution pattern of 99mTc-labeled NOTA-SPION and DTPA-SPION MBs was investigated and co-registered using fusion SPECT/CT and magnetic resonance imaging (MRI). Moreover, to evaluate the biodistribution, organs were removed and radioactivity was measured and calculated as percentage of injected dose. Results SPECT/CT and MRI showed that the distribution of 99mTc-labeled ligand-functionalized MBs varied with the type of ligand as well as with the presence of SPION. The highest uptake was observed in the lungs 1 h post injection of 99mTc-labeled DTPA and chitosan MBs, while a similar distribution to the lungs and the liver was seen after the administration of PMAA MBs. The highest counts of 99mTc-labeled NOTA-SPION and DTPA-SPION MBs were observed in the lungs, liver, and kidneys 1 h post injection. The highest counts were observed in the liver, spleen, and kidneys as confirmed by MRI 24 h post injection. Furthermore, the results obtained from organ measurements were in good agreement with those obtained from SPECT/CT. Conclusions In conclusion, microbubbles functionalized by different ligands can be labeled with radiotracers and utilized for SPECT/CT imaging, while the incorporation of SPION in MB shells enables imaging using MR. Our investigation revealed that biodistribution

  17. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

    PubMed

    Artiko, Vera; Afgan, Aida; Petrović, Jelena; Radović, Branislava; Petrović, Nebojša; Vlajković, Marina; Šobić-Šaranović, Dragana; Obradović, Vladimir

    2016-01-01

    This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p < 0.01) on SPECT (3.12 ± 1.13) than on whole body scan (2.2 ± 0.75). According to our results, overall sensitivity of the method is 80%, specificity 92%, positive predictive value 98%, negative predictive value 47% and accuracy 82%. Fifteen TP patients underwent therapy with 90Y-DOTATATE. Scintigraphy of neuroendocrine tumors with 99mTc-Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

  18. 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.

  19. 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

  20. Diagnostic value of 99mTc-bombesin scintigraphy for differentiation of malignant from benign breast lesions.

    PubMed

    Shariati, Farzaneh; Aryana, Kamran; Fattahi, Asiehsadat; Forghani, Mohammad N; Azarian, Azita; Zakavi, Seyed R; Sadeghi, Ramin; Ayati, Narjes; Sadri, Keyvan

    2014-06-01

    In this study, we evaluated the diagnostic accuracy of (99m)Tc-bombesin scintigraphy for differentiation of benign from malignant palpable breast lesions. (99m)Tc-Bombesin is a tracer with high affinity for gastrin-releasing peptide receptor, which is overexpressed on a variety of human tumors including breast carcinoma. We examined 33 consecutive women who were referred to our center with suspicious palpable breast lesions but had no definitive diagnosis in other imaging procedures. A volume of 370-444 MBq of (99m)Tc-bombesin was injected and dynamic 1-min images were taken for 20 min immediately after injection in anterior view. Thereafter, two static images in anterior and prone-lateral views were taken for 5 min. Finally, single-photon emission computed tomography images were taken for each patient. Definitive diagnosis was based on biopsy and histopathological evaluation. The scan findings were positive in 19 patients and negative in 11 on visual assessment of the planar and single-photon emission computed tomography images. Pathologic examination confirmed breast carcinoma in 12 patients with positive scans and benign pathology for 18 patients. The overall sensitivity, specificity, negative and positive predictive values, and accuracy of this radiotracer for diagnosis of breast cancer were 100, 66.1, 100, 63, and 76%, respectively. Semiquantitative analysis improved the specificity of the visual assessment from 66 to 84%. Our study showed that (99m)Tc-bombesin scintigraphy has a high sensitivity and negative predictive value for detecting malignant breast lesions, but the specificity and positive predictive value of this radiotracer for differentiation of malignant breast abnormalities from benign ones are relatively low.

  1. Influence of exercise on the distribution of technetium Tc 99m medronate following intra-articular injection in horses.

    PubMed

    Dulin, Jennifer A; Drost, W Tod; Phelps, Mitch A; Santschi, Elizabeth M; Menendez, Maria I; Bertone, Alicia L

    2012-03-01

    To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate ((99m)Tc-MDP) following intra-articular (IA) injection in horses. 5 horses. 1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of (99m)Tc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7. Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/μL; nonexercised, 948 ± 223 cells/μL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model. IA injection of (99m)Tc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of (99m)Tc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

  2. 99mTc-d,l-HMPAO and SPECT of the brain in normal aging

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

    Waldemar, G.; Hasselbalch, S.G.; Andersen, A.R.

    1991-05-01

    Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine oxime (99mTc-d,l-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21-83 years. For the whole group, global CBF normalized to the cerebellum was 86.4% +/- 8.4 (SD). The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise multiple regression analysis. There was a significant negative correlation of global CBF with subjective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age. In a subgroup of 33 subjects, in whom volumetric measurements of atrophy were performed,more » cortical atrophy was the only significant determinant for global CBF, accounting for 27% of its variance. Mean global CBF as measured with the 133Xe inhalation technique and SPECT was 54 +/- 9 ml/100 g/min and did not correlate significantly with age. There was a preferential decline of CBF in the frontal cortex with advancing age. The side-to-side asymmetry of several regions of interest increased with age. A method was described for estimation of subcortical CBF, which decreased with advancing cortical atrophy. The relative area of the subcortical low-flow region increased with age. These results are useful in distinguishing the effects of age and simple atrophy from disease effects, when the 99mTc-d,l-HMPAO method is used.« less

  3. [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

  4. Clickable, hydrophilic ligand for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) applied in an S-functionalized α-MSH peptide.

    PubMed

    Kasten, Benjamin B; Ma, Xiaowei; Liu, Hongguang; Hayes, Thomas R; Barnes, Charles L; Qi, Shibo; Cheng, Kai; Bottorff, Shalina C; Slocumb, Winston S; Wang, Jing; Cheng, Zhen; Benny, Paul D

    2014-03-19

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[M(I)(CO)3](+) (M = Re/(99m)Tc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[(99m)Tc(I)(CO)3](+) complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[Re(I)(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[(99m)Tc(I)(OH2)3(CO)3](+). The corresponding (99m)Tc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[M(I)(CO)3](+) using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[M(I)(CO)3](+) complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR's and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[M(I)(CO)3](+) using this synthetic route. The fac-[M(I)(CO)3](+)-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells

  5. 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.

  6. 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.

  7. Comparative in vivo evaluation of two novel 99mTc labelled bombesin derivatives

    NASA Astrophysics Data System (ADS)

    Gourni, Eleni; Bouziotis, Penelope; Zikos, Christos; Loudos, George; Xanthopoulos, Stavros; Fani, Melpomeni; Archimandritis, Spyridon C.; Varvarigou, Alexandra D.

    2006-12-01

    Bombesin (BN), a 14 amino acid peptide, is an analogue of human gastrin-releasing-peptide (GRP) that binds to GRP receptors (GRP-R) with high affinity and specificity. In addition to this physiological role, GRP, through its interaction with GRP-R, promotes tumour growth in a number of human cancer cell lines. The GRP receptors are over-expressed on a variety of human cancer cells. Aim of the present work is the study of two novels BN-like peptides, by investigating the radiochemical and radiopharmacological behaviour of their complexes with metals. The derivatives under study are: Gly-Gly-Cys-Aca-BN [2-14] where Aca: 6-amino-hexanoic acid. Pyroglutamic acid in the bombesin molecule has been replaced by the chemical group Gly-Gly-Cys-Aca, which bears an amino-acid combination capable of complexing a variety of radiometals. The other derivative under study is: Gly-Gly-Cys-Aca-BN [7-14]. This moiety of the peptide has been chosen because it has been proven to be a potent GRP agonist. The peptide derivatives were synthesized by SPPS, according to the Fmoc strategy and were identified by reverse phase high performance liquid chromatography (RP-HPLC). Radiolabelling with 99mTc was performed via the precursor 99mTc-gluconate. The stability of the radiolabelled species was examined with time. In vivo studies of the two 99mTc-labelled derivatives were performed, comparatively, in normal mice, attention being focused on GRP receptor-bearing organs, and in experimentally induced prostate cancer models. Experimental tumours were imaged in a small field-of-view animal gamma camera.

  8. 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

  9. [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.

  10. 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.

  11. 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.

  12. 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.

  13. Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.

    PubMed

    Niikura, Hitoshi; Okamura, Chikako; Akahira, Junichi; Takano, Tadao; Ito, Kiyoshi; Okamura, Kunihiro; Yaegashi, Nobuo

    2004-08-01

    The purpose of this study was to examine sentinel lymph node (SLN) detection in patients with early stage cervical cancer using (99m)Tc phytate and patent blue dye and to compare our method with published findings utilizing other radioisotopic tracers. A total of 20 consecutive patients with cervical cancer scheduled for radical hysterectomy and total pelvic lymphadenectomy at our hospital underwent SLN detection study. The day before surgery, lymphoscintigraphy was performed with injection of 99m-technetium ((99m)Tc)-labeled phytate into the uterine cervix. At surgery, patients underwent lymphatic mapping with a gamma-detecting probe and patent blue injected into the same points as the phytate solution. At least one positive node was detected in 18 patients (90%). A total of 46 sentinel nodes were detected (mean, 2.3; range, 1-5). Most sentinel nodes were in one of the following sites: external iliac (21 nodes), obturator (15 nodes), and parametrial (7 nodes). Eleven (24%) sentinel nodes were detected only through radioactivity and two (4%) were detected only with blue dye. The sensitivity, specificity, and negative predictive value for SLN detection were all 100%. Nine published studies involving 295 patients had a summarized detection rate of 85%. Summarized sensitivity, specificity, and negative predictive value were 93%, 100%, and 99%, respectively. Combination of (99m)Tc phytate and patent blue is effective in SLN detection in early stage cervical cancer.

  14. Preclinical Biokinetic Modelling of Tc-99m Radiophamaceuticals Obtained from Semi-Automatic Image Processing.

    PubMed

    Cornejo-Aragón, Luz G; Santos-Cuevas, Clara L; Ocampo-García, Blanca E; Chairez-Oria, Isaac; Diaz-Nieto, Lorenza; García-Quiroz, Janice

    2017-01-01

    The aim of this study was to develop a semi automatic image processing algorithm (AIPA) based on the simultaneous information provided by X-ray and radioisotopic images to determine the biokinetic models of Tc-99m radiopharmaceuticals from quantification of image radiation activity in murine models. These radioisotopic images were obtained by a CCD (charge couple device) camera coupled to an ultrathin phosphorous screen in a preclinical multimodal imaging system (Xtreme, Bruker). The AIPA consisted of different image processing methods for background, scattering and attenuation correction on the activity quantification. A set of parametric identification algorithms was used to obtain the biokinetic models that characterize the interaction between different tissues and the radiopharmaceuticals considered in the study. The set of biokinetic models corresponded to the Tc-99m biodistribution observed in different ex vivo studies. This fact confirmed the contribution of the semi-automatic image processing technique developed in this study.

  15. 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.

  16. 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.

  17. Evaluation of 99mTc-MIBI in thyroid gland imaging for the diagnosis of amiodarone-induced thyrotoxicosis

    PubMed Central

    Zhang, Ruiguo

    2017-01-01

    Objective: Amiodarone-induced thyrotoxicosis (AIT) is caused by amiodarone as a side effect of cardiovascular disease treatment. Based on the differences in their pathological and physiological mechanisms, many methods have been developed so far to differentiate AIT subtypes such as colour flow Doppler sonography (CFDS) and 24-h radioiodine uptake (RAIU). However, these methods suffer from inadequate accuracy in distinguishing different types of AITs and sometimes lead to misdiagnosis and delayed treatments. Therefore, there is an unmet demand for an efficient method for accurate classification of AIT. Methods: Technetium-99 methoxyisobutylisonitrile (99mTc-MIBI) thyroid imaging was performed on 15 patients for AIT classification, and the results were compared with other conventional methods such as CFDS, RAIU and 99mTcO4 imaging. Results: High uptake and retention of MIBI in thyroid tissue is characteristic in Type I AIT, while in sharp contrast, low uptake of MIBI in the thyroid tissue was observed in Type II AIT. Mixed-type AIT shows uptake value between Types I and II. MIBI imaging outperforms other methods with a lower misdiagnosis rate. Conclusion: Among the methods evaluated, MIBI imaging enables an accurate identification of Type I, II and mixed-type AITs by showing distinct images for different types of AITs. The results obtained from our selected subjects revealed that MIBI imaging is a reliable method for diagnosis and classification of AITs and MIBI imaging has potential in the treatment of thyroid diseases. Advances in knowledge: 99mTc-MIBI imaging is a useful method for the diagnosis of AIT. It can distinguish different types of AITs especially for mixed-type AIT, which is usually difficult to treat. 99mTc-MIBI has potential advantages over conventional methods in the efficient treatment of AIT. PMID:28106465

  18. 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.

  19. 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

  20. 2-Phenylbenzothiazole conjugated with cyclopentadienyl tricarbonyl [CpM(CO)3] (M = Re, (99m)Tc) complexes as potential imaging probes for β-amyloid plaques.

    PubMed

    Jia, Jianhua; Cui, Mengchao; Dai, Jiapei; Liu, Boli

    2015-04-14

    Technetium-99m-labeled cyclopentadienyl tricarbonyl complexes conjugated with the 2-phenylbenzothiazole binding motif were synthesized. The rhenium surrogates , , and were demonstrated to have moderate to high affinities for Aβ1-42 aggregates with Ki values of 142, 76, 64 and 24 nM, respectively. During the fluorescence staining of brain sections of transgenic mice and patients with Alzheimer's disease, these rhenium complexes demonstrated perfect and intense labeling of Aβ plaques. Moreover, in in vitro autoradiography, (99m)Tc-labeled complexes clearly detected β-amyloid plaques on sections of brain tissue from transgenic mice, which confirmed the sufficient affinity of these tracers for Aβ plaques. However, these compounds did not show desirable properties in vivo, especially showing poor brain uptake (below 0.5% ID g(-1)), which will hinder the further development of these tracers as brain imaging agents. Nonetheless, it is encouraging that these (99m)Tc-labeled complexes designed by a conjugate approach displayed sufficient affinities for Aβ plaques.

  1. 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.

  2. 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.

  3. Non-Q-wave myocardial infarction: impaired myocardial energy metabolism in regions with reduced 99mTc-MIBI accumulation.

    PubMed

    Moka, D; Baer, F M; Theissen, P; Schneider, C A; Dietlein, M; Erdmann, E; Schicha, H

    2001-05-01

    Reduced regional technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) accumulation in patients with chronic non-Q-wave infarction (NQWI) but without significant coronary artery stenosis indicates non-transmural damage of the myocardial wall. The aim of this study was to characterise cardiac energy metabolism after NQWI using phosphorus-31 magnetic resonance spectroscopy (31P-MRS) and to compare the biochemical remodelling with changes in regional 99mTc-MIBI uptake and with morphological and functional parameters assessed by magnetic resonance imaging (MRI). Fifteen patients with a history of NQWI, exclusion of significant coronary artery stenosis (<50% diameter stenosis) and hypokinesia of the anterior wall (group A) were examined with 31P-MRS to study the effects of NQWI on myocardial energy metabolism. Spectroscopic measurements were performed in the infarct-related myocardial region. Corresponding gradient-echo MR images and myocardial 99mTc-MIBI single-photon emission tomography images were acquired for exact localisation of the infarct region. All examinations were performed at rest under anti-ischaemic medication. Data were compared with those of patients in whom coronary artery disease had been excluded by angiography (group B, n=10). All patients of group A displayed anterior wall hypokinesia in the infarcted area on both ventriculography and MRI, with a reduced myocardial accumulation of 99mTc-MIBI (66.3%+/-11.8% vs 95.6%+/-2.2% in group B). The mean wall thickness during the complete cardiac cycle (9.5+/-1.8 mm vs 13.1+/-1.1 mm in group B, P<0.001), the systolic wall thickening (2.6+/-1.4 mm vs 5.8+/-1.5 mm in group B, P<0.01) and the phosphocreatine/adenosine triphosphate ratio (1.12+/-0.22 vs 1.74+/-0.23 in group B, P<0.01) in the hypokinetic area were all significantly reduced. It is concluded that persisting hypokinetic myocardium after NQWI combined with reduced myocellular uptake of 99mTc-MIBI displays a reduced PCr/ATP ratio. Our results indicate

  4. 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

  5. Multicenter Trial of Sentinel Node Biopsy for Breast Cancer Using Both Technetium Sulfur Colloid and Isosulfan Blue Dye

    PubMed Central

    Tafra, Lorraine; Lannin, Donald R.; Swanson, Melvin S.; Van Eyk, Jason J.; Verbanac, Kathryn M.; Chua, Arlene N.; Ng, Peter C.; Edwards, Maxine S.; Halliday, Bradford E.; Henry, C. Alan; Sommers, Linda M.; Carman, Claire M.; Molin, Melinda R.; Yurko, John E.; Perry, Roger R.; Williams, Robert

    2001-01-01

    Objective To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). Summary Background Data Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. Methods Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. Results Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. Conclusions This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an

  6. 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.

  7. 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.

  8. Organ distribution of technetium-99m-labeled Corynebacterium parvum in normal and tumor-bearing mice

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

    Barth, R.F.; Singla, O.

    1978-01-01

    The distribution patterns were studied for /sup 99m/Tc-labeled Corynebacterium parvum in normal and tumor-bearing mice. C57BL/6 mice were given i.v., i.p., or s.c. injections of 250 ..mu..g of /sup 99m/Tc-labeled C. parvum and killed at 10 min, 1, 4, and 24 hr. After iv. administration, labeled organisms were distributed primarily to the liver, the lungs, and the blood (46% of injected dose), followed by the gastrointestinal tract, the spleen, and the kidneys (11%). Total recoverable radioactivity, which was defined as the percentage of injected dose that was recovered, ranged from 59% at 10 min to 15% at 24 hr. Inmore » contrast to this, /sup 99m/TcS colloid, an inert particulate material, was localized almost entirely in the liver, and the amount recoverable remained constant over 24 hr. One hr after i.p. administration of /sup 99m/Tc-labeled C. parvum, the gastrointestinal tract accounted for 27% of the injected radioactivity, followed by liver, blood, and spleen (12%). This was rapidly excreted between 4 and 24 hr, at which time only 12% of the injected dose was recovered. The skin accounted for 54.6% of the injected radioactivity 1 hr after s.c. injection, 6% 4 hr after s.c. injection, and 0.8% at 24 hr after s.c. injection.« less

  9. 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.

  10. Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.

    PubMed

    Burroni, L; Aucone, A M; Volterrani, D; Hayek, Y; Bertelli, P; Vella, A; Zappella, M; Vattimo, A

    1997-06-01

    Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.

  11. 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.

  12. Radiosynthesis and Biodistribution of 99mTc-Metronidazole as an Escherichia coli Infection Imaging Radiopharmaceutical.

    PubMed

    Iqbal, Anam; Naqvi, Syed Ali Raza; Rasheed, Rashid; Mansha, Asim; Ahmad, Matloob; Zahoor, Ameer Fawad

    2018-05-01

    Bacterial infection poses life-threatening challenge to humanity and stimulates to the researchers for developing better diagnostic and therapeutic agents complying with existing theranostic techniques. Nuclear medicine technique helps to visualize hard-to-diagnose deep-seated bacterial infections using radionuclide-labeled tracer agents. Metronidazole is an antiprotozoal antibiotic that serves as a preeminent anaerobic chemotherapeutic agent. The aim of this study was to develop technetium-99m-labeled metronidazole radiotracer for the detection of deep-seated bacterial infections. Radiosynthesis of 99m Tc-metronidazole was carried by reacting reduced technetium-99m and metronidazole at neutral pH for 30 min. The stannous chloride dihydrate was used as the reducing agent. At optimum radiolabeling conditions, ~ 94% radiochemical was obtained. Quality control analysis was carried out with a chromatographic paper and instant thin-layer chromatographic analysis. The biodistribution study of radiochemical was performed using Escherichia coli bacterial infection-induced rat model. The scintigraphic study was performed using E. coli bacterial infection-induced rabbit model. The results showed promising accumulation at the site of infection and its rapid clearance from the body. The tracer showed target-to-non-target ratio 5.57 ± 0.04 at 1 h post-injection. The results showed that 99m Tc-MNZ has promising potential to accumulate at E. coli bacterial infection that can be used for E. coli infection imaging.

  13. Comparison of estimated human dose of (68)Ga-MAA with (99m)Tc-MAA based on rat data.

    PubMed

    Shanehsazzadeh, Saeed; Lahooti, Afsaneh; Yousefnia, Hassan; Geramifar, Parham; Jalilian, Amir Reza

    2015-10-01

    (99m)Tc macroaggregated albumin ((99m)Tc-MAA) that had been used as a perfusion agent has been evaluated. In this study, we tried to estimate human absorbed dose of ⁶⁸Ga-MAA via commercially available kit from Pars-Isotopes, based on biodistribution data in wild-type rats, and compare our estimation with the available absorbed dose data from (99m)Tc-MAA. For biodistribution of ⁶⁸Ga-MAA, three rats were sacrificed at each selected times after injection (15, 30, 45, 60, and 120 min) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 11 harvested organs. The medical internal radiation dose formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. The biodistribution data for ⁶⁸Ga-MAA showed that the most of the activity was taken up by the lung (more than 97 %) in no time. Our dose prediction shows that a 185-MBq injection of ⁶⁸Ga-MAA into humans might result in an estimated absorbed dose of 4.31 mGy in the whole body. The highest absorbed doses are observed in the adrenals, spleen, pancreas, and red marrow with 0.36, 0.34, 0.26, and 0.19 mGy, respectively. Since the (99m)Tc-MAA remains longer than ⁶⁸Ga-MAA in the lung and ⁶⁸Ga-MAA has good image qualities and results in lower amounts of dose delivery to the critical organs such as gonads, red marrow, and adrenals, the use of ⁶⁸Ga-MAA is recommended.

  14. Standardization of Tc-99 by two methods and participation at the CCRI(II)-K2. Tc-99 comparison.

    PubMed

    Sahagia, M; Antohe, A; Ioan, R; Luca, A; Ivan, C

    2014-05-01

    The work accomplished within the participation at the 2012 key comparison of Tc-99 is presented. The solution was standardized for the first time in IFIN-HH by two methods: LSC-TDCR and 4π(PC)β-γ efficiency tracer. The methods are described and the results are compared. For the LSC-TDCR method, the program TDCR07c, written and provided by P. Cassette, was used for processing the measurement data. The results are 2.1% higher than when applying the TDCR06b program; the higher value, calculated with the software TDCR07c, was used for reporting the final result in the comparison. The tracer used for the 4π(PC)β-γ efficiency tracer method was a standard (60)Co solution. The sources were prepared from the mixture (60)Co+(99)Tc solution and a general extrapolation curve, type: N(βTc-99)/(M)(Tc-99)=f [1-ε(Co-60)], was drawn. This value was not used for the final result of the comparison. The difference between the values of activity concentration obtained by the two methods was within the limit of the combined standard uncertainty of the difference of these two results. © 2013 Published by Elsevier Ltd.

  15. 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.

  16. Preparation of 99mTc-TRODAT-1 with high labeling yield in boiling water bath: a new formulation.

    PubMed

    Erfani, Mostafa; Shafiei, Mohammad

    2014-04-01

    A new formulation for preparation of (99m)Tc-labeled tropane derivative, (99m)Tc-TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. Preparation of (99m)Tc-TRODAT-1 was attained previously by a formulation in which vial has to be autoclaved at 121 °C for 30 min. It is highly desirable to further improve the preparation method by developing a simplified one vial formulation which will be labeled in boiling water bath (95 °C) for 15 min and a high labeling yield will be achieved. A formulation contained 10 μg of TRODAT-1, 20 μg tricine, 40 μg SnCl2 and 20mg manitol was prepared. Labeling was performed at 95 °C for 15 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radioconjugate was checked in the presence of human serum at 37 °C up to 24h. (99m)Tc-TRODAT-1 was prepared with a radiochemical purity of more than 95% and specific activity of 64.3 MBq/nmol. Biodistribution studies of this new formulation in rats revealed similar regional brain distribution as compared with those obtained with the previous preparation in which brain uptake was high in striatum and striatum to cerebellum ratio was high. Requiring no autoclave facility for labeling, this new formulation will significantly improve the using feasibility of this radiopharmaceutical in clinic. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. (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.

  20. 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.

  1. Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

    PubMed

    Papantoniou, Vassilios; Tsaroucha, Angeliki; Valsamaki, Pipitsa; Tsiouris, Spyridon; Sotiropoulou, Evangelia; Karianos, Theodore; Marinopoulos, Spyridon; Fothiadaki, Athina; Sotiropoulou, Maria; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Dimitrakakis, Konstantinos; Antsaklis, Aris

    2010-10-01

    The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

  2. 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.

  3. Theoretical Modeling of (99)Tc NMR Chemical Shifts.

    PubMed

    Hall, Gabriel B; Andersen, Amity; Washton, Nancy M; Chatterjee, Sayandev; Levitskaia, Tatiana G

    2016-09-06

    Technetium-99 (Tc) displays a rich chemistry due to its wide range of accessible oxidation states (from -I to +VII) and ability to form coordination compounds. Determination of Tc speciation in complex mixtures is a major challenge, and (99)Tc nuclear magnetic resonance (NMR) spectroscopy is widely used to probe chemical environments of Tc in odd oxidation states. However, interpretation of (99)Tc NMR data is hindered by the lack of reference compounds. Density functional theory (DFT) calculations can help to fill this gap, but to date few computational studies have focused on (99)Tc NMR of compounds and complexes. This work evaluates the effectiveness of both pure generalized gradient approximation and their corresponding hybrid functionals, both with and without the inclusion of scalar relativistic effects, to model the (99)Tc NMR spectra of Tc(I) carbonyl compounds. With the exception of BLYP, which performed exceptionally well overall, hybrid functionals with inclusion of scalar relativistic effects are found to be necessary to accurately calculate (99)Tc NMR spectra. The computational method developed was used to tentatively assign an experimentally observed (99)Tc NMR peak at -1204 ppm to fac-Tc(CO)3(OH)3(2-). This study examines the effectiveness of DFT computations for interpretation of the (99)Tc NMR spectra of Tc(I) coordination compounds in high salt alkaline solutions.

  4. 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

  5. Evaluation of Nasal Mucociliary Transport Rate by99mTc-Macroaggregated Albumin Rhinoscintigraphy in Woodworkers

    PubMed Central

    Dostbil, Zeki; Polat, Cahit; Uysal, İsmail Önder; Bakır, Salih; Karakuş, Askeri; Altındağ, Serdar

    2011-01-01

    Woodworkers in the furniture industry are exposed to wood dust in their workplaces. The aim of this study is to investigate the effect of occupational wood dust exposure on the nasal mucociliary transport rates (NMTRs) in woodworkers. Twenty five woodworkers and 30 healthy controls were included in this study. Wood dust concentration in workplaces was measured using the sampling device. 99m Tc-macroaggregated albumin (99mTc-MAA) rhinoscintigraphy was performed, and NMTR was calculated in all cases. In statistical analysis, an independent samples t-test was used to compare NMTR of woodworkers and control subjects. We found that the mean NMTR of the woodworkers was lower than that of the healthy controls. However, there was not a statistically significant difference between them (P = 0.066). In conclusion, our findings suggested that wood dust exposure may not impair nasal mucociliary transport rate in woodworkers employed in joinery workshops. PMID:21804940

  6. Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to sup 99m Tc-DTPA

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

    Chinet, T.; Dusser, D.; Labrune, S.

    1990-02-01

    Respiratory epithelial clearance of {sup 99m}Tc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of {sup 113m}In-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stablemore » during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.« less

  7. Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis.

    PubMed

    Kennel, Stephen J; Stuckey, Alan; McWilliams-Koeppen, Helen P; Richey, Tina; Wall, Jonathan S

    2016-08-01

    Systemic peripheral amyloidosis is a rare disease in which misfolded proteins deposit in various organs. We have previously developed I-124 labeled peptide p5 + 14 as a tracer for positron emission tomography imaging of amyloid in patients. In this report, we now document the labeling efficiency, bioactivity, and stability of Tc-99m labeled p5 + 14 for single-photon emission computed tomography (SPECT) imaging of amyloidosis, validated in a mouse model of systemic amyloidosis. Radiochemical yield, purity, and biological activity of [(99m)Tc]p5 + 14 were documented by instant thin-layer chromatography (ITLC), SDS-PAGE and a quantitative amyloid fibril pulldown assay. The efficacy and stability were documented in serum amyloid protein A (AA) amyloid-bearing or wild-type (WT) control mice imaged with SPECT/X-ray computed tomography (CT) at two time points. The uptake and retention of [(99m)Tc]p5 + 14 in hepatosplenic amyloid was evaluated using region of interest (ROI) and tissue counting measurements. Tc-99m p5 + 14 was produced with a radiochemical yield of 75 % with greater than 90 % purity and biological activity comparable to that of radioiodinated peptide. AA amyloid was visualized by SPECT/CT imaging with specific uptake seen in amyloid-laden organs at levels ∼5 folds higher than in healthy mice. ROI analyses of decay-corrected SPECT/CT images showed <20 % loss of radiolabel from the 1 to 4 h imaging time points. Biodistribution data confirmed the specificity of the probe accumulation by amyloid-laden organs as compared to non-diseased tissues. [(99m)Tc]p5 + 14 is a specific and stable radiotracer for systemic amyloid in mice and may provide a convenient and inexpensive alternative to imaging of peripheral amyloidosis in patients.

  8. Synthesis, Characterization and Biological Studies of 99mTc and 188Re Peptides

    NASA Astrophysics Data System (ADS)

    Sanders, Vanessa

    Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed to label the pharmaceuticals for use in-vivo. Another radioisotope 188Re is also important due to its ability to be used for therapy while being tracked throughout the body. Radiotherapy gives radiopharmaceuticals a huge advantage by their ability to destroy rapidly growing cells. One of the main reasons there is interest in rhenium pharmaceuticals is the chemical similarity between it and technetium. The 188Re isotope also has a considerably short half-life of approximately 17 hours and has emission energy of 155 keV. The 188Re isotope is separated from 188W-188Re generator, analogously to the 99Mo-99mTc generator. The ligand used in this work is a pentapepetide macrocyclic ligand. This ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for imaging and therapeutic in vivo agents. Ligands are chosen based on their in-situ biological behavior, and are used in the complexation with technetium and rhenium. Understanding and exploiting technetium and rhenium chemistry can provide insight into the reaction mechanisms and coordination chemistry of these compounds. The exploration of various oxidation states as a function of the ligands used and the reaction conditions can help develop novel radiopharmaceuticals. The investigations of the manipulation of oxidation states

  9. 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.

  10. SPECT/CT with 99mTc-MAA in radioembolization with 90Y microspheres in patients with hepatocellular cancer.

    PubMed

    Hamami, Monia E; Poeppel, Thorsten D; Müller, Stephan; Heusner, Till; Bockisch, Andreas; Hilgard, Philipp; Antoch, Gerald

    2009-05-01

    Radioembolization with (90)Y microspheres is a novel treatment for hepatic tumors. Generally, hepatic arteriography and (99m)Tc-macroaggregated albumin (MAA) scanning are performed before selective internal radiation therapy to detect extrahepatic shunting to the lung or the gastrointestinal tract. Whereas previous studies have used only planar or SPECT scans, the present study used (99m)Tc-MAA SPECT/CT scintigraphy (SPECT with integrated low-dose CT) to evaluate whether SPECT/CT and additional diagnostic contrast-enhanced CT before radioembolization with (90)Y microspheres are superior to SPECT or planar imaging alone for detection of gastrointestinal shunting. In a prospective study, we enrolled 58 patients (mean age, 66 y; SD, 12 y; 10 women and 48 men) with hepatocellular carcinoma who underwent hepatic arteriography and scintigraphy with (99m)Tc-MAA using planar imaging, SPECT, and SPECT with integrated low-dose CT of the upper abdomen (acquired with a hybrid SPECT/CT camera). The ability of the different imaging modalities to detect extrahepatic MAA shunting was compared. Patient follow-up of a mean of 180 d served as the standard of reference. Gastrointestinal shunting was revealed by planar imaging in 4, by SPECT in 9, and by SPECT/CT in 16 of the 68 examinations. For planar imaging, the sensitivity for detection of gastrointestinal shunting was 25%, the specificity 87%, and the accuracy 72%. For SPECT without CT, the sensitivity was 56%, the specificity 87%, and the accuracy 79%. SPECT with CT fusion had a sensitivity of 100%, a specificity of 94%, and an accuracy of 96%. In 3 patients, MAA deposits in the portal vein could accurately be attributed to tumor thrombus only with additional information from contrast-enhanced CT. The follow-up did not show any gastrointestinal complications. SPECT with integrated low-dose CT using (99m)Tc-MAA is beneficial in radioembolization with (90)Y microspheres because it increases the sensitivity and specificity of (99m)Tc

  11. Feasibility and diagnostic performance of dual-tracer-guided sentinel lymph node biopsy in cT1-2N0M0 gastric cancer: a systematic review and meta-analysis of diagnostic studies.

    PubMed

    Huang, Ling; Wei, Tao; Chen, Junjun; Zhou, Donghui

    2017-05-16

    Dual-tracer-guided sentinel lymph node (SLN) biopsy may provide a promising diagnostic tool to assess accurately the status of lymph node metastasis in the surgical operation and assure the oncologic safety of the function or stomach preserving surgery. The diagnostic performance of this technology in recent studies varied. Thus, we conducted this meta-analysis. This systematic review and meta-analysis was registered at the PROSPERO. Eligible studies were searched in the PubMed, EMBASE, Web of Knowledge, and Cochrane Library databases. A random-effect model was used to pool the data. Summary receiver operator characteristic curves, analysis for publication bias, meta-regression, and subgroup analysis were also performed. The pooled SLN identification rate and sensitivity were 0.97 and 0.89. 99m Tc-human serum albumin with indocyanine green (ICG), 99m Tc-antimony sulfur colloid with ICG, performing SLN biopsy ≥15 min after dye injection, an SLN ≥5, the basin dissection, laparoscopic surgery, in studies conducted in Japan and studies published after 2012, were associated with higher sensitivity. CT1 stage, performing SLN biopsy ≥15 min after dye injection, in studies conducted in Japan and studies published after 2012, were related with a higher identification rate. Dual tracer is promising in SLN biopsy in gastric cancer, and the clinical application of SLN biopsy should be limited to the patients of cT1N0M0 gastric cancer. The combination of 99m Tc-human serum albumin and ICG as well as the combination of 99m Tc-antimony sulfur colloid and ICG may be the optimal tracer combination. However, it seems not justified to put this technique into routine clinical application recently. Some factors that might enhance diagnostic value are identified.

  12. Intraoperative gamma probe guidance with 99mTc-pertechnetate in the completion thyroidectomy.

    PubMed

    Aras, Gülseren; Gültekin, Salih Sinan; Küçük, Nuriye Ozlem; Demirer, Seher; Tuğ, Tuğbay

    2009-07-01

    Intraoperative gamma probe (GP) guidance with (99m)Tc-pertechnetate in the completion total thyroidectomy after a first thyroidectomy was investigated in this prospective study. The study group comprises of fourteen consecutive patients (14 females, age mean 50.2 +/- 12.0 years, age range 29-73 years). All patients underwent a second thyroidectomy due to inadequate (5/14 patients) and complementary (9/14 patients) interventions. Serum-free three iodothyronine, free thyroxin and thyroid stimulating hormone measurements, a neck ultrasonography (USG) and thyroid scintigraphy (TS) were performed in the preoperative and postoperative period. After a 185 MBq (5 mCi) injection of (99m)Tc-pertechnetate, background (BG), left thyroid lobe (LTL), right thyroid lobe (RTL) and pyramidal tyroid lobe (PTL) regions were counted in time before and after resection of thyroid remnants by intraoperative GP. All resection materials were evaluated by histopathologic examination. Preoperative TSH was less than 30 mIU/mL (mean 21 +/- 7) in all patients. Functioning thyroid remnants were shown in 13/14 patients on the preoperative TS and USG, which were diagnosed by USG in one but by TS in other one. We calculated that percentage median (minimum-maximum) values were 220.90% (56.00-411.11%) in LTL, 80.43% (11.54-471.05%) in RTL and 66.60% (-3.33 to 158.33%) in PTL for counts before resection, on the other hand, 15.96% (-20.55 to 47.62%) in LTL, 17.59% (-15.07 to 38.46%) in RTL and 17.59% (-1.96 to 57.14%) in PTL regions for counts after resection. There were statistically significant differences between these values belonging to before and after resection for LTL (p = 0.001), RTL (p = 0.001) and PTL (p = 0.008). Bilateral small foci in a patient and unilateral focus in other patient were observed in postoperative TS. Unilateral focus was detected on the RTL by GP, but not bilateral foci. Postoperative TSH levels increased to 30 mIU/mL (mean 69 +/- 26) at least. There was a statistically

  13. Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) Complexes for Targeting uPAR in Prostate Cancer.

    PubMed

    Kasten, Benjamin B; Ma, Xiaowei; Cheng, Kai; Bu, Lihong; Slocumb, Winston S; Hayes, Thomas R; Trabue, Steven; Cheng, Zhen; Benny, Paul D

    2016-01-20

    Developing new strategies to rapidly incorporate the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core into biological targeting vectors in radiopharmaceuticals continues to expand as molecules become more complex and as efforts to minimize nonspecific binding increase. This work examines a novel isothiocyanate-functionalized bifunctional chelate based on 2,2'-dipicolylamine (DPA) specifically designed for complexing the fac-[M(I)(CO)3](+) core. Two strategies (postlabeling and prelabeling) were explored using the isothiocyanate-functionalized DPA to determine the effectiveness of assembly on the overall yield and purity of the complex with amine containing biomolecules. A model amino acid (lysine) examined (1) amine conjugation of isothiocyanate-functionalized DPA followed by complexation with fac-[M(I)(CO)3](+) (postlabeling) and (2) complexation of fac-[M(I)(CO)3](+) with isothiocyanate-functionalized DPA followed by amine conjugation (prelabeling). Conducted with stable Re and radioactive (99m)Tc analogs, both strategies formed the product in good to excellent yields under macroscopic and radiotracer concentrations. A synthetic peptide (AE105) which targets an emerging biomarker in CaP prognosis, urokinase-type plasminogen activator receptor (uPAR), was also explored using the isothiocyanate-functionalized DPA strategy. In vitro PC-3 (uPAR+) cell uptake assays with the (99m)Tc-labeled peptide (8a) showed 4.2 ± 0.5% uptake at 4 h. In a murine model bearing PC-3 tumor xenografts, in vivo biodistribution of 8a led to favorable tumor uptake (3.7 ± 0.7% ID/g) at 4 h p.i. with relatively low accumulation (<2% ID/g) in normal organs not associated with normal peptide excretion. These results illustrate the promise of the isothiocyanate-functionalized approach for labeling amine containing biological targeting vectors with fac-[M(I)(CO)3](+).

  14. ECT imaging with Tc(V)-99m dimercaptosuccinic acid useful to detect lung metastases of osteosarcoma

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

    Ohta, H.; Ishii, M.; Yoshizumi, M.

    1985-01-01

    ECT imaging, using Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS) was performed in two patients with lung metastasis of osteosarcoma, and the results were compared with those of CT scan. Clear accumulation of Tc(V)-DMS was recognized in all cases in the same area that CT scans demonstrated. Tc(V)-DMS was labeled under optimal pH 8, had very low SnCl/sub 2/ concentrations, an equilibrium between a stable form and a dissociated form of anion TcO/sub 4/(3-) structurally similar to PO/sub 4/(3-), and was postulated for tumor uptake. Considering this proposed mechanism for Tc(V)-DMS uptake by tumor cells, ECT imaging using this tracer could be ofmore » use in the early detection of lung metastasis of osteosarcoma.« less

  15. Effect of different thickness of material filter on Tc-99m spectra and performance parameters of gamma camera

    NASA Astrophysics Data System (ADS)

    Nazifah, A.; Norhanna, S.; Shah, S. I.; Zakaria, A.

    2014-11-01

    This study aimed to investigate the effects of material filter technique on Tc-99m spectra and performance parameters of Philip ADAC forte dual head gamma camera. Thickness of material filter was selected on the basis of percentage attenuation of various gamma ray energies by different thicknesses of zinc material. A cylindrical source tank of NEMA single photon emission computed tomography (SPECT) Triple Line Source Phantom filled with water and Tc-99m radionuclide injected was used for spectra, uniformity and sensitivity measurements. Vinyl plastic tube was used as a line source for spatial resolution. Images for uniformity were reconstructed by filtered back projection method. Butterworth filter of order 5 and cut off frequency 0.35 cycles/cm was selected. Chang's attenuation correction method was applied by selecting 0.13/cm linear attenuation coefficient. Count rate was decreased with material filter from the compton region of Tc-99m energy spectrum, also from the photopeak region. Spatial resolution was improved. However, uniformity of tomographic image was equivocal, and system volume sensitivity was reduced by material filter. Material filter improved system's spatial resolution. Therefore, the technique may be used for phantom studies to improve the image quality.

  16. 99m Tc-HYNIC-(Ser)3 -J18 peptide: A radiotracer for non-small-cell lung cancer targeting.

    PubMed

    Shaghaghi, Zahra; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2018-02-14

    Radiolabeled peptide could be a useful tool for the diagnosis of non-small-cell lung cancer (NSCLC). In this study, HYNIC-(Ser) 3 -J18 peptide was labeled with 99m Tc using EDDA/tricine as coligands. The in vitro and in vivo studies of this radiolabeled peptide were performed for cellular-specific binding and tumor targeting in A-549 cells and tumor-bearing mice, respectively. The high radiochemical purity was obtained and this radiolabeled peptide exhibited high stability in buffer and serum. The radiolabeled peptide showed high affinity for the A-549 cells with a dissociation constant value (K D ) of 4.4 ± 0.8 nm. The tumor-muscles ratios were 2.7 and 4.4 at 1 and 2 hr after injection of 99m Tc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 in tumor-bearing mice. The tumor uptake was decreased after preinjection with non-labeled peptide for this radiolabeled peptide in blocking experiment. The results of this study showed the 99m Tc-(EDDA/tricine)-(Ser) 3 -HYNIC-J18 peptide might be a promising radiolabeled peptide for NSCLC targeting. © 2018 John Wiley & Sons A/S.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. [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.

  7. New method for the selective labeling of erythrocytes in whole blood with Tc-99m

    DOEpatents

    Srivastava, S.C.; Babich, J.W.; Straub, R.; Richards, P.

    1984-01-27

    Method and kit are described for the preparation of /sup 99m/Tc labeled red blood cells using whole blood in a closed sterile system containing stannous tin in a form such that it will enter the red blood cells and be available therein for the reduction of technetium.

  8. Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies Across Caco-2 Cells.

    PubMed

    Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

    2018-01-01

    Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and nonradioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In a non-radioactive study, ALD permeability was found to be 45 µg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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

  10. Tc-99m galactosyl-neoglycoalbumin: in vitro characterization of receptor-mediated binding

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

    Vera, D.R.; Krohn, K.A.; Stadalnik, R.C.

    1984-07-01

    Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. A characterization is made of the in vitro binding of Tc-99m galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to liver membrane. Structural modifications of NGA resulted in the alteration of the equilibrium constant, KA, and the forward-binding rate constant, kb. Binding was second-order; the relative amount of membrane-bound NGA depended on the initial concentrations of ligand and membrane. Membrane displacement studies, using carrier ligands in contrast to previously bound Tc-NGA or I-NGA, correlated with the binding characteristics of a native HBPmore » ligand, asialo-orosomucoid. Computer simulation was used to study the detectability of the changes in HBP concentration at different values of kb. The simulations indicated that radiopharmacokinetic sensitivity to alterations in (HBP) should be possible using a neoglycoalbumin preparation with a carbohydrate density within the range of 15 to 25 galactose units per albumin molecule.« less

  11. 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

  12. 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.

  13. [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.

  14. 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.

  15. Influence of bidentate ligand donor types on the formation and stability in 2 + 1 fac-[MI(CO)3]+ (M = Re, 99mTc) complexes.

    PubMed

    Hayes, Thomas R; Bottorff, Shalina C; Slocumb, Winston S; Barnes, Charles L; Clark, Aurora E; Benny, Paul D

    2017-01-24

    In the last two decades, a number of chelate strategies have been proposed for the fac-[M I (CO) 3 ] + (M = Re, 99m Tc) core in radiopharmaceutical applications. However, the development of new ligands/complexes with improved function and in vivo performance has been limited in recent years. Expanding on our previous studies using the 2 + 1 labeling strategy, a series of bidentate ligands (neutral vs. anionic) containing an aromatic amine in combination with monodentate pyridine analogs or imidazole were explored to determine the influence of the bidentate and monodentate ligands on the formation and stability of the respective complexes. The 2 + 1 complexes with Re and 99m Tc were synthesized in two steps and characterized by standard radio/chemical methods. X-ray characterization and density functional theory analysis of the Re 2 + 1 complexes with the complete bidentate series with 4-dimethylaminopyridine were conducted, indicating enhanced ligand binding energies of the neutral over anionic ligands. In the 99m Tc studies, anionic bidentate ligands had significantly higher formation yields of the 2 + 1 product, but neutral ligands appear to have increased stability in an amino acid challenge assay. Both bidentate series exhibited improved stability by increasing the basicity of the pyridine ligands.

  16. 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

  17. 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.

  18. Technetium tc 99m-labeled red blood cells in the preoperative diagnosis of cavernous hemangioma and other vascular orbital tumors.

    PubMed

    Polito, Ennio; Burroni, Luca; Pichierri, Patrizia; Loffredo, Antonio; Vattimo, Angelo G

    2005-12-01

    To evaluate technetium Tc 99m (99mTc) red blood cell scintigraphy as a diagnostic tool for orbital cavernous hemangioma and to differentiate between orbital masses on the basis of their vascularization. We performed 99mTc red blood cell scintigraphy on 23 patients (8 female and 15 male; mean age, 47 years) affected by an orbital mass previously revealed with computed tomography (CT) and magnetic resonance imaging (MRI) and suggesting cavernous hemangioma. In our diagnosis, we considered the orbital increase delayed uptake with the typical scintigraphic pattern known as perfusion blood pool mismatch. The patients underwent biopsy or surgical treatment with transconjunctival cryosurgical extraction when possible. Single-photon emission tomography (SPET) showed intense focal uptake in the orbit corresponding to radiologic findings in 11 patients who underwent surgical treatment and pathologic evaluation (9 cavernous hemangiomas, 1 hemangiopericytoma, and 1 lymphangioma). Clinical or histologic examination of the remaining 22 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the lacrimal gland, 1 astrocytoma, 1 ophthalmic vein thrombosis, and 1 orbital varix. The confirmation of the preoperative diagnosis by 99mTc red blood cell scintigraphy shows that this technique is a reliable tool for differentiating cavernous hemangiomas from other orbital masses (sensitivity, 100%; specificity, 86%) when ultrasound, CT, and MRI are not diagnostic. Unfortunately, 99mTc red blood cell scintigraphy results were positive in 1 patient with hemangiopericytoma and 1 patient with lymphangioma, which showed increased uptake in the lesion on SPET images because of the vascular nature of these tumors. Therefore, in these cases, the SPET images have to be integrated with data regarding clinical preoperative evaluation and CT scans or MRI studies. On the basis of our study, a complete diagnostic picture, CT scans or MRI studies, and

  19. Impact of Gate 99mTc DTPA GFR, Serum Creatinine and Urea in Diagnosis of Patients with Chronic Kidney Failure

    PubMed Central

    Miftari, Rame; Nura, Adem; Topçiu-Shufta, Valdete; Miftari, Valon; Murseli, Arbenita; Haxhibeqiri, Valdete

    2017-01-01

    Aim: The aim of this study was determination of validity of 99mTcDTPA estimation of GFR for early detection of chronic kidney failure Material and methods: There were 110 patients (54 males and 56 females) with kidney disease referred for evaluation of renal function at UCC of Kosovo. All patients were included in two groups. In the first group were included 30 patients confirmed with renal failure, whereas in the second group were included 80 patients with other renal disease. In study were included only patients with ready results of creatinine, urea and glucose in the blood serum. For estimation of GFR we have used the Gate GFR DTPA method. The statistical data processing was conducted using statistical methods such as arithmetic average, the student t-test, percentage or rate, sensitivity, specificity and accuracy of the test. Results: The average age of all patients was 36 years old. The average age of female was 37 whereas of male 35. Patients with renal failure was significantly older than patients with other renal disease (p<0.005). Renal failure was found in 30 patients (27.27%). The concentration of urea and creatinine in blood serum of patients with renal failure were significantly higher than in patients with other renal disease (P< 0.00001). GFR in patients with renal failure were significantly lower than in patients with other renal disease, 51.75 ml/min (p<0.00001). Sensitivity of uremia and creatininemia for detection of renal failure were 83.33%, whereas sensitivity of 99mTcDTPA GFR was 100%. Specificity of uraemia and creatininemia were 63% whereas specificity of 99mTcDTPA GFR was 47.5%. Diagnostic accuracy of blood urea and creatinine in detecting of renal failure were 69%, whereas diagnostic accuracy of 99mTcDTPA GFR was 61.8%. Conclusion: Gate 99mTc DTPA scintigraphy in collaboration with biochemical tests are very sensitive methods for early detection of patients with chronic renal failure. PMID:28883673

  20. Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

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

    Kawamura, J.; Hosakawa, S.; Yoshida, O.

    /sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

  1. Clickable, Hydrophilic Ligand for fac-[MI(CO)3]+ (M = Re/99mTc) Applied in an S-Functionalized α-MSH Peptide

    PubMed Central

    2015-01-01

    The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[MI(CO)3]+ (M = Re/99mTc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[99mTcI(CO)3]+ complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[ReI(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[99mTcI(OH2)3(CO)3]+. The corresponding 99mTc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[MI(CO)3]+ using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[MI(CO)3]+ complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR’s and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[MI(CO)3]+ using this synthetic route. The fac-[MI(CO)3]+-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the 99mTc

  2. 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.

  3. 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.

  4. Pattern of myocardial 99mTc-HMDP uptake and impact on myocardial function in patients with transthyretin cardiac amyloidosis.

    PubMed

    Pradel, Sarah; Brun, Stéphanie; Victor, Gérard; Pascal, Pierre; Fournier, Pauline; Ribes, David; Lavie-Badie, Yoan; Galinier, Michel; Carrié, Didier; Berry, Isabelle; Lairez, Olivier

    2018-06-07

    The purpose of the study was to describe the pattern of 99m Tc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA). Fifty patients with TTR-CA underwent 99m Tc- hydroxymethylene-diphosphonate ( 99m Tc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images. The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99m Tc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184). These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

  5. Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

    PubMed

    Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

    2015-08-01

    The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

  6. Kit preparation and biokinetics in women of 99mTc-EDDA/HYNIC-E-[c(RGDfK)]2 for breast cancer imaging.

    PubMed

    Ortiz-Arzate, Zareth; Santos-Cuevas, Clara L; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; García-Becerra, Rocío; Estrada, Gisela; Gómez-Argumosa, Edgar; Izquierdo-Sánchez, Vanessa

    2014-04-01

    In breast cancer, α(ν)β(3) and/or α(ν)β(5) integrins are overexpressed in both endothelial and tumour cells. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence are radiopharmaceuticals with high affinity and selectivity for these integrins. The RGD-dimer peptide (E-[c(RGDfK)]2) radiolabelled with (99m)Tc has been reported as a radiopharmaceutical with a 10-fold higher affinity for the α(ν)β(3) integrin compared with the RGD-monomer. Ethylenediamine-N,N'-diacetic acid (EDDA) is a hydrophilic molecule that may favour renal excretion when used as coligand in the (99m)Tc labelling of hydrazinonicotinamide (HYNIC) peptides and can easily be formulated in a lyophilized kit. The aim of this study was to establish a biokinetic model for (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 prepared from lyophilized kits and evaluate its dosimetry as a tumour-imaging agent in seven healthy women and three breast cancer patients. (99m)Tc labelling was performed by adding sodium pertechnetate solution and 0.2 mol/l phosphate buffer (pH 7.0) to a lyophilized formulation containing E-[c(RGDfK)]2, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated using reverse-phase high-performance liquid chromatography and instant thin-layer chromatography on silica gel analyses. Stability studies in human serum were carried out using size-exclusion high-performance liquid chromatography. In-vitro cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with blocked and nonblocked receptors. Biodistribution and tumour uptake were determined in MCF7 tumour-bearing nude mice with blocked and nonblocked receptors, and images were obtained using a micro-SPECT/PET/CT. Whole-body images from seven healthy women were acquired at 0.5, 1, 3, 6 and 24 h after (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 administration with radiochemical purities greater than 94%. Regions of interest were drawn around the source organs at each time frame. Each region of

  7. 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.

  8. 99mTc-HYNIC-TOC increased uptake can mimic malignancy in the pancreas uncinate process at somatostatin receptor SPECT/CT.

    PubMed

    Yamaga, Lilian Yuri Itaya; Neto, Guilherme Campos Carvalho; da Cunha, Marcelo Livorsi; Osawa, Akemi; Oliveira, Julio Cesar Silveira; Fonseca, Ricardo Quartim; Nogueira, Solange Amorim; Wagner, Jairo; Funari, Marcelo Gusmão

    2016-03-01

    The aim of this study was to assess the occurrence and frequency of increased physiologic uptake of 99mTc-HYNIC-TOC by the uncinate process of the pancreas in SPECT/CT images. Forty-six scans of 41 patients were evaluated retrospectively. The uptake of 99mTc-HYNIC-TOC was considered to be physiologic in patients with normal findings at dedicated abdominal CT or MR and lack of neoplastic lesions in clinical follow-ups. The intensity of uncinate process uptake was compared to the uptake of the normal liver. Focal uptake was attributed to the presence of pancreatic NET in 5 patients. Among the 36 patients without any evidence of malignancy in CT, MR and follow-up, 7 (19.4 %) showed increased uptake in the uncinate process. The intensity of uptake was lesser in 3 (8.3 %), similar in 3 and greater than the normal liver in 1 (2.8 %) case. Increased 99mTc-HYNIC-TOC uptake occurred in 19.4 % of those subjects without any evidence of neuroendocrine tumor in the uncinate process.

  9. 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 ...

  10. Scintigraphic imaging of Staphylococcus aureus infection using 99mTc radiolabeled aptamers.

    PubMed

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

    2017-10-01

    Staphylococcus aureus is a specie of great medical importance associated with many infections as bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device related infections. Early identification of infectious foci is crucial for successful treatment. Scintigraphy could contribute to this purpose since specific radiotracers were available. Aptamers due to their high specificity have great potential for radiopharmaceuticals development. In the present study scintigraphic images of S. aureus infectious foci were obtained using specific S. aureus aptamers radiolabeled with 99m Tc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Sentinel node detection in cervical cancer with (99m)Tc-phytate.

    PubMed

    Silva, Lucas B; Silva-Filho, Agnaldo L; Traiman, Paulo; Triginelli, Sérgio A; de Lima, Carla Flávia; Siqueira, Cristiano Ferrari; Barroso, Adelanir; Rossi, Telma Maria F F; Pedrosa, Moises Salgado; Miranda, Dairton; Melo, José Renan Cunha

    2005-05-01

    The aim of this study was to investigate the feasibility of sentinel lymph node (SLN) identification using radioisotopic lymphatic mapping with technetium-99 m-labeled phytate in patients undergoing radical hysterectomy with pelvic lymphadenectomy for treatment of early cervical cancer. Between July 2001 and February 2003, 56 patients with cervical cancer FIGO stage I (n = 53) or stage II (n = 3) underwent sentinel lymph node detection with preoperative lymphoscintigraphy ((99m)Tc-labeled phytate injected into the uterine cervix, at 3, 6, 9, and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and intraoperative lymphatic mapping with a handheld gamma probe. Radical hysterectomy was aborted in three cases because parametrial invasion was found intraoperatively and we performed only sentinel node resection. The remaining 53 patients underwent radical hysterectomy with complete pelvic lymphadenectomy. Sentinel nodes were detected using a handheld gamma-probe and removed for pathological assessment during the abdominal radical hysterectomy and pelvic lymphadenectomy. One or more sentinel nodes were detected in 52 out of 56 eligible patients (92.8%). A total of 120 SLNs were detected by lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively by gamma probe. Forty-four percent of SLNs were found in the external iliac area, 39% in the obturator region, 8.3% in interiliac region, and 6.7% in the common iliac area. Unilateral sentinel nodes were found in thirty-one patients (59%). The remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal metastases were confirmed in 17 (32%) cases. In 10 of these patients, only SLNs had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin were submitted to cytokeratin immunohistochemical analysis. Five (5.1%) micrometastases were identified with this technique. The sensitivity of the sentinel node was 82.3% (CI 95% = 56.6-96.2) and the negative predictive value was 92

  12. Influence of Bidentate Ligand Donor Types on the Formation and Stability in 2+1 fac-[MI(CO)3]+ (M = Re, 99mTc) Complexes

    PubMed Central

    Hayes, Thomas R.; Bottorff, Shalina C.; Slocumb, Winston S.; Barnes, Charles L.; Clark, Aurora E.; Benny, Paul D.

    2017-01-01

    In the last two decades, a number of chelate strategies have been proposed for the fac-[MI(CO)3]+ (M = Re, 99mTc) core in radiopharmaceutical applications. However, the development of new ligands/complexes with improved function and in vivo performance has been limited in recent years. Expanding on our previous studies using the 2+1 labeling strategy, a series of bidentate ligands (neutral vs. anionic) containing an aromatic amine in combination with monodentate pyridine analogs or imidazole were explored to determine the influence of the bidentate and monodentate ligands on the formation and stability of the respective complexes. The 2+1 complexes with Re and 99mTc were synthesized in two steps and characterized by standard radio/chemical methods. X-ray characterization and density functional theory analysis of the Re 2+1 complexes with the complete bidentate series with 4-dimethylaminopyridine were conducted, indicating enhanced ligand binding energies of the neutral over anionic ligands. In the 99mTc studies, anionic bidentate ligands had significantly higher formation yields of the 2+1 product, but neutral ligands appear to have increased stability in an amino acid challenge assay. Both bidentate series exhibited improved stability by increasing the basicity of the pyridine ligands. PMID:28045466

  13. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses.

    PubMed

    Bokhari, Sabahat; Castaño, Adam; Pozniakoff, Ted; Deslisle, Susan; Latif, Farhana; Maurer, Mathew S

    2013-03-01

    Differentiating immunoglobulin light-chain (AL) from transthyretin-related cardiac amyloidoses (ATTR) is imperative given implications for prognosis, therapy, and genetic counseling. We validated the discriminatory ability of (99m)Tc-pyrophosphate ((99m)Tc-PYP) scintigraphy in AL versus ATTR. Forty-five subjects (12 AL, 16 ATTR wild type, and 17 ATTR mutants) underwent (99m)Tc-PYP planar and single-photon positive emission computed tomography cardiac imaging. Scans were performed by experienced nuclear cardiologists blinded to the subjects' cohort assignment. Cardiac retention was assessed with both a semiquantitative visual score (range, 0; no uptake to 3, diffuse uptake) and by quantitative analysis by drawing a region of interest over the heart corrected for contralateral counts and calculating a heart-to-contralateral ratio. Subjects with ATTR cardiac amyloid had a significantly higher semiquantitative cardiac visual score than the AL cohort (2.9±0.06 versus 0.8±0.27; P<0.0001) as well as a higher quantitative score (1.80±0.04 versus 1.21±0.04; P<0.0001). Using a heart-to-contralateral ratio >1.5 consistent with intensely diffuse myocardial tracer retention had a 97% sensitivity and 100% specificity with area under the curve 0.992, P<0.0001 for identifying ATTR cardiac amyloidosis. (99m)Tc-PYP cardiac imaging distinguishes AL from ATTR cardiac amyloidosis and may be a simple, widely available method for identifying subjects with ATTR cardiac amyloidosis, which should be studied in a larger prospective manner.

  14. 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

  15. 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.

  16. 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

  17. Detection of breast cancer microcalcification using (99m)Tc-MDP SPECT or Osteosense 750EX FMT imaging.

    PubMed

    Felix, Dayo D; Gore, John C; Yankeelov, Thomas E; Peterson, Todd E; Barnes, Stephanie; Whisenant, Jennifer; Weis, Jared; Shoukouhi, Sepideh; Virostko, John; Nickels, Michael; McIntyre, J Oliver; Sanders, Melinda; Abramson, Vandana; Tantawy, Mohammed N

    2015-03-01

    In previous work, we demonstrated the presence of hydroxyapetite (type II microcalcification), HAP, in triple negative MDA-MB-231 breast cancer cells. We used (18)F-NaF to detect these types of cancers in mouse models as the free fluorine, (18)F(-), binds to HAP similar to bone uptake. In this work, we investigate other bone targeting agents and techniques including (99m)Tc-MDP SPECT and Osteosense 750EX FMT imaging as alternatives for breast cancer diagnosis via targeting HAP within the tumor microenvironment. Thirteen mice were injected subcutaneously in the right flank with 10(6) MDA-MB-231 cells. When the tumor size reached ~0.6 cm(3), mice (n=9) were injected with ~37 MBq of (99m)Tc-MDP intravenously and then imaged one hour later in a NanoSPECT/CT or injected intravenously with 4 nmol/g of Osetosense 750EX and imaged 24 hours later in an FMT (n=4). The imaging probe concentration in the tumor was compared to that of muscle. Following SPECT imaging, the tumors were harvested, sectioned into 10 μm slices, and underwent autoradiography or von Kossa staining to correlate (99m)Tc-MDP binding with HAP distribution within the tumor. The SPECT images were normalized to the injected dose and regions-of-interest (ROIs) were drawn around bone, tumor, and muscle to obtain the radiotracer concentration in these regions in units of percent injected dose per unit volume. ROIs were drawn around bone and tumor in the FMT images as no FMT signal was observed in normal muscle. Uptake of (99m)Tc-MDP was observed in the bone and tumor with little or no uptake in the muscle with concentrations of 11.34±1.46 (mean±SD), 2.22±0.95, and 0.05±0.04%ID/cc, respectively. Uptake of Osteosense 750EX was also observed in the bone and tumor with concentrations of 0.35±0.07 (mean±SD) and 0.04±0.01picomoles, respectively. No FMT signal was observed in the normal muscle. There was no significant difference in the bone-to-tumor ratio between the two modalities (5.1±2.3 for SPECT and 8.8

  18. Theoretical Modeling of 99 Tc NMR Chemical Shifts

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

    Hall, Gabriel B.; Andersen, Amity; Washton, Nancy M.

    Technetium (Tc) displays a rich chemistry due to the wide range of oxidation states (from -I to +VII) and ability to form coordination compounds. Determination of Tc speciation in complex mixtures is a major challenge, and 99Tc NMR spec-troscopy is widely used to probe chemical environments of Tc in odd oxidation states. However interpretation of the 99Tc NMR data is hindered by the lack of reference compounds. DFT computations can help fill this gap, but to date few com-putational studies have focused on 99Tc NMR of compounds and complexes. This work systematically evaluates the inclu-sion small percentages of Hartree-Fock exchangemore » correlation and relativistic effects in DFT computations to support in-terpretation of the 99Tc NMR spectra. Hybrid functionals are found to perform better than their pure GGA counterparts, and non-relativistic calculations have been found to generally show a lower mean absolute deviation from experiment. Overall non-relativistic PBE0 and B3PW91 calculations are found to most accurately predict 99Tc NMR chemical shifts.« less

  19. Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

    PubMed

    Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

    2014-02-17

    Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.

  20. 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.

  1. 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

  2. Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience.

    PubMed

    Kapoor, Seema; Ratan, Simmi K; Kashyap, Ravi; Mittal, S K; Rajeshwari, K; Rawat, H; Verma, Jyoti

    2002-09-01

    To evaluate protien using enteropathy by Tc-99m dextran scintigraphy. Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of alpha-1 antitrypsin in stools and by endoscopic biopsy. The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE. The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.

  3. Re-Search for Extinct 99Tc and 98Tc in the Early Solar System

    NASA Astrophysics Data System (ADS)

    Yin, Q.; Jagoutz, E.; Wanke, H.

    1992-07-01

    .89+- 0.24epsilon) of the ^99Ru/^101Ru ratio from the terrestrial mean is observed, a first indication that ^99Tc was alive in the early solar system. With the production ratio of ^99Tc/^99Ru=0.75 (Kappeler et al., 1989), a 2.9+-0.2 m.y. time interval (delta) between the nucleosynthetic process and formation of Maralinga is calculated, assuming there is no significant Tc/Ru fractionation since their production. This time interval is consistent with delta>=1.8 m.y. set by ^41Ca (tau(sub)1/2=1.03x10^5 yr) result (Hutcheon et al., 1984) and delta<=~3 m.y. inferred from ^26Al (tau(sub)1/2=7.16x10^5 yr) result (Lee et al., 1977), and gives the most stringent control on delta for the related nucleosynthetic process. The ^99Ru/^101Ru ratio in Gibeon is within error of the laboratory standard value. Since the nucleosynthetic origins of ^107Pd and ^99Tc are similar, the absence of ^99Ru anomaly (^99Ru*) and the presence of ^107Ag* in Gibeon (Chen and Wasserburg, 1990) indicate that core-mantle differentiation in the parent body of Gibeon happened between 2 and 10 m.y. after the nucleosynthetic sources produced these two parent nuclides. In this time span ^26Al was still alive and thus supports the model of ^26Al being a heat source for early planetary differentiation. Chen, J. H. and Wasserburg, G. J. , Geochim. Cosmochim. Acta. (1990) 54, 1729-1743. Creaser, R. A., Papanastassiou, D. A. and Wasserburg, G. J. (1991) Geochim. Cosmochim. Acta. 55, 397-401. Herr, W., Merz, E., Eberhardt, P., Geiss, J., Lang, C. and Signer, P. (1958) Geochim. Cosmochim. Acta. 14, 158. Hutcheon, I. D., Armstrong, J. T., and Wasserburg, G. J. (1984) LPSC XV, 387-388 (abstract). Kappeler, F., Beer, H., and Wisshak, K. (1989) Rep. Prog. Phys. 52. 945-1013. Lee, T., Papanastassiou, D. A. and Wasserburg, G. J. (1977) Astrophys. J. (Letters) 211, L107-L110. Smith, V. V. and Lambert, D. L. (1988)t. Astrophys. J., 333, 219- 226.

  4. 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

  5. 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

  6. Novel Index (Hepatic Receptor: IHR) to Evaluate Hepatic Functional Reserve Using (99m)Tc-GSA Scintigraphy.

    PubMed

    Hasegawa, Daisuke; Onishi, Hideo; Matsutomo, Norikazu

    2016-02-01

    This study aimed to evaluate the novel index of hepatic receptor (IHR) on the regression analysis derived from time activity curve of the liver for hepatic functional reserve. Sixty patients had undergone (99m)Tc-galactosyl serum albumin ((99m)Tc-GSA) scintigraphy in the retrospective clinical study. Time activity curves for liver were obtained by region of interest (ROI) on the whole liver. A novel hepatic functional predictor was calculated with multiple regression analysis of time activity curves. In the multiple regression function, the objective variables were the indocyanine green (ICG) retention rate at 15 min, and the explanatory variables were the liver counts in 3-min intervals until end from beginning. Then, this result was defined by IHR, and we analyzed the correlation between IHR and ICG, uptake ratio of the heart at 15 minutes to that at 3 minutes (HH15), uptake ratio of the liver to the liver plus heart at 15 minutes (LHL15), and index of convexity (IOC). Regression function of IHR was derived as follows: IHR=0.025×L(6)-0.052×L(12)+0.027×L(27). The multiple regression analysis indicated that liver counts at 6 min, 12 min, and 27 min were significantly related to objective variables. The correlation coefficient between IHR and ICG was 0.774, and the correlation coefficient between ICG and conventional indices (HH15, LHL15, and IOC) were 0.837, 0.773, and 0.793, respectively. IHR had good correlation with HH15, LHL15, and IOC. The finding results suggested that IHR would provide clinical benefit for hepatic functional assessment in the (99m)Tc-GSA scintigraphy.

  7. KEY COMPARISON Update of the BIPM.RI(II)-K1.Tc-99m comparison of activity measurements for the radionuclide 99mTc to include new results for the LNE-LNHB and the NPL

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Courte, S.; Ratel, G.; Moune, M.; Johansson, L.; Keightley, J.

    2010-01-01

    In 2007 and 2008 respectively, the Laboratoire national de métrologie et d'essais-Laboratoire national Henri Becquerel (LNE-LNHB), France and the National Physical Laboratory (NPL), UK, submitted ampoules with between 10 MBq and 130 MBq activity of 99mTc to the International Reference System (SIR), to update their results in the BIPM.RI(II)-K1.Tc-99m comparison. Together with the four other national metrology institutes (NMI) that are participants, thirteen samples have been submitted since 1983. The key comparison reference value (KCRV) has been recalculated to include the latest primary results of the PTB and the LNE-LNHB as this makes the evaluation more robust. The degrees of equivalence between each equivalent activity measured in the SIR are given in the form of a matrix for all six NMIs. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  8. 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

  9. 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

  10. 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

  11. 99mTc-EDDA/HYNIC-TOC and (18)F-FDG in thyroid cancer patients with negative (131)I whole-body scans.

    PubMed

    Gabriel, Michael; Froehlich, Franz; Decristoforo, Clemens; Ensinger, Christian; Donnemiller, Eveline; von Guggenberg, Elisabeth; Heute, Dirk; Moncayo, Roy

    2004-03-01

    Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22-90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A ( n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B ( n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive (99m)Tc-TOC findings was positively correlated ( P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with (18)F-FDG PET ( P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohen's kappa of 0.62 (0.47-0.78)]. In conclusion, scintigraphy with (99m)Tc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.

  12. Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

    PubMed

    Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

    1995-05-01

    Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

  13. /sup 99m/Tc-IDA hepatobiliary imaging following upper abdominal surgery. [IDA = acetanilide iminodiacetic acid

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

    Rosenthall, L.; Fonseca, C.; Arzoumanian, A.

    1979-03-01

    Bile flow patterns were studied with serial /sup 99m/Tc-IDA images in 19 patients with cholecysto- and choledochointestinal anastomoses, gastroenteric bypasses, and combinations of the two. Complications such as anastomotic, afferent, and efferent loop obstruction and bile leakage were readily detected even in the presence of jaundice. This noninvasive technique warrants further investigation to determine its indications and weaknesses.

  14. Radionuclide imaging in herpes simplex encephalitis. [/sup 99m/Tc tracer techniques

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

    Karlin, C.A.; Robinson, R.G.; Hinthorn, D.R.

    1978-01-01

    Eight patients with herpes simplex encephalitis among the 10 cases diagnosed at the University of Kansas Medical Center from 1966 to 1976 were studied with /sup 99m/Tc early in their diagnostic work-up. The images were unilaterally positive in the temporal lobe area in all 8 patients. Radionuclide studies can suggest herpes simplex as the specific etiology in cases of encephalitis and can also indicate the best site for brain biopsy to confirm the diagnosis by fluorescent antibody techniques. Appropriate antiviral therapy should be instituted as soon as possible to alter the course of this destructive form of viral encephalitis.

  15. 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.

  16. Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

    PubMed

    Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Rodriguez-Cortés, Jeanette; Pedraza-López, Martha; Ramírez-Iglesias, María Teresa

    2006-04-01

    Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours. To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours. HYNIC was conjugated to the epsilon-amino group of Lys 3 residue at the N-terminal region of bombesin via succinimidyl-N-Boc-HYNIC at pH 9.0. 99mTc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer pH 7.0 to a lyophilized formulation. Stability studies were carried out by reversed phase HPLC and ITLC-SG analyses in serum and cysteine solutions. In-vitro internalization was tested using human prostate cancer PC-3 cells with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in PC-3 tumour-bearing nude mice. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin was obtained with radiochemical purities >93% and high specific activity ( approximately 0.1 GBq.nmol). Results of in-vitro studies demonstrated a high stability in serum and cysteine solutions, specific cell receptor binding and rapid internalization. Biodistribution data showed a rapid blood clearance, with predominantly renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas and PC-3 tumours. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin obtained from lyophilized kit formulations has promising characteristics for the diagnosis of malignant tumours that over-express the GRP receptor.

  17. Comparison of different methods for radiochemical purity testing of [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide.

    PubMed

    von Guggenberg, Elisabeth; Penz, Barbara; Kemmler, Georg; Virgolini, Irene; Decristoforo, Clemens

    2006-02-01

    [99mTc-EDDA-HYNIC-D-Phe1,Tyr3]-octreotide (99mTc-EDDA-HYNIC-TOC) is an alternative radioligand for somatostatin receptor (SSTR) scintigraphy of neuroendocrine tumours. In order to allow a rapid and accurate determination of the quality in the clinical routine the aim of this study was to evaluate different methods of radiochemical purity (RCP) testing. Three different methods of RCP testing were compared: high-performance liquid chromatography (HPLC), thin layer chromatography (TLC) and minicolumn (Sep-Pak purification = SPE). HPLC was shown to be the most effective method for the quality control. The use of TLC and SPE is only recommended after sufficient practical labelling experience.

  18. 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.

  19. Comparison of 99mTc-MDP SPECT qualitative vs quantitative results in patients with suspected condylar hyperplasia.

    PubMed

    López Buitrago, D F; Ruiz Botero, J; Corral, C M; Carmona, A R; Sabogal, A

    To compare qualitative vs quantitative results of Single Photon Emission Computerised Tomography (SPECT), calculated from percentage of 99m Tc-MDP (methylene diphosphonate) uptake, in condyles of patients with a presumptive clinical diagnosis of condylar hyperplasia. A retrospective, descriptive study was conducted on the 99m Tc-MDP SPECT bone scintigraphy reports from 51 patients, with clinical impression of facial asymmetry related to condylar hyperplasia referred by their specialist in orthodontics or maxillofacial surgery, to a nuclear medicine department in order to take this type of test. Quantitative data from 99m Tc-MDP condylar uptake of each were obtained and compared with qualitative image interpretation reported by a nuclear medicine expert. The concordances between the 51 qualitative and quantitative reports results was established. The total sample included 32 women (63%) and 19 men (37%). The patient age range was 13-45 years (21±8 years). According to qualitative reports, 19 patients were positive for right side condylar hyperplasia, 12 for left side condylar hyperplasia, with 8 bilateral, and 12 negative. The quantitative reports diagnosed 16 positives for right side condylar hyperplasia, 10 for left side condylar hyperplasia, and 25 negatives. Nuclear medicine images are an important diagnostic tool, but the qualitative interpretation of the images is not as reliable as the quantitative calculation. The agreement between the two types of report is low (39.2%, Kappa=0.13; P>.2). The main limitation of quantitative reports is that they do not register bilateral condylar hyperplasia cases. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  20. 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

  1. [Sentinel node detection in early stage of cervical carcinoma using 99mTc-nanocolloid and blue dye].

    PubMed

    Sevcík, L; Klát, J; Gráf, P; Koliba, P; Curík, R; Kraft, O

    2007-04-01

    The aim of the study was to analyse the feasibility of intraoperative sentinel lymph nodes (SLN) detection using gamma detection probe and blue dye in patients undergoing radical hysterectomy for treatment of early stage of cervical cancer. Prospective case observational study. In the period from May 2004 to February 2006 77 patients with early stage of cervical cancer who underwent a radical surgery were included into the study. Patients were divided into three groups according to the tumour volume. First group consists of patients FIGO IA2 and FIGO IB1 with tumour diameter less than 2 cm, second group tumours FIGO IB1 with tumour diameter more than 2 cm and third group stadium IB2. SLN was detected by blue dye and Tc99. Preoperative lymphoscintigraphy was done after Tc99 colloid injection, intraoperative detection was performed by visual observation and by hand-held gamma-detection probe. SLN were histologically and immunohistochemically analysed. A total number of 2764 lymph nodes with an average 36 and 202 SLN with an average 2.6 were identified. The SLN detection rate was 94.8% per patient and 85.1% for the side of dissection and depends on the tumor volume. SLN were identified in obturator area in 48%, in external iliac area in 15%, in common iliac and internal iliac both in 9%, in interiliac region in 8%, in praesacral region in 6% and in parametrial area in 5%. Metastatic disease was detected in 31 patients (40.2%), metastatic involvement of SLN only in 12 patients (15.6%). False negative rate was 2.6%, sensitivity and negative predictive value calculated by patient were 923% and 95.7%. Intraoperative lymphatic mapping using combination of technecium-99-labeled nanocolloid and blue dye are feasible, safe and accurate techniques to identified SLN in early stage of cervical cancer.

  2. Kit for the rapid preparation of .sup.99m Tc red blood cells

    DOEpatents

    Richards, Powell; Smith, Terry D.

    1976-01-01

    A method and sample kit for the preparation of .sup.99m Tc-labeled red blood cells in a closed, sterile system. A partially evacuated tube, containing a freeze-dried stannous citrate formulation with heparin as an anticoagulant, allows whole blood to be automatically drawn from the patient. The radioisotope is added at the end of the labeling sequence to minimize operator exposure. Consistent 97% yields in 20 minutes are obtained with small blood samples. Freeze-dried kits have remained stable after five months.

  3. 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.

  4. Coordination modes of multidentate ligands in fac-[Re(CO)(3)(polyaminocarboxylate)] analogues of (99m)Tc radiopharmaceuticals. dependence on aqueous solution reaction conditions.

    PubMed

    Lipowska, Malgorzata; He, Haiyang; Xu, Xiaolong; Taylor, Andrew T; Marzilli, Patricia A; Marzilli, Luigi G

    2010-04-05

    We study Re analogues of (99m)Tc renal agents to interpret previous results at the (99m)Tc tracer level. The relative propensities of amine donors versus carboxylate oxygen donors of four L = polyaminocarboxylate ligands to coordinate in fac-[Re(I)(CO)(3)L](n) complexes were assessed by examining the reaction of fac-[Re(I)(CO)(3)(H(2)O)(3)](+) under conditions differing in acidity and temperature. All four L [N,N-bis-(2-aminoethyl)glycine (DTGH), N,N-ethylenediaminediacetic acid, diethylenetriamine-N-malonic acid, and diethylenetriamine-N-acetic acid] can coordinate as tridentate ligands while creating a dangling chain terminated in a carboxyl group. Dangling carboxyl groups facilitate renal clearance in fac-[(99m)Tc(I)(CO)(3)L](n) agents. Under neutral conditions, the four ligands each gave two fac-[Re(I)(CO)(3)L](n) products with HPLC traces correlating well with known traces of the fac-[(99m)Tc(I)(CO)(3)L](n) mixtures. Such mixtures are common in renal agents because the needed dangling carboxyl group can compete for a coordination site. However, the HPLC separations needed to assess the biodistribution of a single tracer are impractical in a clinical setting. One goal in investigating this Re chemistry is to identify conditions for avoiding this problem of mixtures in preparations of fac-[(99m)Tc(I)(CO)(3)L](n) renal tracers. After separation and isolation of the fac-[Re(I)(CO)(3)L](n) products, NMR analysis of all products and single crystal X-ray crystallographic analysis of both DTGH products, as well as one product each from the other L, allowed us to establish coordination mode unambiguously. The product favored in acidic conditions has a dangling amine chain and more bound oxygen. The product favored in basic conditions has a dangling carboxyl chain and more bound nitrogen. At the elevated temperatures used for simulating tracer preparation, equilibration was facile (ca. 1 h or less), allowing selective formation of one product by utilizing acidic or

  5. Synthesis, Characterization, and In Vitro Evaluation of New (99m)Tc/Re(V)-Cyclized Octreotide Analogues: An Experimental and Computational Approach.

    PubMed

    Li, Yawen; Ma, Lixin; Gaddam, Vikram; Gallazzi, Fabio; Hennkens, Heather M; Harmata, Michael; Lewis, Michael R; Deakyne, Carol A; Jurisson, Silvia S

    2016-02-01

    Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing (186)Re- and (188)Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe(1)-Cys(2)-Tyr(3)-DTrp(4)-Lys(5)-Thr(6)-Cys(7)-Thr(OH)(8) (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO](3+) core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys(2) in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr(3) in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO](3+) core. The re-cyclization reaction was translated to the (99m)Tc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total (99m)Tc labeling yield was achieved by ligand exchange from (99m)Tc-glucoheptonate at 60 °C for an hour. About 100% and 51% of (99m)Tc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.

  6. Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients.

    PubMed

    Hsiao, Ing-Tsung; Weng, Yi-Hsin; Lin, Wey-Yil; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Kung, Mei-Ping; Lu, Chin-Song; Lin, Kun-Ju

    2014-04-01

    (99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects. Eighteen subjects (8 HC and 10 PD) were recruited for (99m)Tc-TRODAT-1 SPECT, (18)F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts-1). The nonparametric Mann-Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities. The SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p<0.001), and showed significant different between HC and PD subjects. Of note, the (18)F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to (99m)Tc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from (18)F-AV-133 image as compared to (99m)Tc-TRODAT-1 especially at the substantia nigra region. (18)F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical

  7. Breast tumor targeting with (99m)Tc-HYNIC-PR81 complex as a new biologic radiopharmaceutical.

    PubMed

    Salouti, Mojtaba; Rajabi, Hossein; Babaei, Mohammad Hossein; Rasaee, Mohammad Javad

    2008-10-01

    Human epithelial mucin, MUC1, is commonly overexpressed in adenocarcinoma that includes more than 80% of breast cancers. The PR81 is a murine anti-MUC1 monoclonal antibody (MAb) that was prepared against the human breast cancer. We developed an indirect method for labeling of this antibody with (99m)Tc in order to use the new preparation in immunoscintigraphy studies of BALB/c mice bearing breast tumors. The (99m)Tc-PR81 complex was prepared using the HYNIC as a chelator and tricine as a coligand. The labeling efficiency determined by instant thin-layer chromatography (ITLC) was 89.2%+/-4.7%, and radiocolloides measured by cellulose nitrate electrophoresis were 3.4%+/-0.9%. The in vitro stability of labeled product was determined at room temperature by ITLC and in human serum by gel filtration chromatography - 88.3%+/-4.6% and 79.8%+/-5.7% over 24 h, respectively. The integrity of labeled MAb was checked by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis, and no significant fragmentation was seen. The results of cell binding studies showed that both labeled and unlabeled PR81 were able to compete for binding to MCF 7 cells. Biodistribution studies performed in female BALB/c mice with breast tumor xenografts at 4, 16 and 24 h after the (99m)Tc-HYNIC-PR81 injection demonstrated a specific localization of the compound at the site of tumors and minimum accumulation in non target organs. The tumor imaging was performed in BALB/c mice with breast xenograft tumors at 4, 8, 12, 16, 20, 24, 28, 32 and 36 h after the complex injection. The tumors were visualized with high sensitivity after 8 h. The findings showed that the new radiopharmaceutical is a promising candidate for radioimmunoscintigraphy of the human breast cancer.

  8. Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study.

    PubMed

    Plachcinska, Anna; Mikolajczak, Renata; Maecke, Helmut; Mlodkowska, Ewa; Kunert-Radek, Jolanta; Michalski, Andrzej; Rzeszutek, Katarzyna; Kozak, Jozek; Kusmierek, Jacek

    2004-04-01

    The clinical usefulness of a new 99mTc-labeled somatostatin analogue has been studied from the standpoint of oncological diagnostics. The group of patients studied included 40 individuals with diagnosed malignant neoplasms (32 primary and 8 metastatic). Among the primary tumors were 7 pituitary adenomas (5 hormonally active and 2 inactive), 1 liposarcoma, 2 carcinoids, 1 breast carcinoma, and 21 cases of lung cancer (2 small cell and 19 non-small cell) were represented. The metastatic tumors consisted of: 3 malignant melanomas, 1 pheochromocytoma, 1 prostatic cancer, 1 leiomyosarcoma, 1 pancreatic carcinoma ectopically secreting ACTH, and 1 carcinoid of the thymus. The radiopharmaceutical, 99mTc-EDDA/HYNIC-octreotide, was i.v. administered at the activity of 740-925 MBq. The imaging was comprized of a whole-body scan and single photon emission computed tomography. Positive scintigrams were obtained in 4 of 5 hormonally active pituitary adenomas, in 1 of 2 cases of carcinoid, in liposarcoma, breast cancer, and all cases of small cell (SCLC) and non-small cell lung cancer (NSCLC). The neoplastic metastases were visualized in 2 of 3 cases of melanoma and in patients with pheochromocytoma, pancreatic carcinoma secreting ACTH, and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, leiomyosarcoma, and in cases of metastasis from the prostatic carcinomas. The results of this pilot study indicated that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for the imaging of a wide range of primary and metastatic tumors. More detailed indications for the clinical usefulness of the new tracer for the imaging of selected tumor types require studies on much larger groups of patients. Special attention should be paid to the successful imaging of all cases of NSCLC.

  9. Clinical application of 99mTc-HYNIC-TOC SPECT/CT in diagnosing and monitoring of pancreatic neuroendocrine neoplasms.

    PubMed

    Xu, Junyan; Li, Yi; Xu, Xiaoping; Zhang, Jiangang; Zhang, Yingjian; Yu, Xianjun; Huang, Dan

    2018-06-20

    Our aim of this research was to determine the value of SPECT/CT with 99m Tc-HYNIC-TOC for evaluation of the pancreatic masses which were suspected as neuroendocrine neoplasms and follow-up of patients with pancreatic neuroendocrine neoplasms. We retrospectively analyzed 184 patients who performed 99m Tc-HYNIC-TOC SPECT/CT. All the patients were divided into two groups: one for assessment of diagnostic efficiency for pancreatic suspected masses (n = 140) and another for monitoring recurrence after surgery (n = 44). The image findings acquired at 2 h postinjection were compared to final diagnoses from pathological results and clinical follow-up. Then, the correlation between ratios of tumor-to-background (TBR) and tumor grade was analyzed. In group 1, 95/140 (67.9%) patients were confirmed as neuroendocrine neoplasms including 85 neuroendocrine tumors and 10 neuroendocrine carcinomas. Patient-based analysis showed that the sensitivity, specificity and accuracy of diagnosing neuroendocrine neoplasms with SPECT/CT were 81.1, 84.4 and 82.1%. There was significant difference of TBRs among G1, G2 and G3 (F = 3.175, P = 0.048). In group 2, 22/44 (50.0%) patients occurred metastasis mainly in liver. The sensitivity, specificity and accuracy of monitoring recurrence were 87.0, 100 and 93.2%. 99m Tc-HYNIC-TOC SPECT/CT is a reliable method of diagnosing and monitoring of pancreatic neuroendocrine neoplasms, especially neuroendocrine tumors.

  10. Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules.

    PubMed

    Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-11-07

    [ 99m Tc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

  11. 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.

  12. 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.

  13. 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.

  14. (99m)Tc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials.

    PubMed

    Belhocine, Tarik Z; Blankenberg, Francis G; Kartachova, Marina S; Stitt, Larry W; Vanderheyden, Jean-Luc; Hoebers, Frank J P; Van de Wiele, Christophe

    2015-12-01

    (99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in

  15. Use of quantitative SPECT/CT reconstruction in 99mTc-sestamibi imaging of patients with renal masses.

    PubMed

    Jones, Krystyna M; Solnes, Lilja B; Rowe, Steven P; Gorin, Michael A; Sheikhbahaei, Sara; Fung, George; Frey, Eric C; Allaf, Mohamad E; Du, Yong; Javadi, Mehrbod S

    2018-02-01

    Technetium-99m ( 99m Tc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has previously been shown to allow for the accurate differentiation of benign renal oncocytomas and hybrid oncocytic/chromophobe tumors (HOCTs) apart from other malignant renal tumor histologies, with oncocytomas/HOCTs showing high uptake and renal cell carcinoma (RCC) showing low uptake based on uptake ratios from non-quantitative single-photon emission computed tomography (SPECT) reconstructions. However, in this study, several tumors fell close to the uptake ratio cutoff, likely due to limitations in conventional SPECT/CT reconstruction methods. We hypothesized that application of quantitative SPECT/CT (QSPECT) reconstruction methods developed by our group would provide more robust separation of hot and cold lesions, serving as an imaging framework on which quantitative biomarkers can be validated for evaluation of renal masses with 99m Tc-sestamibi. Single-photon emission computed tomography data were reconstructed using the clinical Flash 3D reconstruction and QSPECT methods. Two blinded readers then characterized each tumor as hot or cold. Semi-quantitative uptake ratios were calculated by dividing lesion activity by background renal activity for both Flash 3D and QSPECT reconstructions. The difference between median (mean) hot and cold tumor uptake ratios measured 0.655 (0.73) with the QSPECT method and 0.624 (0.67) with the conventional method, resulting in increased separation between hot and cold tumors. Sub-analysis of 7 lesions near the separation point showed a higher absolute difference (0.16) between QPSECT and Flash 3D mean uptake ratios compared to the remaining lesions. Our finding of improved separation between uptake ratios of hot and cold lesions using QSPECT reconstruction lays the foundation for additional quantitative SPECT techniques such as SPECT-UV in the setting of renal 99m Tc-sestamibi and other SPECT/CT exams. With robust

  16. (99m) Tc-tricabonyl labeling of ofloxacin and its biological evaluation in Staphylococcus aureus as an infection imaging agent.

    PubMed

    Erfani, Mostafa; Doroudi, Alireza; Hadisi, Leila; Andishmand, Ali; Mirshojaei, Seyedeh Fatemeh; Shafiei, Mohammad

    2013-10-01

    Even in recent decades, one of the major causes of death and unhealthiness in the whole world is infection and inflammation. The use of radiopharmaceuticals is a powerful tool in managing the patients with infectious diseases. In this study, ofloxacin as a second-generation fluoroquinolone has been labeled with [(99m) Tc(CO)3 (H2 O)3 ](+) core to formulate a suitable infection imaging agent. Ofloxacin was radiolabeled with (99m) Tc using carbonyl core. Radioligand chemical analysis involved HPLC methods. Radioconjugate stability and lipophilicity were determined. Binding with Staphylococcus aureus and biodistribution in infected mice for labeled compound were studied. The radioligand was characterized by HPLC, and its radiochemical purity was more than 90%. In vitro stability studies have shown the complex was stable at least 6 h after labeling at room temperature. The n-octanol/water partition coefficient experiment exhibited logP = 1.52 ± 0.21 for (99m) Tc(CO)3 -ofloxacin. The complex showed specific binding to S. aureus. Biodistribution results showed that radioligand had high accumulation in the infected muscle in a mice (T/NT = 2.02 ± 0.12 at 4 h postinjection). On the basis of stability and infection site uptake ratio, suitability of this complex as a radiotracer for imaging of infections is recognized. Copyright © 2013 John Wiley & Sons, Ltd.

  17. 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

  18. The use of 99mTc-phytate for assessment the protective effect of vitamin E against hepatotoxicity induced by methotrexat in rat.

    PubMed

    Amirfakhrian, Hossein; Abedi, Seyed Mohammad; Sadeghi, Hossein; Azizi, Soheil; Hosseinimehr, Seyed Jalal

    2018-01-01

    In this study, we investigated the protective effect of vitamin E against methotrexate (MTX)-induced hepatotoxicity by quantitative liver 99mTc-phytate uptake and liver imaging and to compare its effect with histopathology in rat. Rats were divided into five groups as control, solvent, Vit E (100 mg/kg), MTX (20 mg/kg), Vit E + MTX and. Vit E was intraperitoneally administrated for 17 days before MTX injection and continued for 4 days. 99mTc-phytate was injected through the tail of rats after the drug administration. The percentage of the injected dose per gram of liver and spleen tissues (%ID/g) was calculated. Liver imaging was obtained with gamma camera. In other experiment, liver of treated rats were assessed for histopathology. 99mTc-phytate uptake per gram tissue of the livers as %ID/g in control, solvent, MTX, Vit E, Vit E + MTX and MTX groups were 8.99% ± 1.37, 8.53% ± 2.91, 8.65% ± 3.84, 3.22% ± 1.09 and 8.38% ± 2.68. Vit E administration with MTX resulted in a significant increasing in the level of %ID/g. Vit E treatment improved the shape of live in planner image. Histophatological examinations showed a protective effect of Vit E against MTX-induced hepatoxicity in rats. The results showed that Vit E significantly attenuates the MTX-induced hepatotoxicity in rats, and 99mTc-phytate uptake in liver as well as liver image to be acceptable techniques for assessment of liver and spleen damages and/or their tissues protective effects in animal model.

  19. GPER-targeted, 99mTc-labeled, nonsteroidal ligands demonstrate selective tumor imaging and in vivo estrogen binding

    PubMed Central

    Nayak, Tapan K.; Ramesh, Chinnasamy; Hathaway, Helen J.; Norenberg, Jeffrey P.; Arterburn, Jeffrey B.; Prossnitz, Eric R.

    2014-01-01

    Our understanding of estrogen (E2) receptor biology has evolved in recent years with the discovery and characterization of a 7-transmembrane-spanning G protein-coupled estrogen receptor (GPER1/GPER/GPR30) and the development of GPER-selective functional chemical probes. GPER is highly expressed in certain breast, endometrial and ovarian cancers, establishing the importance of non-invasive methods to evaluate GPER expression in vivo. Herein, we developed 99mTc-labeled GPER ligands to demonstrate the in vivo status of GPER as an estrogen receptor and for GPER visualization in whole animals. A series of 99mTc(I)-labeled non-steroidal tetrahydro-3H-cyclopenta[c]quinolone derivatives was synthesized utilizing pyridin-2-yl hydrazine and picolylamine chelates. Radioligand receptor binding studies revealed binding affinities in the 10–30 nM range. Cell signaling assays previously demonstrated that derivatives retaining a ketone functionality displayed agonist properties whereas those lacking such a hydrogen bond acceptor were antagonists. In vivo biodistribution and imaging studies performed on mice bearing human endometrial and breast cancer cell xenografts yielded significant tumor uptake (0.4–1.1 %ID/g). Blocking studies revealed specific uptake in multiple organs (adrenals, uterus, mammary tissue) as well as tumor uptake with similar levels of competition by E2 and G-1, a GPER-selective agonist. In conclusion, we synthesized and evaluated a series of first generation 99mTc-labeled GPER-specific radioligands, demonstrating GPER as an estrogen-binding receptor for the first time in vivo using competitive binding principles, and establishing the utility of such ligands as tumor imaging agents. These results warrant further investigation into the role of GPER in estrogen-mediated carcinogenesis and as a target for diagnostic/therapeutic/ image-guided drug delivery. PMID:25030373

  20. Study of Relative Quantitation of Tc-99m Annexin Localization in Pulmonary Nodules Using an Anthropomorphic Phantom

    NASA Astrophysics Data System (ADS)

    King, M.; Boening, Guido; Baker, S.; Steinmetz, N.

    2004-10-01

    In current clinical oncology practice, it often takes weeks or months of cancer therapy until a response to treatment can be identified by evaluation of tumor size in images. It is hypothesized that changes in relative localization of the apoptosis imaging agent Tc-99m Annexin before and after the administration of chemotherapy may be useful as an early indicator of the success of therapy. The objective of this study was to determine the minimum relative change in tumor localization that could be confidently determined as an increased localization. A modified version of the Data Spectrum Anthropomorphic Torso phantom, in which four spheres could be positioned in the lung region, was filled with organ concentrations of Tc-99m representative of those observed in clinical imaging of Tc-99m Annexin. Five acquisitions of an initial sphere to lung concentration, and at concentrations of 1.1, 1.2, 1.3, and 1.4 times the initial concentration, were acquired at clinically realistic count levels. The acquisitions were reconstructed by filtered backprojection, ordered subset expectation maximization (OSEM) without attenuation compensation (AC), and OSEM with AC. Permutation methodology was used to create multiple region-of-interest count ratios from the five noise realizations at each concentration and between the elevated and initial concentrations. The resulting distributions were approximated by Gaussians, which were then used to estimate the likelihood of Type 1 and Type 2 Errors. It was determined that for the cases investigated, greater than a 20% to 30% or more increase was needed to confidently determine that an increase in localization had occurred depending on sphere size and reconstruction strategy.

  1. 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.

  2. Bone scanning in lymphoma. [/sup 99m/Tc tracer technique

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

    Schechter, J.P.; Jones, S.E.; Woolfenden, J.M.

    1976-09-01

    The results of bone scanning with the newer technetium-99m complexes were correlated with clinical, laboratory, and radiographic findings in 26 patients with malignant lymphoma (10 with Hodgkin's disease and 16 with non-Hodgkin's lymphomas). Abnormalities on bone scan compatible with lymphomatous involvement of the skeleton appeared to occur more commonly in patients with diffuse lymphomas than in patients with nodular lymphomas and were generally observed in the setting of advanced disease (15 of 23 patients). Twenty-seven (73 percent) of the 37 scans obtained were abnormal. Although abnormal scans were observed with the greatest frequency in patients with bone pain (11 ofmore » 11), bone marrow involvement (11 of 12), abnormal skeletal radiographs (11 of 11), and elevated serum alkaline phosphatase levels (5 of 6), bone scanning also detected lymphomatous involvement in patients free of pain or with normal laboratory tests. Moreover, conventional radiography was entirely normal in six (35 percent) of 17 patients with abnormal scans and revealed only nonspecific osteopenia in another two patients (12 percent). Serial bone scans in nine patients reflected their response to chemotherapy. Of the 37 scans, only one was judged falsely positive and one falsely negative. Bone scanning with /sup 99m/Tc complexes is a safe, simple, and sensitive screening procedure for detecting both extensive and focal lymphomatous involvement of the skeletal system and is a useful means of following such involvement in response to treatment.« less

  3. Evaluation of normality and reproducibility parameters of scintigraphy with (99m)Tc-MAA in the diagnosis of intrapulmonary vascular dilatations.

    PubMed

    de Queirós, Andréa Simone Siqueira; Brandão, Simone Cristina Soares; Macedo, Liana Gonçalves; Ourem, Maira Souto; Mota, Vitor Gomes; Leite, Luiz Arthur Calheiros; Lopes, Edmundo Pessoa Almeida; Domingues, Ana Lúcia Coutinho

    2015-01-01

    The formation of intrapulmonary vascular dilations (IPVD) is the key event for the onset of hepatopulmonary syndrome, vascular changes secondary to portal hypertension that leads to hypoxemia. The diagnosis of IPVD can be made by contrasted transthoracic echocardiography or scintigraphy with technetium-macroaggregated albumin-((99m)Tc-MAA)-that is a sensitive and specific diagnostic method and quantifies the IPVD magnitude. However, its procedure and diagnostic indices are not yet standardized and well defined in health services. The aims of this study were to define normality values and evaluate the inter- and intra-observer reproducibility degree of diagnostic indexes of IPVD through (99m)Tc-MAA scintigraphy. Cross-sectional study was conducted at the Clinical Hospital, Federal University of Pernambuco (HC-UFPE) between July and December 2012. Fifteen patients with hepatosplenic schistosomiasis and nine patients without liver or heart disease (control group) were assessed. After clinical assessment, ultrasound and echocardiography, patients underwent (99m)Tc-MAA scintigraphy, and a relative brain uptake value exceeding 6 % or systemic uptake value exceeding 11 % was considered diagnostic of IPVD. Each assessment was performed by two independent observers. To analyze the results of the normal group, the nonparametric Bootsptrap method simulation model combined with the Monte Carlo method was used and to analyze inter- and intra-observer reproducibility indexes, the kappa and intra-class correlation coefficient were used. In normal subjects, the average brain uptake of (99m)Tc-MAA was 7.9 ± 0.01 % and systemic uptake was 12.4 ± 0.03 %, with low dispersal rates for both measures. The intra-observer agreement was 100 %, with kappa index of 1.0 (p < 0.0001), suggesting a perfect agreement. The inter-observer agreement was also 100 % (kappa = 1.0, p < 0.0001) for brain uptake; however, systemic uptake showed kappa = 0.25 (p = 0.07), which features

  4. Quantitative studies of bone in postmenopausal women using (18)F-fluoride and (99m)Tc-methylene diphosphonate.

    PubMed

    Blake, Glen M; Park-Holohan, So-Jin; Fogelman, Ignac

    2002-03-01

    Quantitative radionuclide studies of bone using the short-lived tracers (18)F-fluoride and (99m)Tc-methylene diphosphonate (MDP) are an alternative method to biochemical markers of bone turnover for investigating the dynamic state of the skeleton. In this study we evaluated their use to quantify bone turnover in women receiving antiresorptive therapy compared with that of untreated control subjects. The patients were 69 healthy postmenopausal women. Twenty-six women were receiving hormone replacement therapy (HRT) and 43 were untreated age-matched control subjects. After bolus injection of (18)F-fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid (3 MBq), and (125)I-labeled human serum albumin (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h. The clearance to bone mineral K(bone) was first evaluated using the area under the plasma concentration curve (AUC) on the assumption that the rate constant k(4) for the outflow of tracer from bone was negligibly small. AUC values of K(bone) were then compared with those found using a compartmental model method that allowed k(4) to be fitted as a free parameter. Using the AUC method the mean plus minus SD for K(bone) for the 2 tracers were: (18)F-fluoride, 61.8 plus minus 12.0 mL center dot min(-1) (HRT group) versus 67.2 plus minus 12.6 mL center dot min(-1) (control group) (P = 0.045); and (99m)Tc-MDP, 40.3 plus minus 8.2 mL center dot min(-1) (HRT group) versus 44.2 plus minus 7.6 mL center dot min(-1) (control group) (P = 0.024). Values for the 2 tracers in individual patients were moderately well correlated (r = 0.76; P < 0.001). Using the compartmental model method, k(4) for (18)F-fluoride was shown to lie in the range 0--0.0025 min(-1) with a best-fit value of 0.0018 min(-1). Values of K(bone) determined using k(4) = 0.0018 min(-1) were highly correlated with the AUC values (r = 0.989; SEE = 2.05 mL center dot min(-1)) with numeric values that were larger by

  5. In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

    PubMed

    Tofe, A J; Francis, M D

    1976-09-01

    The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

  6. Prediction of two-sample (99m)Tc-diethylene triamine pentaacetic acid plasma clearance from single-sample method.

    PubMed

    Zuo, Li; Ying-Chun; Wang, Mei; Zhang, Chun-Li; Wang, Rong-Fu; Wang, Hai-Yan

    2005-07-01

    To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1

  7. Intrapulmonary vascular dilatation evaluated by 99mTc-MAA scintigraphy and its association with portal hypertension in schistosomiasis.

    PubMed

    Queirós, Andréa Simone Siqueira de; Brandão, Simone Cristina Soares; Domingues, Ana Lúcia Coutinho; Macedo, Liana Gonçalves; Ourem, Maira Souto; Lopes, Edmundo Pessoa Almeida

    2014-06-01

    Portal hypertension is responsible for various complications in patients with schistosomiasis, among them intrapulmonary vascular dilations (IPVD). In cirrhotic patients the presence of IPVD is a sign of poor prognosis, but in patients with hepatosplenic schistosomiasis (HSS) there are no studies assessing the significance of this change. The aim of this study was to evaluate the occurrence of IPVD through 99mTc-MAA scintigraphy in patients with HSS and its relationship with clinical, laboratory, endoscopic and ultrasound parameters. Cross-sectional study evaluating 51 patients with HSS. Patients were diagnosed with IPVD when the brain uptake of 99mTc-MAA was higher than 6%. Subsequently, they were divided according to presence (G1) or absence (G2) of IPVD and variables were compared between groups. Overall, 51 patients with mean age of 56±12 years were assessed. IPVD was observed in 31 patients (60%). There was no statistically significant differences between groups when clinical, laboratory and endoscopic parameters were compared. Regarding ultrasound parameters, the splenic vein diameter was smaller in G1 (0.9 ± 0.3 cm) compared to G2 (1.2 ± 0.4 cm), p=0.029. In patients with HSS, the occurrence of IPVD by 99mTc-MAA scintigraphy was high and was associated with lower splenic vein diameter, which can be a mechanism of vascular protection against portal hypertension. However, more studies are needed to determine the clinical significance of the early diagnosis and natural evolution of IPVD in this population.

  8. Estimation of Organ Absorbed Doses in Patients from 99mTc-diphosphonate Using the Data of MIRDose Software

    PubMed Central

    Shahbazi-Gahrouei, Daryoush; Cheki, Mohsen; Moslehi, Masoud

    2012-01-01

    The purpose of this study was to compare estimation of radiation absorbed doses to patients following bone scans with technetium-99m-labeled methylene diphosphonate (MDP) with the estimates given in MIRDose software. In this study, each patient was injected 25 mCi of 99mTc-MDP. Whole-body images from thirty patients were acquired by gamma camera at 10, 60, 90, 180 minutes after 99mTc-MDP injection. To determine the amount of activity in each organ, conjugate view method was applied on images. MIRD equation was then used to estimate absorbed doses in different organs of patients. At the end, absorbed dose values obtained in this study were compared with the data of MIRDose software. The absorbed doses per unit of injected activity (mGy/MBq × 10–4) for liver, kidneys, bladder wall and spleen were 3.86 ± 1.1, 38.73 ± 4.7, 4.16 ± 1.8 and 3.91 ± 1.3, respectively. The results of this study may be useful to estimate the amount of activity that can be administered to the patient and also showed that methods used in the study for absorbed dose calculation is in good agreement with the data of MIRDose software and it is possible to use by a clinician. PMID:23724374

  9. 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

  10. Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

    PubMed

    Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

    2006-01-01

    Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

  11. Application values of 99mTc-methoxyisobutylisonitrile imaging for differentiating benign and malignant thymic masses.

    PubMed

    Lu, Chenghui; Wang, Xufu; Liu, Bin; Liu, Xinfeng; Wang, Guoming; Zhang, Qin

    2017-08-01

    The aim of the present study was to investigate the application value of 99m Tc-methoxyisobutylisonitrile (MIBI) imaging to differentiate between benign and malignant thymic masses. A total of 32 patients with space-occupying mediastinal masses were enrolled and early and delayed-phase images were collected following injection with the imaging agent. The tumor to background ratio (T/N) values at the different phases were also recorded. The sensitivity of the qualitative analysis to distinguish between benign and malignant thymic masses was 95.24%, with specificity as 90.91%. The T/N values in the early and delayed phases were not significantly different in the group with benign thymic masses, but demonstrated statistical significant differences in the groups with low- and intermediate-grade malignant thymic masses. The T/N values at the above early and delayed phase were significantly different between the benign and low-grade malignancy groups, as well as between low- and moderate-grade malignancy groups. Those between the benign and moderate-grade malignancy groups demonstrated no significant difference. 99m Tc-MIBI imaging was able to differentiate between benign and malignant thymic masses, and the simultaneous semi-quantitative analysis of the T/N values of the tumors may be able to initially determine the degree of malignancy of thymoma.

  12. 99Tc atom counting by quadrupole ICP-MS. Optimisation of the instrumental response

    NASA Astrophysics Data System (ADS)

    Más, José L.; Garcia-León, Manuel; Bolívar, Juan P.

    2002-05-01

    In this paper, an extensive work is done on the specific tune of a conventional ICP-MS for 99Tc atom counting. For this, two methods have been used and compared: the partial variable control method and the 5D Simplex method. Instrumental limits of detection of 0.2 and 0.8 ppt, respectively, were obtained. They are noticeably lower than that found with the automatic tune method of the spectrometer, 47 ppt, which shows the need of a specific tune when very low levels of 99Tc have to be determined. A study is presented on the mass interferences for 99Tc. Our experiments show that the formation of polyatomic atoms or refractory oxides as well as 98Mo hydrides seem to be irrelevant for 99Tc atom counting. The opposite occurs with the presence of isobaric interferences, i.e. 99Ru, and the effect of abundance sensitivity, or low-mass resolution, which can modify the response at m/ z=99 to a non-negligible extent.

  13. Detection of cerebral collateral circulation with Tc-99m HMPAO radionuclide angiography in cerebrovascular diseases: Delayed filling-in sign

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

    Ueno, K.

    1994-05-01

    In patients with internal carotid and major cerebral arterial obstructions, it is clinically important to know the presence of collateral circulation. However, this information is not available from Tc-99m HMPAO perfusion SPECT alone. To investigate the usefulness of Tc-99m HMPAO radionuclide angiography (RNA) in the diagnosis of collaterals, we retrospectively studied 39 patients (pts) cerebrovascular diseases (CVD) with HMPAO RNA and SPECT. Contrast angiography was done on all pts. Of these, 11 internal carotid artery (ICA), 1 anterior cerebral artery (ACA), and 3 middle cerebral artery (MCA) obstructions were found angiographically. Non- or decreased visualization of ICA was found inmore » 11 of 11 pts of ICA obstruction. In 1 pt of ICA obstruction, the collaterals were directly visualized with RNA. Early perfusion deficient area with delayed filling-in with Tc-HMPAO was found in 7 of 11 pts of ICA, 1 of 1 pt of ACA, and 2 of 3 pts of MCA obstructions. In all pts with the delayed filling-in sign on RNA, collateral circulations were confirmed angiographically. We conclude that the delayed filling-in of Tc-HMPAO is a useful sign of collateral circulation in the CVD pts.« less

  14. Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules

    PubMed Central

    Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-01-01

    [99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained. PMID:29212258

  15. Comparative assessment of a 99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging.

    PubMed

    Torabizadeh, Seyedeh Atekeh; Abedi, Seyed Mohammad; Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

    2017-05-01

    Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with 99m Tc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptide was labeled with 99m Tc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27%±0.46% and 1.55%±0.20% for tricine and 2.34±1.1% and 1.09%±0.18% for EDDA/tricine at 1 and 4h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new 99m Tc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of 99m Tc-labeled H1299.2 for tumor imaging in animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A (99m) Tc-tricine-HYNIC-labeled peptide targeting the neurotensin receptor for single-photon imaging in malignant tumors.

    PubMed

    Erfani, Mostafa; Zarrabi Ahrabi, Nakisa; Shafiei, Mohammad; Shirmardi, Seyed Pezhman

    2014-03-01

    In this study, a new neurotensin (NT) analog was labeled with (99m) Tc via HYNIC chelator and tricine as coligand and investigated further. An NT (7-13) analog was prepared, and labeling with (99m) Tc was performed. The internalization rate and biodistribution of radiopeptide were studied in HT-29 cells and nude mice bearing tumor, respectively. Radiolabeling with (99m) Tc was performed at high specific activities (54 MBq/nmol) with an acceptable labeling yield (>95%). In vitro cell line studies showed a specific internalization uptake up to 13.23 ± 0.45% during 4 h which was blocked in the presence of excess cold peptide to 0.83 ± 0.15%. In biodistribution studies, uptake was observed in NT receptor-positive organs so that after 1 h the uptakes in mouse intestine and tumor were 1.23 ± 0.16% ID/g and 1.12 ± 0.11% ID/g, respectively. In animals co-injected with excess cold peptide, reduction uptake in tumor and intestines were 73% (1.10% vs. 0.29% ID/g at 4 h) and 61% (1.22% vs. 0.47% ID/g at 4 h) respectively. Predominant renal excretion pathway with a highest accumulation of activity in bladder was observed for this radiopeptide. This radiolabeled peptide could be a candidate for detection of NT positive tumors. Copyright © 2014 John Wiley & Sons, Ltd.

  17. 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

  18. 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

  19. Measuring functioning hepatocytes using Tc-99m galactosylneoglycoalbumin (Tc-NGA)

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

    Stadalnik, R.C.; Vera, D.R.; Quadro, R.E.

    1984-01-01

    Tc-NGA is a synthetic ligand which binds only to hepatic binding protein (HBP), a receptor found only in the liver. It exhibits the properties of high tissue specificity, affinity-dependent uptake, and dose-dependent uptake. Tc-NGA provides an opportunity to study the functioning hepatocyte. The authors evaluated the usefulness of this technique in patients with hepatitis and hepatoma. After intravenous administration of 5 mCi Tc-NGA, dynamic images were acquired for 30 minutes followed by static views. Estimates of HBP concentrations were obtained by kinetic analysis of blood and liver time-activity curves. Kinetic estimates (reduced chi-squares < 3.0) of HBP correlated well withmore » the clinical course and histology. For example, a patient with hepatoma whose calculated receptor population (functioning hepatocytes) was 3.0 +- 0.9 x 10/sup -7/ mole, which is the normal range, is doing well undergoing chemotherapy. Liver biopsy demonstrated normal liver tissue except for the hepatoma. Another patient with hepatoma who had a severely depressed receptor population, 1.2 +- 0.2 x 10/sup -8/ mole, expired one week after the study. Liver biopsy demonstrated practically no normal tissue. Thus, by means of a complementary, receptor radiopharmaceutical and mathematical model, one should be able to quantitatively follow hepatocyte function and predict response to a therapeutic regimen.« less

  20. Technetium-99m: basic nuclear physics and chemical properties.

    PubMed

    Castronovo, F P

    1975-05-01

    The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.

  1. 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

  2. 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.

  3. 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

  4. Method and kit for the selective labeling of red blood cells in whole blood with TC-99M

    DOEpatents

    Srivastava, Suresh C.; Babich, John W.; Straub, Rita; Richards, Powell

    1988-01-01

    Disclosed herein are a method and kit for the preparation of .sup.99m Tc labeled red blood cells using whole blood in a closed sterile system containing stannous tin in a form such that it will enter the red blood cells and be available therein for the reduction of technetium.

  5. 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

  6. Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

    PubMed

    Bailey, J J; Dewaraja, Y; Hubers, D; Srinivasa, R N; Frey, K A

    2017-10-01

    To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

  7. 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 99mTc-(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 99mTc 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. 99mTc-(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 99mTc-(tricine)-HYNIC-(Ser) 3 -J18 is better than previously reported radiolabeled peptide as 99mTc-(EDDA/tricine)-HYNIC-(Ser) 3 -J18 for NSCLC targeting and imaging. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. 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.

  9. Absolute activity quantitation from projections using an analytical approach: comparison with iterative methods in Tc-99m and I-123 brain SPECT

    NASA Astrophysics Data System (ADS)

    Fakhri, G. El; Kijewski, M. F.; Moore, S. C.

    2001-06-01

    Estimates of SPECT activity within certain deep brain structures could be useful for clinical tasks such as early prediction of Alzheimer's disease with Tc-99m or Parkinson's disease with I-123; however, such estimates are biased by poor spatial resolution and inaccurate scatter and attenuation corrections. We compared an analytical approach (AA) of more accurate quantitation to a slower iterative approach (IA). Monte Carlo simulated projections of 12 normal and 12 pathologic Tc-99m perfusion studies, as well as 12, normal and 12 pathologic I-123 neurotransmission studies, were generated using a digital brain phantom and corrected for scatter by a multispectral fitting procedure. The AA included attenuation correction by a modified Metz-Fan algorithm and activity estimation by a technique that incorporated Metz filtering to compensate for variable collimator response (VCR), IA-modeled attenuation, and VCR in the projector/backprojector of an ordered subsets-expectation maximization (OSEM) algorithm. Bias and standard deviation over the 12 normal and 12 pathologic patients were calculated with respect to the reference values in the corpus callosum, caudate nucleus, and putamen. The IA and AA yielded similar quantitation results in both Tc-99m and I-123 studies in all brain structures considered in both normal and pathologic patients. The bias with respect to the reference activity distributions was less than 7% for Tc-99m studies, but greater than 30% for I-123 studies, due to partial volume effect in the striata. Our results were validated using I-123 physical acquisitions of an anthropomorphic brain phantom. The IA yielded quantitation accuracy comparable to that obtained with IA, while requiring much less processing time. However, in most conditions, IA yielded lower noise for the same bias than did AA.

  10. Method and kit for the selective labeling of red blood cells in whole blood with Tc-99m

    DOEpatents

    Srivastava, S.C.; Babich, J.W.; Straub, R.; Richards, P.

    1988-07-05

    Disclosed herein are a method and kit for the preparation of [sup 99m]Tc labeled red blood cells using whole blood in a closed sterile system containing stannous tin in a form such that it will enter the red blood cells and be available for the reduction of technetium. No Drawings

  11. 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

  12. Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C.

    PubMed

    Salihoglu, Yavuz Sami; Elri, Tarik; Gulle, Kanat; Can, Murat; Aras, Mustafa; Ozacmak, Hale Sayan; Cabuk, Mehmet

    2016-10-01

    The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity. Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5 mg/kg intraperitoneally); (3) Agmatine (AGM; 10 mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP + AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation. In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone. Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.

  13. The uptake by the canine tibia of the bone-scanning agent 99mTc-MDP before and after an osteotomy.

    PubMed

    Hughes, S; Khan, R; Davies, R; Lavender, P

    1978-11-01

    The residue and extraction of technetium-labelled methylene diphosphonate (99mTc-MDP), a substance used in bone scanning, was examined in the canine tibia and found to be low. Examination of washout curves suggested that there were four compartments in cortical bone, a vascular, a perivascular, a bone fluid and a bone compartment. After an osteotomy in the canine tibia the residue of 99mTc-MDP increased. This was believed to be due to an increase in the blood supply to the bone and to an associated increase in new bone available for exchange. Bone scanning in a fracture is therefore a reflection of the vascular status of the bone being examined and of the uptake by bone. This is dependent on there being an adequate blood supply to the bone and an increased number of mineral-binding sites.

  14. Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a preliminary communication.

    PubMed

    Płachcińska, Anna; Mikołajczak, Renata; Maecke, Helmut R; Młodkowska, Ewa; Kunert-Radek, Jolanta; Michalski, Andrzej; Rzeszutek, Katarzyna; Kozak, Józef; Kuśmierek, Jacek

    2003-10-01

    This study assessed the clinical usefulness of a new technetium-99m labelled somatostatin analogue from the standpoint of oncological diagnostics. The study group comprised 40 patients in whom malignant neoplasms (32 primary and 8 metastatic) had been diagnosed. Among the primary tumours there were 21 cases of lung cancer (2 small cell and 19 non-small cell), seven pituitary adenomas (five hormonally active and two inactive), one liposarcoma, two carcinoids and one breast carcinoma. The metastatic tumours consisted of three malignant melanomas, one phaeochromocytoma, one prostatic cancer, one leiomyosarcoma, one pancreatic carcinoma ectopically secreting ACTH and one carcinoid of the thymus. The radiopharmaceutical 99mTc-EDDA/HYNIC-Tyr3-octreotide was administered i.v. at an activity of 740-925 MBq. The imaging comprised a whole-body scan and a single-photon emission tomography acquisition. Positive scintigrams were obtained in all cases of small cell and non-small cell lung cancer, four out of five hormonally active pituitary adenomas, one out of two cases of carcinoid, the liposarcoma and the breast cancer. Neoplastic metastases were visualised in two out of three patients with melanoma and in patients with phaeochromocytoma, ACTH-secreting pancreatic carcinoma and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, in the leiomyosarcoma and in the case of metastasis from prostatic carcinoma. The results of this pilot study indicate that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for imaging of a wide range of primary and metastatic tumours. Special attention should be paid to the successful imaging of all cases of non-small cell lung cancer.

  15. Oral (99m)Tc-DTPA simultaneous determination of duodenobiliary reflux and intestinal permeability in patients after choledocholithotomy plus T-tube drainage.

    PubMed

    Sun, Shao-Long; Wu, Shuo-Dong; Zhang, Xiao-Bo

    2005-11-01

    The high choledocholithiasis recurrence rate after choledocholithotomy plus T-tube drainage is related to biliary bacterial infection. These bacteria are from the intestine, either via the major duodenal papilla, or the penetrating intestinal mucosa. It is therefore possible that duodenobiliary reflux and increased intestinal permeability exist in patients who have undergone choledocholithotomy. This study was undertaken to find the evidence of duodenobiliary reflux and to assess intestinal permeability in these patients. Twenty-one patients who underwent choledocholithotomy plus T-tube drainage 2 months ago, and 11 healthy volunteers (controls) took orally 185MBq of (99m)Tc-DTPA. The patients' bile was collected in the next 2 hours via a T-tube and the (99m)Tc-DTPA radioactivity in the bile was counted. Intestinal permeability was evaluated by measuring the 24-hour urinary excretion rate of ingested (99m)Tc-DTPA in both patients and controls. In 6 of the 21 patients, radioactivity in the bile was detected. The intestinal permeability was significantly higher in patients (11.45%+/-6.16%) than that in controls (3.61%+/-1.63%, t=3.28, P<0.05). Duodenobiliary reflux exists in patients who have undergone choledocholithotomy plus T-tube drainage. The intestinal permeability is higher in these patients than in healthy subjects. Duodenobiliary reflux and increased intestinal permeability may be factors of cholelithiasis recurrence.

  16. The significance of 99mTc-MAA SPECT/CT liver perfusion imaging in treatment planning for 90Y-microsphere selective internal radiation treatment.

    PubMed

    Ahmadzadehfar, Hojjat; Sabet, Amir; Biermann, Kim; Muckle, Marianne; Brockmann, Holger; Kuhl, Christiane; Wilhelm, Kai; Biersack, Hans-Jürgen; Ezziddin, Samer

    2010-08-01

    Selective internal radiation therapy (SIRT), a catheter-based liver-directed modality for treating primary and metastatic liver cancer, requires appropriate planning to maximize its therapeutic response and minimize its side effects. (99m)Tc-macroaggregated albumin (MAA) scanning should precede the therapy to detect any extrahepatic shunting to the lung or gastrointestinal tract. Our aim was to compare the ability of SPECT/CT with that of planar imaging and SPECT in the detection and localization of extrahepatic (99m)Tc-MAA accumulation and to evaluate the impact of SPECT/CT on SIRT treatment planning and its added value to angiography in this setting. Ninety diagnostic hepatic angiograms with (99m)Tc-MAA were obtained for 76 patients with different types of cancer. All images were reviewed retrospectively for extrahepatic MAA deposition in the following order: planar, non-attenuation-corrected SPECT, and SPECT/CT. Review of angiograms and follow-up of patients with abdominal shunting served as reference standards. Extrahepatic accumulation was detected by planar imaging, SPECT, and SPECT/CT in 12%, 17%, and 42% of examinations, respectively. The sensitivity for detecting extrahepatic shunting with planar imaging, SPECT, and SPECT/CT was 32%, 41%, and 100%, respectively; specificity was 98%, 98%, and 93%, respectively. The respective positive predictive values were 92%, 93%, and 89%, and the respective negative predictive values were 71%, 73%, and 100%. The therapy plan was changed according to the results of planar imaging, SPECT, and SPECT/CT in 7.8%, 8.9%, and 29% of patients, respectively. In pre-SIRT planning, (99m)Tc-MAA SPECT/CT is valuable for identifying extrahepatic visceral sites at risk for postradioembolization complications.

  17. Liver Function in Areas of Hepatic Venous Congestion After Hepatectomy for Liver Cancer: 99mTc-GSA SPECT/CT Fused Imaging Study.

    PubMed

    Yoshida, Morikatsu; Beppu, Toru; Shiraishi, Shinya; Tsuda, Noriko; Sakamoto, Fumi; Kuramoto, Kunitaka; Okabe, Hirohisa; Nitta, Hidetoshi; Imai, Katsunori; Tomiguchi, Seiji; Baba, Hideo; Yamashita, Yasuyuki

    2018-05-01

    Background/Aim: The sacrifice of a major hepatic vein can cause hepatic venous congestion (HVC). We evaluated the effects of HVC on regional liver function using the liver uptake value (LUV), that was calculated from 99m Tc-labeled-galactosyl-human-serum-albumin ( 99m Tc-GSA) single-photon emission computed tomography (SPECT) /contrast-enhanced computed tomography (CE-CT) fused images. Patients and Methods: Sixty-two patients underwent 99m Tc-GSA SPECT/CE-CT prior to hepatectomy for liver cancer and at 7 days after surgery were divided into groups with (n=8) and without HVC (n=54). In the HVC group, CT volume (CTv) and LUV were separately calculated in both congested and non-congested areas. Results: The remnant LUV/CTv of the HVC group was significantly smaller than that of the non-HVC group (p<0.01). The mean functional ratio was 0.47±0.05, and all ratios were ≥0.39. Conclusion: After hepatectomy with sacrifice of major hepatic vein, liver function per unit volume in the congested areas was approximately 40% of that in the non-congested areas. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Liver function assessment using 99mTc-GSA single-photon emission computed tomography (SPECT)/CT fusion imaging in hilar bile duct cancer: A retrospective study.

    PubMed

    Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Hata, Yasuhiro; Noda, Yoshihiro; Kouno, Michihiko; Miyagawa, Kazuyuki; Tokorodani, Ryotaro; Saisaka, Yuichi; Tokumaru, Teppei; Nakamura, Toshio; Morita, Sojiro

    2016-07-01

    The objective of this study was to determine the utility of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging for posthepatectomy remnant liver function assessment in hilar bile duct cancer patients. Thirty hilar bile duct cancer patients who underwent major hepatectomy with extrahepatic bile duct resection were retrospectively analyzed. Indocyanine green plasma clearance rate (KICG) value and estimated KICG by (99m)Tc-GSA scintigraphy (KGSA) and volumetric and functional rates of future remnant liver by (99m)Tc-GSA SPECT/CT fusion imaging were used to evaluate preoperative whole liver function and posthepatectomy remnant liver function, respectively. Remnant (rem) KICG (= KICG × volumetric rate) and remKGSA (= KGSA × functional rate) were used to predict future remnant liver function; major hepatectomy was considered unsafe for values <0.05. The correlation of remKICG and remKGSA with posthepatectomy mortality and morbidity was determined. Although remKICG and remKGSA were not significantly different (median value: 0.071 vs 0.075), functional rates of future remnant liver were significantly higher than volumetric rates (median: 0.54 vs 0.46; P < .001). Hepatectomy was considered unsafe in 17% and 0% of patients using remKICG and remKGSA, respectively. Postoperative liver failure and mortality did not occur in the patients for whom hepatectomy was considered unsafe based on remKICG. remKGSA showed a stronger correlation with postoperative prothrombin time activity than remKICG. (99m)Tc-GSA SPECT/CT fusion imaging enables accurate assessment of future remnant liver function and suitability for hepatectomy in hilar bile duct cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

    PubMed Central

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-01-01

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

  20. A rare case of suprahepatic gall bladder with phocomelia and pancytopenia: detected by tc-99m mebrofenin scintigraphy.

    PubMed

    Rather, Tanveeer Ah; Khan, Shoukat H; Singh, Manjeet; Choh, Naseer A

    2013-01-01

    The possibility of an ectopic gallbladder should always be considered whenever there is a failure to localize it in its normal anatomical position on routine imaging. Although a very rare entity, the anomalous position of gallbladder can result in misinterpretation of imaging findings and create clinical confusion. Awareness of such an anomaly facilitates proper diagnosis and subsequent management. The authors report a very rare case of suprahepatic gallbladder associated with phocomelia, pancytopenia, and splenomegaly in a young 25-year-old female. The suprahepatic gallbladder was initially visualized on Technetium-99m (Tc-99m) Mebrofenin radionuclide hepatobiliary scintigraphy. Subsequent magnetic resonance cholecystopancreatography (MRCP) was also done to confirm the diagnosis.