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.

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.

A secular technetium-molybdenum generator

NASA Astrophysics Data System (ADS)

Araujo, Wagner L.; Campos, Tarcisio P. R.

2015-05-01

A compact secular molybdenium generator is subject of this paper. This generator represents a nuclear system that comprises a hydrogen-isotopes fusor, moderator, reflector and shield. Deuterium fusion reactions in a tritiated or deuterated target provide the neutron source. A moderation fluid slowdown the neutron energy which increases 98Mo(n,γ)99Mo capture reaction rates. Neutron reflection minimizes the neutron escape and the radiation shield encloses the device. The neutron yield calculation along with electromagnetic and nuclear simulations were addressed. Results revealed the accelerator equipotential surfaces ranging from -30 to 150 kV, the ion trajectories and the energy beam profile define a deuteron current of 1 A with energy of 180 keV at the target, the spatial distribution of the neutron flux, and the 99Mo and 99mTc activities in function of transmuter operation time. The kinetics of the 99mTc correlated to its precursor activity demonstrates a secular equilibrium providing 2 Ci in a operational time of 150 h. As conclusion, the investigated nuclear and electromagnetic features have demonstrated that such generator shall have a notable potential for feeding the 99mTc clinical application.

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.

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

NASA Astrophysics Data System (ADS)

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

2015-05-01

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

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.

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.

A Generator-Produced Gallium-68 Radiopharmaceutical for PET Imaging of Myocardial Perfusion

PubMed Central

Sharma, Vijay; Sivapackiam, Jothilingam; Harpstrite, Scott E.; Prior, Julie L.; Gu, Hannah; Rath, Nigam P.; Piwnica-Worms, David

2014-01-01

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI. PMID:25353349

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

PubMed

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

2013-11-01

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

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates.

PubMed

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

2016-01-21

In response to the recognized fragility of reactor-produced (99)Mo supply, direct production of (99m)Tc via (100)Mo(p,2n)(99m)Tc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with (99m)Tc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical (99m)Tc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

Molybdenum target specifications for cyclotron production of 99mTc based on patient dose estimates

NASA Astrophysics Data System (ADS)

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

2016-01-01

In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produced. They will be incorporated into the labeled radiopharmaceuticals and result in increased patient dose. The isotopic composition of the target and beam energy are main factors that determine production of impurities, thus also dose increases. Therefore, they both must be considered when selecting targets for clinical 99mTc production. Although for any given Mo target, the patient dose can be predicted based on complicated calculations of production yields for each Tc radioisotope, it would be very difficult to reverse these calculations to specify target composition based on dosimetry considerations. In this article, a relationship between patient dosimetry and Mo target composition is studied. A simple and easy algorithm for dose estimation, based solely on the knowledge of target composition and beam energy, is described. Using this algorithm, the patient dose increase due to every Mo isotope that could be present in the target is estimated. Most importantly, a technique to determine Mo target composition thresholds that would meet any given dosimetry requirement is proposed.

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.

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

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.

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.

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

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

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

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

PubMed

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

2015-01-01

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

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

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

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

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

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

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

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

PubMed

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

1994-04-01

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

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.

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

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.

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

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

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.

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.

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 ...

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.

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.

Effect of Thuya occidentalis on the labeling of red blood cells and plasma proteins with technetium-99m.

PubMed Central

Oliveira, J. F.; Braga, A. C.; Avila, A. S.; Fonseca, L. M.; Gutfilen, B.; Bernardo-Filho, M.

1996-01-01

Thuya occidentalis is used in popular medicine in the treatment of condyloma and has antibacterial action. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. This labeling depends on a reducing agent, usually stannous ion. Any drug which alters the labeling of the tracer could be expected to modify the disposition of the radiopharmaceutical. We have evaluated the influence of T. occidentalis extract on the labeling of RBC and plasma proteins with 99mTc. Blood was withdrawn and incubated with T. occidentalis (0.25; 2.5; 20.5; and 34.1 percent v/v). Stannous chloride (1.2 micrograms/ml) was added and then 99mTc was added. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) separated. The analysis of the results shows that there is a decrease in radioactivity (from 97.64 to 75.89 percent) in BC with 34.1 percent of the drug. In the labeling process of RBC with 99mTc, the stannous and pertechnetate ions pass through the membrane, so we suggest that the T. occidentalis effect can be explained (i) by an inhibition of the transport of these ions, (ii) by damage in membrane, (iii) by competition with the cited ions for the same binding sites, or (iv) by possible generation of reactive oxygen species that could oxidize the stannous ion. PMID:9436292

Effect of Thuya occidentalis on the labeling of red blood cells and plasma proteins with technetium-99m.

PubMed

Oliveira, J F; Braga, A C; Avila, A S; Fonseca, L M; Gutfilen, B; Bernardo-Filho, M

1996-01-01

Thuya occidentalis is used in popular medicine in the treatment of condyloma and has antibacterial action. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. This labeling depends on a reducing agent, usually stannous ion. Any drug which alters the labeling of the tracer could be expected to modify the disposition of the radiopharmaceutical. We have evaluated the influence of T. occidentalis extract on the labeling of RBC and plasma proteins with 99mTc. Blood was withdrawn and incubated with T. occidentalis (0.25; 2.5; 20.5; and 34.1 percent v/v). Stannous chloride (1.2 micrograms/ml) was added and then 99mTc was added. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) separated. The analysis of the results shows that there is a decrease in radioactivity (from 97.64 to 75.89 percent) in BC with 34.1 percent of the drug. In the labeling process of RBC with 99mTc, the stannous and pertechnetate ions pass through the membrane, so we suggest that the T. occidentalis effect can be explained (i) by an inhibition of the transport of these ions, (ii) by damage in membrane, (iii) by competition with the cited ions for the same binding sites, or (iv) by possible generation of reactive oxygen species that could oxidize the stannous ion.

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.

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.

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.

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

PubMed

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

2006-06-01

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

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

PubMed Central

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

2006-01-01

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

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

PubMed

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

2005-09-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2010-01-01

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

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.

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.

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

Dale, Gregory E.

There is currently a serious shortage of 99Mo, from which to generate the medically significant isotope 99mTc. Most of the world's supply comes from the fission of highly enriched uranium targets--this is a proliferation concern. This document focuses on the technology involved in two alternative methods: electron accelerator production of 99Mo from the 100Mo(γ,n) 99Mo reaction and production of 99Mo as a fission product in a subcritical, DT accelerator-driven low enriched uranium salt solution.

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 have the possible application to simplify the synthesis of the pharmaceutical. The versatility of the oxidation states of these metals leads to numerous possibilities in developing new radiopharmaceuticals. The coordination chemistry and reaction mechanisms must be efficiently characterized to ensure the reproducibility of the radiopharmaceutical. The current study focuses on technetium and rhenium complexes with peptides. These complexes have become increasing interesting for their use in diagnostic and therapeutic radiopharmaceuticals. The characterization of the complexation of Tc(V), and Rh(V) with the pentapeptide KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine) will be discussed. Complexes will be characterized by High Performance Liquid Chromatography (HPLC), UV-Visible Spectroscopy, Proton NMR, Circular Dichroism (CD), and Electrospray Ionization Mass Spectroscopy, to compare them to current radiopharmaceuticals. Information on the underlying reactions and coordination will be discussed.

Semi-Quantitative Analysis of Post-Transarterial Radioembolization (90)Y Microsphere Positron Emission Tomography Combined with Computed Tomography (PET/CT) Images in Advanced Liver Malignancy: Comparison With (99m)Tc Macroaggregated Albumin (MAA) Single Photon Emission Computed Tomography (SPECT).

PubMed

Rhee, Seunghong; Kim, Sungeun; Cho, Jaehyuk; Park, Jukyung; Eo, Jae Seon; Park, Soyeon; Lee, Eunsub; Kim, Yun Hwan; Choe, Jae-Gol

2016-03-01

The purpose of this study is to evaluate the correlation between pretreatment planning technetium-99m ((99m)Tc) macroaggregated albumin (MAA) SPECT images and posttreatment transarterial radioembolization (TARE) yttirum-90 ((90)Y) PET/CT images by comparing the ratios of tumor-to-normal liver counts. Fifty-two patients with advanced hepatic malignancy who underwent (90)Y microsphere radioembolization from January 2010 to December 2012 were retrospectively reviewed. Patients had undergone (99m)Tc MAA intraarterial injection SPECT for a pretreatment evaluation of microsphere distribution and therapy planning. After the administration of (90)Y microspheres, the patients underwent posttreatment (90)Y PET/CT within 24 h. For semiquantitative analysis, the tumor-to-normal uptake ratios in (90)Y PET/CT (TNR-yp) and (99m)Tc MAA SPECT (TNR-ms) as well as the tumor volumes measured in angiographic CT were obtained and analyzed. The relationship of TNR-yp and TNR-ms was evaluated by Spearman's rank correlation and Wilcoxon's matched pairs test. In a total of 79 lesions of 52 patients, the distribution of microspheres was well demonstrated in both the SPECT and PET/CT images. A good correlation was observed of between TNR-ms and TNR-yp (rho value = 0.648, p < 0.001). The TNR-yp (median 2.78, interquartile range 2.43) tend to show significantly higher values than TNR-ms (median 2.49, interquartile range of 1.55) (p = 0.012). The TNR-yp showed weak correlation with tumor volume (rho = 0.230, p = 0.041). The (99m)Tc MAA SPECT showed a good correlation with (90)Y PET/CT in TNR values, suggesting that (99m)Tc MAA can be used as an adequate pretreatment evaluation method. However, the (99m)Tc MAA SPECT image consistently shows lower TNR values compared to (90)Y PET/CT, which means the possibility of underestimation of tumorous uptake in the partition dosimetry model using (99m)Tc MAA SPECT. Considering that (99m)Tc MAA is the only clinically available surrogate marker for distribution of microsphere, we recommend measurement of tumorous uptake using (90)Y PET/CT should be included routinely in the posttherapeutic evaluation.

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.

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.

A 3D Computational fluid dynamics model validation for candidate molybdenum-99 target geometry

NASA Astrophysics Data System (ADS)

Zheng, Lin; Dale, Greg; Vorobieff, Peter

2014-11-01

Molybdenum-99 (99Mo) is the parent product of technetium-99m (99mTc), a radioisotope used in approximately 50,000 medical diagnostic tests per day in the U.S. The primary uses of this product include detection of heart disease, cancer, study of organ structure and function, and other applications. The US Department of Energy seeks new methods for generating 99Mo without the use of highly enriched uranium, to eliminate proliferation issues and provide a domestic supply of 99mTc for medical imaging. For this project, electron accelerating technology is used by sending an electron beam through a series of 100Mo targets. During this process a large amount of heat is created, which directly affects the operating temperature dictated by the tensile stress limit of the wall material. To maintain the required temperature range, helium gas is used as a cooling agent that flows through narrow channels between the target disks. In our numerical study, we investigate the cooling performance on a series of new geometry designs of the cooling channel. This research is supported by Los Alamos National Laboratory.

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

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.

Graphical user interface for yield and dose estimations for cyclotron-produced technetium

NASA Astrophysics Data System (ADS)

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

2014-07-01

The cyclotron-based 100Mo(p,2n)99mTc reaction has been proposed as an alternative method for solving the shortage of 99mTc. With this production method, however, even if highly enriched molybdenum is used, various radioactive and stable isotopes will be produced simultaneously with 99mTc. In order to optimize reaction parameters and estimate potential patient doses from radiotracers labeled with cyclotron produced 99mTc, the yields for all reaction products must be estimated. Such calculations, however, are extremely complex and time consuming. Therefore, the objective of this study was to design a graphical user interface (GUI) that would automate these calculations, facilitate analysis of the experimental data, and predict dosimetry. The resulting GUI, named Cyclotron production Yields and Dosimetry (CYD), is based on Matlab®. It has three parts providing (a) reaction yield calculations, (b) predictions of gamma emissions and (c) dosimetry estimations. The paper presents the outline of the GUI, lists the parameters that must be provided by the user, discusses the details of calculations and provides examples of the results. Our initial experience shows that the proposed GUI allows the user to very efficiently calculate the yields of reaction products and analyze gamma spectroscopy data. However, it is expected that the main advantage of this GUI will be at the later clinical stage when entering reaction parameters will allow the user to predict production yields and estimate radiation doses to patients for each particular cyclotron run.

Graphical user interface for yield and dose estimations for cyclotron-produced technetium.

PubMed

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

2014-07-07

The cyclotron-based (100)Mo(p,2n)(99m)Tc reaction has been proposed as an alternative method for solving the shortage of (99m)Tc. With this production method, however, even if highly enriched molybdenum is used, various radioactive and stable isotopes will be produced simultaneously with (99m)Tc. In order to optimize reaction parameters and estimate potential patient doses from radiotracers labeled with cyclotron produced (99m)Tc, the yields for all reaction products must be estimated. Such calculations, however, are extremely complex and time consuming. Therefore, the objective of this study was to design a graphical user interface (GUI) that would automate these calculations, facilitate analysis of the experimental data, and predict dosimetry. The resulting GUI, named Cyclotron production Yields and Dosimetry (CYD), is based on Matlab®. It has three parts providing (a) reaction yield calculations, (b) predictions of gamma emissions and (c) dosimetry estimations. The paper presents the outline of the GUI, lists the parameters that must be provided by the user, discusses the details of calculations and provides examples of the results. Our initial experience shows that the proposed GUI allows the user to very efficiently calculate the yields of reaction products and analyze gamma spectroscopy data. However, it is expected that the main advantage of this GUI will be at the later clinical stage when entering reaction parameters will allow the user to predict production yields and estimate radiation doses to patients for each particular cyclotron run.

Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

PubMed Central

Li, Yanli; Hu, Yan; Xiao, Jie; Liu, Guobing; Li, Xiao; Zhao, Yanzhao; Tan, Hui; Shi, Hongcheng; Cheng, Dengfeng

2016-01-01

SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy. PMID:27649935

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.

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

Effects of CT-based attenuation correction of rat microSPECT images on relative myocardial perfusion and quantitative tracer uptake

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

Strydhorst, Jared H., E-mail: jared.strydhorst@gmail.com; Ruddy, Terrence D.; Wells, R. Glenn

2015-04-15

Purpose: Our goal in this work was to investigate the impact of CT-based attenuation correction on measurements of rat myocardial perfusion with {sup 99m}Tc and {sup 201}Tl single photon emission computed tomography (SPECT). Methods: Eight male Sprague-Dawley rats were injected with {sup 99m}Tc-tetrofosmin and scanned in a small animal pinhole SPECT/CT scanner. Scans were repeated weekly over a period of 5 weeks. Eight additional rats were injected with {sup 201}Tl and also scanned following a similar protocol. The images were reconstructed with and without attenuation correction, and the relative perfusion was analyzed with the commercial cardiac analysis software. The absolutemore » uptake of {sup 99m}Tc in the heart was also quantified with and without attenuation correction. Results: For {sup 99m}Tc imaging, relative segmental perfusion changed by up to +2.1%/−1.8% as a result of attenuation correction. Relative changes of +3.6%/−1.0% were observed for the {sup 201}Tl images. Interscan and inter-rat reproducibilities of relative segmental perfusion were 2.7% and 3.9%, respectively, for the uncorrected {sup 99m}Tc scans, and 3.6% and 4.3%, respectively, for the {sup 201}Tl scans, and were not significantly affected by attenuation correction for either tracer. Attenuation correction also significantly increased the measured absolute uptake of tetrofosmin and significantly altered the relationship between the rat weight and tracer uptake. Conclusions: Our results show that attenuation correction has a small but statistically significant impact on the relative perfusion measurements in some segments of the heart and does not adversely affect reproducibility. Attenuation correction had a small but statistically significant impact on measured absolute tracer uptake.« less

.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.

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.

Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation.

PubMed

Meads, C; Sutton, A; Małysiak, S; Kowalska, M; Zapalska, A; Rogozinska, E; Baldwin, P; Rosenthal, A; Ganesan, R; Borowiack, E; Barton, P; Roberts, T; Sundar, S; Khan, K

2013-12-01

Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. The National Institute for Health Research Health Technology Assessment programme.

Diagnostic and Therapeutic Radiopharmaceutical Agents for Selective Discrimination of Prostate Cancer

DTIC Science & Technology

2008-10-01

complexing a M(CO)3 (Re,99mTc) organometallic species to target prostate cancer for imaging and therapy . The project has been successful in developing and...couple flutamide derivatives with new ligand systems. New methods were investigated on a fundamental level prior to functionalization with the ...based on the current results of the first generation compounds. The 2+1 approach was initially investigated for coupling the Tc(CO)3 to a multi

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

Chemerisov, S.; Bailey, J.; Heltemes, T.

A series of four one-day irradiations was conducted with 100Mo-enriched disk targets. After irradiation, the enriched disks were removed from the target and dissolved. The resulting solution was processed using a NorthStar RadioGenix™ 99mTc generator either at Argonne National Laboratory or at the NorthStar Medical Radioisotopes facility. Runs on the RadioGenix system produced inconsistent analytical results for 99mTc in the Tc/Mo solution. These inconsistencies were attributed to the impurities in the solution or improper column packing. During the irradiations, the performance of the optic transitional radiation (OTR) and infrared cameras was tested in high radiation field. The OTR cameras survivedmore » all irradiations, while the IR cameras failed every time. The addition of X-ray and neutron shielding improved camera survivability and decreased the number of upsets.« less

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.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

PubMed Central

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Methods: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID:27408857

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours.

PubMed

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

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.

WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

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

Taborda, A; Benabdallah, N; Desbree, A

2015-06-15

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres ofmore » unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.« less

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

PubMed

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

2007-10-01

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

PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

PubMed

Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

2010-11-01

A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ might confer to this novel compound an important role for the development of new (99m)Tc and (188)Re-nitrido radiopharmaceuticals. Copyright © 2010 Elsevier Inc. All rights reserved.

Theoretical modeling of yields for proton-induced reactions on natural and enriched molybdenum targets.

PubMed

Celler, A; Hou, X; Bénard, F; Ruth, T

2011-09-07

Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated, as these may affect the diagnostic outcome and radiation dosimetry in human studies. Reaction conditions (beam and target characteristics, and irradiation and cooling times) need to be optimized in order to maximize the amount of (99m)Tc and minimize impurities. Although ultimately careful experimental verification of these conditions must be performed, theoretical calculations can provide the initial guidance allowing for extensive investigations at little cost. We report the results of theoretically determined reaction yields for (99m)Tc and other radioactive isotopes created when natural and enriched molybdenum targets are irradiated by protons. The cross-section calculations were performed using a computer program EMPIRE for the proton energy range 6-30 MeV. A computer graphical user interface for automatic calculation of production yields taking into account various reaction channels leading to the same final product has been created. The proposed approach allows us to theoretically estimate the amount of (99m)Tc and its ratio relative to (99g)Tc and other radioisotopes which must be considered reaction contaminants, potentially contributing to additional patient dose in diagnostic studies.

The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.

PubMed

Runge, Roswitha; Oehme, Liane; Kotzerke, Jörg; Freudenberg, Robert

2016-12-01

DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO). Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay. Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively. For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Measurement and Estimation of the 99Mo Production Yield by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Minato, Futoshi; Tsukada, Kazuaki; Sato, Nozomi; Watanabe, Satoshi; Saeki, Hideya; Kawabata, Masako; Hashimoto, Shintaro; Nagai, Yasuki

2017-11-01

We, for the first time, measured the yield of 99Mo, the mother nuclide of 99mTc used in nuclear medicine diagnostic procedures, produced by the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The neutrons with a continuous energy spectrum from the thermal energy up to about 40 MeV were provided by the C(d,n) reaction with 40 MeV deuteron beams. It was proved that the 99Mo yield agrees with that estimated by using the latest data on neutrons from the C(d,n) reaction and the evaluated cross section of the 100Mo(n,2n)99Mo reaction given in the Japanese Evaluated Nuclear Data Library. On the basis of the agreement, a systematic calculation was carried out to search for an optimum condition that enables us to produce as much 99Mo as possible with a good 99Mo/100Mo value from an economical point of view. The calculated 99Mo yield from a 150 g 100MoO3 sample indicated that about 30% of the demand for 99Mo in Japan can be met with a single accelerator capable of 40 MeV, 2 mA deuteron beams. Here, by referring to an existing 18F-fluorodeoxyglucose (FDG) distribution system we assumed that 99mTc radiopharmaceuticals formed after separating 99mTc from 99Mo can be delivered to hospitals from a radiopharmaceutical company within 6 h. The elution of 99mTc from 99Mo twice a day would meet about 50% of the demand for 99Mo.

Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).

PubMed

Carta, Davide; Jentschel, Christian; Thieme, Stefan; Salvarese, Nicola; Morellato, Nicolò; Refosco, Fiorenzo; Ruzza, Paolo; Bergmann, Ralf; Pietzsch, Hans-Jurgen; Bolzati, Cristina

2014-08-01

Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M=(99m)Tc and (188)Re). This study aims to compare the capability and the efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+) complexes (cys~=cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N(3-) donors and of the exchanging ligand, was determined. For (99m)Tc, data clearly show that HDTCZ is the most efficient donor of N(3-); however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [(99m)Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG600-DTCZ or HDTCZ are used in N(3-) donation, high amounts of the exchanging ligand (10(-4)M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [(188)Re(N)] preparation (0.050mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [(188)Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation and evaluation of model-based crosstalk compensation method in simultaneous /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT

NASA Astrophysics Data System (ADS)

Song, X.; Frey, E. C.; Wang, W. T.; Du, Y.; Tsui, B. M. W.

2004-02-01

Simultaneous acquisition of /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT has several potential advantages, but the image quality is degraded by crosstalk between the Tc and Tl data. We have previously developed a crosstalk model that includes estimates of the downscatter and Pb X-ray for use in crosstalk compensation. In this work, we validated the model by comparing the crosstalk from /sup 99m/Tc to the Tl window calculated using a combination of the SimSET-MCNP Monte Carlo simulation codes. We also evaluated the model-based crosstalk compensation method using both simulated data from the 3-D MCAT phantom and experimental data from a physical phantom with a myocardial defect. In these studies, the Tl distributions were reconstructed from crosstalk contaminated data without crosstalk compensation, with compensation using the model-based crosstalk estimate, and with compensation using the known true crosstalk, and were compared with the Tl distribution reconstructed from uncontaminated Tl data. Results show that the model gave good estimates of both the downscatter photons and Pb X-rays in the simultaneous dual-isotopes myocardial perfusion SPECT. The model-based compensation method provided image quality that was significantly improved as compared to no compensation and was very close to that from the separate acquisition.

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

PubMed

Eising, E G; Farahati, J; Bier, D; Knust, E J; Reiners, C

1995-02-01

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT

NASA Astrophysics Data System (ADS)

Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

2015-09-01

Due to the limited spatial resolution, partial volume effect has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with 99mTc-tetrofosmin, a myocardial perfusion agent, and 99mTc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of 99mTc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both 99mTc-tetrofosmin perfusion imaging and 99mTc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly for low count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications.

Gallium-68 EDTA PET/CT for Renal Imaging.

PubMed

Hofman, Michael S; Hicks, Rodney J

2016-09-01

Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

[Situation of supply and boom of PET imaging: what is the future for technetium-99m in nuclear medicine?].

PubMed

Maia, S; Ayachi Hatit, N; Paycha, F

2011-05-01

Molecular imaging has shown its interest in the diagnosis, staging and therapy monitoring of many diseases, especially in the field of cancer. This imaging modality can detect non-invasively early molecular changes specific to these diseases. Its expansion includes two aspects linked firstly with the advanced techniques of imaging modalities and secondly with the development of tracers as radio pharmaceuticals for imaging new molecular targets. Technetium-99m ((99m)Tc), because of its physical characteristics, its widespread availability and low cost, is the most used radionuclide in molecular imaging with the technique of single photon emission computed tomography (SPECT). Nevertheless, the current difficulty concerning the supply and the great interest of Positron Emission Tomography (PET), the "competitor" imaging modality-using molecules labelled with fluorine-18 ((18)F), legitimates the question about the future of (99m)Tc, its supremacy and the emergence of new tracer labelled with (99m)Tc. Focusing on the actual and future supply situation, the place of SPECT imaging in nuclear medicine, as well as the development of new molecules labelled with (99m)Tc is necessary to show that this radionuclide will remain essential for the speciality in the next years. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to background ratio, on MAA stability and reuse after its first preparation.

PubMed

Malhotra, Anshoo; Kumar, Pardeep; Sharma, Sarika; Dhawan, Davinder K

2010-01-01

The present study was designed to develop stable and economically competitive radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled with (99m)Tc pertechnetate by following the standard protocol which included incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every experiment. The rats were injected intravenously with (99m)Tc MAA and were sacrificed after 10 min to study its distribution in the lungs and other non target tissues using gamma ray spectrometer. This standard protocol was further experimented upon in order to achieve high target to non target ratio. Different formulations were prepared by incubating them at 80 degrees for different incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest target to non target ratio. Another group of rats that received the above formulation were sacrificed after two additional time intervals of 5 and 15 min. The target to non target ratio was high in animals sacrificed after 5 min of injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for different time durations 1, 2 and 9 days were also evaluated for their ability to be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept for 9 days showed the best target to non-target ratio. The present study suggests that MAA once prepared can be reused following labeling with (99m)Tc even after 9 days of storage with better target to non target ratio as compared to storage timer period of 1 and 2 days.

99mTc 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

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

PubMed

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

2002-02-01

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

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

PubMed Central

Pfannkuchen, Nina; Meckel, Marian; Bergmann, Ralf; Bachmann, Michael; Bal, Chandrasekhar; Sathekge, Mike; Mohnike, Wolfgang; Baum, Richard P.; Rösch, Frank

2017-01-01

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties. PMID:28524118

Glucagon-Like Peptide-1 Receptor Imaging with [Lys (40) (Ahx-HYNIC- (99 m) Tc/EDDA)NH 2 ]-Exendin-4 for the Diagnosis of Recurrence or Dissemination of Medullary Thyroid Cancer: A Preliminary Report.

PubMed

Pach, D; Sowa-Staszczak, A; Jabrocka-Hybel, A; Stefańska, A; Tomaszuk, M; Mikołajczak, R; Janota, B; Trofimiuk-Müldner, M; Przybylik-Mazurek, E; Hubalewska-Dydejczyk, A

2013-01-01

Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22-74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent.

Glucagon-Like Peptide-1 Receptor Imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-Exendin-4 for the Diagnosis of Recurrence or Dissemination of Medullary Thyroid Cancer: A Preliminary Report

PubMed Central

Pach, D.; Sowa-Staszczak, A.; Jabrocka-Hybel, A.; Stefańska, A.; Tomaszuk, M.; Mikołajczak, R.; Janota, B.; Trofimiuk-Müldner, M.; Przybylik-Mazurek, E.; Hubalewska-Dydejczyk, A.

2013-01-01

Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22–74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent. PMID:23606839

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.

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.

Study of axial mixing, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column using radiotracer technique.

PubMed

Ghiyas Ud Din; Imran Rafiq Chughtai; Hameed Inayat, Mansoor; Hussain Khan, Iqbal

2009-01-01

Axial mixing, holdup and slip velocity of dispersed phase which are parameters of fundamental importance in the design and operation of liquid-liquid extraction pulsed sieve plate columns have been investigated. Experiments for residence time distribution (RTD) analysis have been carried out for a range of pulsation frequency and amplitude in a liquid-liquid extraction pulsed sieve plate column with water as dispersed and kerosene as continuous phase using radiotracer technique. The column was operated in emulsion region and (99m)Tc in the form of sodium pertechnetate eluted from a (99)Mo/(99m)Tc generator was used to trace the dispersed phase. Axial dispersed plug flow model with open-open boundary condition and two points measurement method was used to simulate the hydrodynamics of dispersed phase. It has been observed that the axial mixing and holdup of dispersed phase increases with increase in pulsation frequency and amplitude until a maximum value is achieved while slip velocity decreases with increase in pulsation frequency and amplitude until it approaches a minimum value. Short lived and low energy radiotracer (99m)Tc in the form of sodium pertechnetate was found to be a good water tracer to study the hydrodynamics of a liquid-liquid extraction pulsed sieve plate column operating with two immiscible liquids, water and kerosene. Axial dispersed plug flow model with open-open boundary condition was found to be a suitable model to describe the hydrodynamics of dispersed phase in the pulsed sieve plate extraction column.

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.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

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

PubMed

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

2016-05-01

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

MOEX: Solvent extraction approach for recycling enriched 98Mo/ 100Mo material

DOE PAGES

Tkac, Peter; Brown, M. Alex; Momen, Abdul; ...

2017-03-20

Several promising pathways exist for the production of 99Mo/ 99mTc using enriched 98Mo or 100Mo. Use of Mo targets require a major change in current generator technology, and the necessity for an efficient recycle pathway to recover valuable enriched Mo material. High recovery yields, purity, suitable chemical form and particle size are required. Results on the development of the MOEX– molybdenum solvent extraction – approach to recycle enriched Mo material are presented. Furthermore, the advantages of the MOEX process are very high decontamination factors from potassium and other elements, high throughput, easy scalability, automation, and minimal waste generation.

MOEX: Solvent extraction approach for recycling enriched 98Mo/ 100Mo material

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

Tkac, Peter; Brown, M. Alex; Momen, Abdul

Several promising pathways exist for the production of 99Mo/ 99mTc using enriched 98Mo or 100Mo. Use of Mo targets require a major change in current generator technology, and the necessity for an efficient recycle pathway to recover valuable enriched Mo material. High recovery yields, purity, suitable chemical form and particle size are required. Results on the development of the MOEX– molybdenum solvent extraction – approach to recycle enriched Mo material are presented. Furthermore, the advantages of the MOEX process are very high decontamination factors from potassium and other elements, high throughput, easy scalability, automation, and minimal waste generation.

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

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

PubMed

Pina, Géraldine; Dubois, Séverine; Murat, Arnaud; Berger, Nicole; Niccoli, Patricia; Peix, Jean-Louis; Cohen, Régis; Guillausseau, Claudine; Charrie, Anne; Chabre, Olivier; Cornu, Catherine; Borson-Chazot, Françoise; Rohmer, Vincent

2013-03-01

To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. Multicentric prospective study. A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test. © 2012 Blackwell Publishing Ltd.

Wear measurement using radioactive tracer technique based on proton, deuteron and α-particle induced nuclear reactions on molybdenum

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.

2012-11-01

Excitation functions of light ion induced nuclear reactions on natural molybdenum have been studied in the frame of a systematic investigation of charged particle induced nuclear reactions on metals for various applications. Excitation functions of 93,94g,94m,95g,95m,96,99mTc, 90,93m,99Mo, 90,91m,92m,95m,95g,96Nb and 88,89Zr were measured up to 50 MeV deuteron energy Tárkányi et al., 2012 [1], 93m,93g,94m,94g,95m,95g,96g,99mTc, 90,93m,99Mo, 90,92m,95m,95g,96Nb and 88,89Zr were measured up to 40 MeV proton energy Tárkányi et al., 2012 [2] and 93m,93g,94m,94g,95m,95g,96g,99mTc, 93m,99Mo, 90Nb, 94,95,97,103Ru and 88Zr were measured up to 40 MeV alpha energy Ditrói et al., 2012 [3] by using the stacked foil technique and activation method. The results for 3He induced reactions on natural Mo were taken from the literature Comparetto and Qaim, 1980 [4]. According to their half-lives, from the above listed radionuclides the 95m,96Tc, 91m,92m,95m,95gNb, 99Mo, 103,97Ru and 88Zr are suitable candidates for wear measurement by using thin layer activation (TLA) method. The goal of this work was to determine the necessary nuclear data for TLA of the above radionuclides and to prove their applicability for wear measurements.

High-Resolution 4D Imaging of Technetium Transport in Porous Media using Preclinical SPECT-CT

NASA Astrophysics Data System (ADS)

Dogan, M.; DeVol, T. A.; Groen, H.; Moysey, S. M.; Ramakers, R.; Powell, B. A.

2015-12-01

Preclinical SPECT-CT (single-photon emission computed tomography with integrated X-ray computed tomography) offers the potential to quantitatively image the dynamic three-dimensional distribution of radioisotopes with sub-millimeter resolution, overlaid with structural CT images (20-200 micron resolution), making this an attractive method for studying transport in porous media. A preclinical SPECT-CT system (U-SPECT4CT, MILabs BV. Utrecht, The Netherlands) was evaluated for imaging flow and transport of 99mTc (t1/2=6hrs) using a 46,5mm by 156,4mm column packed with individual layers consisting of <0.2mm diameter silica gel, 0.2-0.25, 0.5, 1.0, 2.0, 3.0, and 4.0mm diameter glass beads, and a natural soil sample obtained from the Savannah River Site. The column was saturated with water prior to injecting the 99mTc solution. During the injection the flow was interrupted intermittently for 10 minute periods to allow for the acquisition of a SPECT image of the transport front. Non-uniformity of the front was clearly observed in the images as well as the retarded movement of 99mTc in the soil layer. The latter is suggesting good potential for monitoring transport processes occurring on the timescale of hours. After breakthrough of 99mTc was achieved, the flow was stopped and SPECT data were collected in one hour increments to evaluate the sensitivity of the instrument as the isotope decayed. Fused SPECT- CT images allowed for improved interpretation of 99mTc distributions within individual pore spaces. With ~3 MBq remaining in the column, the lowest activity imaged, it was not possible to clearly discriminate any of the pore spaces.

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

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.

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

Nurse exposure doses resulted from bone scintigraphy patient

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

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

Role of scintigraphy in urinary tract infection

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

Conway, J.J.

1988-10-01

There is controversy regarding the role of radiological imaging for urinary tract infection (UTI). The gold standard has been the intravenous pyelogram (IVP). Yet, the IVP has a very limited value with only about 25% of children with pyelonephritis demonstrating abnormalities. Ultrasound (US) has recently been advocated as a replacement for the poorly sensitive and poorly specific IVP. However, comparative studies between US and IVP indicate only an equivalent sensitivity and specificity. Cortical scintigraphy with Technetium-99m glucoheptonate (99mTc GH) or 99mTc dimercaptosuccinic acid (99mTc DMSA) has also been advocated as a means of differentiating parenchymal (pyelonephritis) from nonparenchymal (lower UTI)more » involvement in UTI. The clinical presentation may be misleading especially in the infant and child in whom an elevated temperature, flank pain, shaking chills, or an elevated sedimentation rate are often lacking. The clinician attempts to localize the site of infection for it has a direct bearing upon the therapy. A collecting system infection can often be eradicated with a single oral dose of an appropriate antibiotic, whereas renal parenchymal involvement requires IV therapy for an extended interval. Cortical scintigraphy can localize the site of infection with a high degree of accuracy. Recent studies report a sensitivity of 86% and specificity of 81% of pyelonephritis. This is in contrast to the IVP with a sensitivity of only 24% and US with a sensitivity of only 42%. The scintigraphic appearance of parenchymal infection of the kidney is a spectrum of minimal to gross defects reflecting the degree of histologic involvement that spans from a mild infection to frank abscess. Cortical scintigraphy can be used to monitor the evolution of scarring following infection. Cortical scintigraphy with 99mTc DMSA or 99mTc GH is the method of choice for the initial evaluation of UTI. 37 references.« less

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

PubMed

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

2015-03-21

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

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

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.

Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.

PubMed

Portilho, Filipe Leal; Helal-Neto, Edward; Cabezas, Santiago Sánchez; Pinto, Suyene Rocha; Dos Santos, Sofia Nascimento; Pozzo, Lorena; Sancenón, Félix; Martínez-Máñez, Ramón; Santos-Oliveira, Ralph

2018-02-27

Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.

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.

GATE Simulations of Small Animal SPECT for Determination of Scatter Fraction as a Function of Object Size

NASA Astrophysics Data System (ADS)

Konik, Arda; Madsen, Mark T.; Sunderland, John J.

2012-10-01

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

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.

Differences between the macroscopic and tracer level chemistry of rhenium and technetium: contrasting cage isomerisation behaviour of Re(I) and Tc(I) carborane complexes.

PubMed

Armstrong, Andrea F; Valliant, John F

2010-09-21

Carboranes form stable complexes with the [M(CO)(3)](+) (M = (99m)Tc, Re) core and are viable ligands for the development of targeted radiopharmaceuticals. (99m)Tc-carborane complexes were found to exhibit substantially different 1,2-->1,7 cage isomerisation behaviour than their Re counterparts, challenging the validity of the routine use of rhenium as a surrogate for the development of technetium-99m based molecular imaging agents.

Use of {sup 99m}Tc 2-methoxyisobutyl isonitrile in minimally invasive radioguided surgery in patients with primary hyperparathyroidism: A narrative review of the current literature

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

Denmeade, Kristie A; Constable, Chris; Reed, Warren M

The use of technetium-99m 2-methoxyisobutyl isonitrile ({sup 99m}Tc MIBI) for assistance in minimally invasive radioguided surgery (MIRS) is growing in popularity as a safe, effective, and proficient technique used for parathyroidectomy in primary hyperparathyroidism (PHPT) treatment. Previously, the preferred treatment for PHPT was bilateral neck exploration (BNE), a very invasive, costly, and lengthy procedure. However, as a large majority (80–85% of cases of PHPT) are attributed to a single parathyroid adenoma (PA), a simpler more direct technique such as MIRS is a far better option. The following article is an exploration of the current literature concerning varied protocols utilizing {supmore » 99m}Tc MIBI for assistance in MIRS for patients undergoing treatment of PHPT. This technique boasts many advantageous outcomes for patients suffering from PHPT. These include a reduction in cost, operating time, and patient recovery; less evidence of post-surgical hypocalcaemia, less pain, and complications; superior cosmetic results; same-day discharge; and the possibility of local anaesthesia which is particularly beneficial in elderly patients. Better outcomes for patients with deep or ectopic PAs, reduced intra-operative complications, and improved cosmetic outcomes for patients who have previously undergone thyroid and/or parathyroid surgery are also advantageous. Of the literature reviewed it was also found that no patients suffered any major surgical complications such as laryngeal nerve palsy or permanent hypoparathyroidism using {sup 99m}Tc MIBI for assistance in MIRS.« less

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.

[Shielding effect of clinical X-ray protector and lead glass against annihilation radiation and gamma rays of 99mTc].

PubMed

Fukuda, Atsushi; Koshida, Kichiro; Yamaguchi, Ichiro; Takahashi, Masaaki; Kitabayashi, Keitarou; Matsubara, Kousuke; Noto, Kimiya; Kawabata, Chikako; Nakagawa, Hiroto

2004-12-01

Various pharmaceutical companies in Japan are making radioactive drugs available for positron emission tomography (PET) in hospitals without a cyclotron. With the distribution of these drugs to hospitals, medical check-ups and examinations using PET are expected to increase. However, the safety guidelines for radiation in the new deployment of PET have not been adequately improved. Therefore, we measured the shielding effect of a clinical X-ray protector and lead glass against annihilation radiation and gamma rays of (99m)Tc. We then calculated the shielding effect of a 0.25 mm lead protector, 1 mm lead, and lead glass using the EGS4 (Electron Gamma Shower Version 4) code. The shielding effects of 22-mm lead glass against annihilation radiation and gamma rays of (99m)Tc were approximately 31.5% and 93.3%, respectively. The clinical X-ray protector against annihilation radiation approximately doubled the skin-absorbed dose.

Dual-Labeled Near-Infrared/99mTc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells

PubMed Central

Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

2016-01-01

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m (99mTc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with 99mTc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner. PMID:27399687

Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells.

PubMed

Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

2016-07-07

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner.

Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

PubMed

Dias, Carla Roberta; Jeger, Simone; Osso, João Alberto; Müller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

2011-01-01

The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology). The native format of the antibody (RTX(wt)) as well as a reduced form (RTX(red)) was labeled with (99m)Tc/(188)Re(CO)(3). The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. The radiolabeling efficiency and kinetics of RTX(red) were superior to that of RTX(wt) ((99m)Tc: 98% after 3 h for RTX(red) vs. 70% after 24 h for RTX(wt)). (99m)Tc(CO)(3)-RTX(red) was used without purification for in vitro and in vivo studies whereas (188)Re(CO)(3)-RTX(red) was purified to eliminate free (188)Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 °C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of (99m)Tc(CO)(3)-RTX(red) but not with pre-purified (188)Re(CO)(3)-RTX(red). Both conjugates revealed high binding affinity to the CD20 antigen (K(d) = 5-6 nM). Tumor uptake of (188)Re(CO)(3)-RTX(red) was 2.5 %ID/g and 0.8 %ID/g for (99m)Tc(CO)(3)-RTX(red) 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for (99m)Tc(CO)(3)-RTX(red) and for (188)Re(CO)(3)-RTX(red) 0.5 and 0.5 (24 h pi). Rituximab could be directly and stably labeled with the matched pair (99m)Tc/(188)Re using the IsoLink technology under retention of the biological activity. Labeling kinetics and yields need further improvement for potential routine application in radioimmunodiagnosis and therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

The bone scan.

PubMed

Brenner, Arnold I; Koshy, June; Morey, Jose; Lin, Cheryl; DiPoce, Jason

2012-01-01

Bone imaging continues to be the second greatest-volume nuclear imaging procedure, offering the advantage of total body examination, low cost, and high sensitivity. Its power rests in the physiological uptake and pathophysiologic behavior of 99m technetium (99m-Tc) diphosphonates. The diagnostic utility, sensitivity, specificity, and predictive value of 99m-Tc bone imaging for benign conditions and tumors was established when only planar imaging was available. Currently, nearly all bone scans are performed as a planar study (whole-body, 3-phase, or regional), with the radiologist often adding single-photon emission computed tomography (SPECT) imaging. Here we review many current indications for planar bone imaging, highlighting indications in which the planar data are often diagnostically sufficient, although diagnosis may be enhanced by SPECT. (18)F sodium fluoride positron emission tomography (PET) is also re-emerging as a bone agent, and had been considered interchangeable with 99m-Tc diphosphonates in the past. In addition to SPECT, new imaging modalities, including (18)F fluorodeoxyglucose, PET/CT, CT, magnetic resonance, and SPECT/CT, have been developed and can aid in evaluating benign and malignant bone disease. Because (18)F fluorodeoxyglucose is taken up by tumor cells and Tc diphosphonates are taken up in osteoblastic activity or osteoblastic healing reaction, both modalities are complementary. CT and magnetic resonance may supplement, but do not replace, bone imaging, which often detects pathology before anatomic changes are appreciated. We also stress the importance of dose reduction by reducing the dose of 99m-Tc diphosphonates and avoiding unnecessary CT acquisitions. In addition, we describe an approach to image interpretation that emphasizes communication with referring colleagues and correlation with appropriate history to significantly improve our impact on patient care. Copyright © 2012 Elsevier Inc. All rights reserved.

Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

PubMed Central

Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

2016-01-01

INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

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

Harnsberger, H.R.; Datz, F.L.; Knochel, J.Q.

A patient with postpolycythemic myeloid metaplasia developed an enlarging abdominal mass documented on TCT scanning. To distinguish between lymphoma and extramedullary hematopoiesis, marrow elements were imaged with /sup 111/In chloride and /sup 99m/Tc sulfur colloid. Because the mass failed to accumulate either tracer, a presumptive diagnosis of lymphoma was made and exploratory surgery was performed. The excised mass was found to consist of enlarged lymph nodes containing extramedullary hematopoiesis. Caution should be exercised in the use of /sup 111/In or /sup 99m/Tc SC bone-marrow scans to diagnose sites of extramedullary hematopoiesis.

Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

NASA Astrophysics Data System (ADS)

Qin, Zhengtao

Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and 99mTc. Chapter 5 introduces a 68Ga metal chelating bioorthogonal tetrazine dextran probe for multistep imaging of a colon cancer. Chapter 6 presents the synthesis and in vivo evaluation of a Hepatocellular Carcinoma targeting PET probe 68Ga-Insulin-Dextran. Chapter 7 discusses a novel method to prepare silicon nanoparticles with great yield and size control. The last chapter 8 concludes all probes developed in this thesis and their clinical relevance.

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.

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

NASA Astrophysics Data System (ADS)

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

2015-11-01

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

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 scintigraphic patterns can establish the preoperative diagnosis of vascular orbital tumors such as cavernous hemangioma, adult-type lymphangioma, and hemangiopericytoma.

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 has a focus on coordination and labeling chemistry, but biological results are briefly summarized as well. The last (and shortest) section finally intends to give a (subjective) outlook for the future role of 99mTc-based radiopharmaceuticals. Critical comments are spread over the whole article but are concentrated in this section. Despite the increasing competition of diagnostic radiopharmacy by other commonly applied methods in medicine such as magnetic resonance imaging (MRI) or ultrasound, the authors are convinced that 99mTc will play a key role also in future if novel approaches are added and the requirements from chemistry biology and the market considered in research to a stronger extent.

The standardization methods of radioactive sources (125I, 131I, 99mTc, and 18F) for calibrating nuclear medicine equipment in Indonesia

NASA Astrophysics Data System (ADS)

Wurdiyanto, G.; Candra, H.

2016-03-01

The standardization of radioactive sources (125I, 131I, 99mTc and 18F) to calibrate the nuclear medicine equipment had been carried out in PTKMR-BATAN. This is necessary because the radioactive sources used in the field of nuclear medicine has a very short half-life in other that to obtain a quality measurement results require special treatment. Besides that, the use of nuclear medicine techniques in Indonesia develop rapidly. All the radioactive sources were prepared by gravimetric methods. Standardization of 125I has been carried out by photon- photon coincidence methods, while the others have been carried out by gamma spectrometry methods. The standar sources are used to calibrate a Capintec CRC-7BT radionuclide calibrator. The results shows that calibration factor for Capintec CRC-7BT dose calibrator is 1,03; 1,02; 1,06; and 1,04 for 125I, 131I, 99mTc and 18F respectively, by about 5 to 6% of the expanded uncertainties.

Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer.

PubMed

Yu, Xinhe; Wu, Yue; Liu, Hao; Gao, Liquan; Sun, Xianlei; Zhang, Chenran; Shi, Jiyun; Zhao, Huiyun; Jia, Bing; Liu, Zhaofei; Wang, Fan

2016-05-01

To assess the potential utility of an integrin αvβ3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvβ3 on the activated hepatic stellate cells, and the integrin αvβ3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001). (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Development of a patient-specific dosimetry estimation system in nuclear medicine examination

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

Lin, H. H.; Dong, S. L.; Yang, H. J.

2011-07-01

The purpose of this study is to develop a patient-specific dosimetry estimation system in nuclear medicine examination using a SimSET-based Monte Carlo code. We added a dose deposition routine to store the deposited energy of the photons during their flights in SimSET and developed a user-friendly interface for reading PET and CT images. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The S values for {sup 99m}Tc, {sup 18}F and {sup 131}I obtained by the system were compared to those from the MCNP4C code and OLINDA. The ratios of S values computed by thismore » system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which are comparable to that obtained from MCNP4C code (0.94 to 1.20). The average ratios of S value were 0.99{+-}0.04, 1.03{+-}0.05, and 1.00{+-}0.07 for isotopes {sup 131}I, {sup 18}F, and {sup 99m}Tc, respectively. The simulation time of SimSET was two times faster than MCNP4C's for various isotopes. A 3D dose calculation was also performed on a patient data set with PET/CT examination using this system. Results from the patient data showed that the estimated S values using this system differed slightly from those of OLINDA for ORNL phantom. In conclusion, this system can generate patient-specific dose distribution and display the isodose curves on top of the anatomic structure through a friendly graphic user interface. It may also provide a useful tool to establish an appropriate dose-reduction strategy to patients in nuclear medicine environments. (authors)« less

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.

[Importance of parathyroid SPECT and 99mTc scintigraphy, and of clinical, laboratorial, ultrasonographic and citologic correlation in the pre-operative localization of the parathyroid adenoma - pictorial assay].

PubMed

Oliveira, Marco Antônio Condé de; Maeda, Sérgio Setsuo; Dreyer, Patrícia; Lobo, Alberto; Andrade, Victor Piana de; Hoff, Ana O; Biscolla, Rosa Paula Mello; Smanio, Paola; Brandão, Cynthia M A; Vieira, José G

2010-06-01

In patients with primary hyperparathyroidism, candidates for surgical intervention, the parathyroid pre-operative localization is of fundamental importance in planning the appropriate surgical approach. The additional acquisition of SPECT and Technetium-99m images, during parathyroid scintigraphy with Sestamibi, is not common practice. Usually, only planar image acquisition, 15 minutes prior and 2 hours after radiopharmaceutical administration, is performed. In our experience, the complete protocol in parathyroid scintigraphy increases the accuracy of pre-operative parathyroid localization. The complete utilization of all available nuclear medicine methods (SPECT e 99mTc) and image interpretation in a multidisciplinary context can improve the accuracy of parathyroid scintigraphy.

Attenuation of radionuclide activity by metal-cup arthroplasties

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

Rosenthall, L.; Rosenthall, S.

1985-04-01

The half-value layers of stainless steel, bone cement, and polyethylene were measured for /sup 99m/Tc, /sup 67/Ga, /sup 111/In, and /sup 201/TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in /sup 99m/Tc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. /sup 67/Ga, using the 184 and 300 keV peaks, and /sup 111/In have greater half-value layers than /sup 99m/Tc and are subject to less attenuation bymore » the metallic cup.« less

Direct Production of 99mTc via 100Mo(p,2n) on Small Medical Cyclotrons

NASA Astrophysics Data System (ADS)

Schaffer, P.; Bénard, F.; Bernstein, A.; Buckley, K.; Celler, A.; Cockburn, N.; Corsaut, J.; Dodd, M.; Economou, C.; Eriksson, T.; Frontera, M.; Hanemaayer, V.; Hook, B.; Klug, J.; Kovacs, M.; Prato, F. S.; McDiarmid, S.; Ruth, T. J.; Shanks, C.; Valliant, J. F.; Zeisler, S.; Zetterberg, U.; Zavodszky, P. A.

From the efforts of a number of Canadian institutions and private industry collaborations, direct production of 99mTc using medical cyclotrons has recently been advanced from a 1970's academic exercise to a commercial, economically viable solution for regional production. Using GE PETtrace 880 machines our team has established preliminary saturated yields of 2.7 GBq/μA, translating to approximately 174 GBq after a 6 hour irradiation. The team is in the process of assessing the accuracy and reliability of this production value with a goal of optimizing yields by up to 50%.

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.

Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis

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

Vitti, R.A.; Meyers, F.; Knight, L.C.

1989-11-01

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of (99mTc)5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending,more » transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of (99mTc)5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume (99mTc)5-ASA enemas reliably reach the area of inflammation.« less

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

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

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

1994-03-01

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

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

PubMed

Mei, Lei; Wang, Yue; Chu, Taiwei

2012-12-01

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

Real-time gamma imaging of technetium transport through natural and engineered porous materials for radioactive waste disposal.

PubMed

Corkhill, Claire L; Bridge, Jonathan W; Chen, Xiaohui C; Hillel, Phil; Thornton, Steve F; Romero-Gonzalez, Maria E; Banwart, Steven A; Hyatt, Neil C

2013-12-03

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of (99)Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in (99m)Tc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ~20 MBq (99m)Tc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min(-1). Changes in calibrated mass distribution of (99m)Tc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection-dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that (99)Tc in the pertechnetate form (Tc(VII)O4(-)) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments.

Real-Time Gamma Imaging of Technetium Transport through Natural and Engineered Porous Materials for Radioactive Waste Disposal

PubMed Central

2013-01-01

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of 99Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in 99mTc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ∼20 MBq 99mTc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min–1. Changes in calibrated mass distribution of 99mTc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection–dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that 99Tc in the pertechnetate form (Tc(VII)O4–) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments. PMID:24147650

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

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.

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

PubMed Central

Giblin, Michael F.; Wang, Nannan; Hoffman, Timothy J.; Jurisson, Silvia S.; Quinn, Thomas P.

1998-01-01

α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties. PMID:9788997

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

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.

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.

Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks

PubMed Central

Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

2016-01-01

Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network. PMID:27936011

Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks.

PubMed

Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

2016-01-01

Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network.

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

PubMed

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

2012-11-20

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

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m.

PubMed

Fuscaldi, Leonardo Lima; Dos Santos, Daniel Moreira; Pinheiro, Natália Gabriela Silva; Araújo, Raquel Silva; de Barros, André Luís Branco; Resende, Jarbas Magalhães; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento

2016-01-01

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with (99m)Tc. Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with (99m)Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 (.) 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol(.)L(-1) (S. aureus) and 10.10 μmol(.)L(-1) (E. coli). Thus, only the latter was radiolabeled with (99m)Tc. The radiochemical purity analysis of LyeTx I-K-HYNIC-(99m)Tc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2 (.) 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n = 3). However, RP-HPLC data suggested (99m)Tc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Investigation of activation cross section data of alpha particle induced nuclear reaction on molybdenum up to 40 MeV: Review of production routes of medically relevant 97,103Ru

NASA Astrophysics Data System (ADS)

Tárkányi, F.; Hermanne, A.; Ditrói, F.; Takács, S.; Ignatyuk, A.

2017-05-01

The main goals of this investigations were to expand and consolidate reliable activation cross-section data for the natMo(α,x) reactions in connection with production of medically relevant 97,103Ru and the use of the natMo(α,x)97Ru reaction for monitoring beam parameters. The excitation functions for formation of the gamma-emitting radionuclides 94Ru, 95Ru, 97Ru, 103Ru, 93mTc, 93gTc(m+), 94mTc, 94gTc, 95mTc, 95gTc, 96gTc(m+), 99mTc, 93mMo, 99Mo(cum), 90Nb(m+) and 88Zr were measured up to 40 MeV alpha-particle energy by using the stacked foil technique and activation method. Data of our earlier similar experiments were re-evaluated and resulted in corrections on the reported results. Our experimental data were compared with critically analyzed literature data and with the results of model calculations, obtained by using the ALICE-IPPE, EMPIRE 3.1 (Rivoli) and TALYS codes (TENDL-2011 and TENDL-2015 on-line libraries). Nuclear data for different production routes of 97Ru and 103Ru are compiled and reviewed.

Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom simulation study.

PubMed

Norberg, Pernilla; Olsson, Anna; Alm Carlsson, Gudrun; Sandborg, Michael; Gustafsson, Agnetha

2015-01-01

The amount of inhomogeneities in a (99m)Tc Technegas single-photon emission computed tomography (SPECT) lung image, caused by reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), is correlated to disease advancement. A quantitative analysis method, the CVT method, measuring these inhomogeneities was proposed in earlier work. To detect mild COPD, which is a difficult task, optimised parameter values are needed. In this work, the CVT method was optimised with respect to the parameter values of acquisition, reconstruction and analysis. The ordered subset expectation maximisation (OSEM) algorithm was used for reconstructing the lung SPECT images. As a first step towards clinical application of the CVT method in detecting mild COPD, this study was based on simulated SPECT images of an advanced anthropomorphic lung software phantom including respiratory and cardiac motion, where the mild COPD lung had an overall ventilation reduction of 5%. The best separation between healthy and mild COPD lung images as determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc was obtained using a low-energy high-resolution collimator (LEHR) and a power 6 Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four reconstruction updates and a small kernel size should be used when the whole lung is analysed, and for the reduced lung a greater number of updates and a larger kernel size are needed. A LEHR collimator and 125 (99m)Tc MBq together with an optimal combination of cutoff frequency, number of updates and kernel size, gave the best result. Suboptimal selections of either cutoff frequency, number of updates and kernel size will reduce the imaging system's ability to detect mild COPD in the lung phantom.

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](+).

{sup 99m}Tc DTPA aerosol clearances in the assessment of radiation injury top the lung

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

Halkar, R.K.; Raghab, A.; Higazi, E.

1994-05-01

In a prospective study, 36 patients with inoperable lung Ca. (sq. cells-24, adeno-5, largecell-2, unknown-5) underwent pre and post radiation {sup 99m}Tc DTPA aerosol clearance studies. The aim was to evaluate the value of aerosol clearance in the prediction of radiation injury to the regions other than the radiation field. Aerosol study was done using a commercially available nebulizer, dynamic images were obtained (30 sec/frame) in the posterior projection for a duration of 45 min. ROIs were drawn on upper, mid and lower zones on either lung, and time activity curves were generated. Using a linear fit, clearance half timemore » (t{sub 1/2}) was calculated, for all six curves. The difference between pre and post radiation (t{sub 1/2}) was compared to the clinical follow up of each patient and a difference of more than 15 minutes was considered positive. Of the 36 patients 12 had a t{sub 1/2} difference of more than 15 minutes. Of these 5 patients had radiation pulmonlitis and the remaining 7 had respiratory failure due to infection and uremia. 24 patients had a t{sub 1/2} difference of less than 15 minutes and their clinical follow-up did not reveal any evidence of pulmonary radiation injury during this period. The results indicate that the clearance of Tc-99m DTPA aerosols is effective for excluding radiation pulmonlitis.« less

MCNPX CALCULATIONS OF SPECIFIC ABSORBED FRACTIONS IN SOME ORGANS OF THE HUMAN BODY DUE TO APPLICATION OF 133Xe, 99mTc and 81mKr RADIONUCLIDES.

PubMed

Jovanovic, Z; Krstic, D; Nikezic, D; Ros, J M Gomez; Ferrari, P

2018-03-01

Monte Carlo simulations were performed to evaluate treatment doses with wide spread used radionuclides 133Xe, 99mTc and 81mKr. These different radionuclides are used in perfusion or ventilation examinations in nuclear medicine and as indicators for cardiovascular and pulmonary diseases. The objective of this work was to estimate the specific absorbed fractions in surrounding organs and tissues, when these radionuclides are incorporated in the lungs. For this purpose a voxel thorax model has been developed and compared with the ORNL phantom. All calculations and simulations were performed by means of the MCNP5/X code.

Monooxorhenium(V) complexes with 222-N2S2 MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation

PubMed Central

Demoin, Dustin Wayne; Dame, Ashley N.; Minard, William D.; Gallazzi, Fabio; Seickman, Gary L.; Rold, Tammy L.; Bernskoetter, Nicole; Fassbender, Michael E.; Hoffman, Timothy J.; Deakyne, Carol A.; Jurisson, Silvia S.

2016-01-01

Introduction Targeted radiotherapy using the bifunctional chelate approach with 186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications. Methods A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222- MAMA(N-6-Ahx-BBN(7-14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc and 186Re (carrier added and no carrier added), and evaluated in initial biological distribution studies. Results An IC50 value of 2.0 ± 0.7 nM for natReO-222-MAMA(N-6-Ahx-BBN(7-14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed little gastric uptake and blockable pancreatic uptake in normal mice. Conclusions The 186ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed stability in biological media, which indicates that the 222-N2S2 chelator is appropriate for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting. PMID:27694058

Feasibility study of medical isotope production at Sandia National Laboratories

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

Massey, C.D.; Miller, D.L.; Carson, S.D.

1995-12-01

In late 1994, Sandia National Laboratories in Albuquerque, New Mexico, (SNL/NM), was instructed by the Department of Energy (DOE) Isotope Production and Distribution Program (IPDP) to examine the feasibility of producing medically useful radioisotopes using the Annular Core Research Reactor (ACRR) and the Hot Cell Facility (HCF). Los Alamos National Laboratory (LANL) would be expected to supply the targets to be irradiated in the ACRR. The intent of DOE would be to provide a capability to satisfy the North American health care system demand for {sup 99}Mo, the parent of {sup 99m}Tc, in the event of an interruption in themore » current Canadian supply. {sup 99m}Tc is used in 70 to 80% of all nuclear medicine procedures in the US. The goal of the SNL/NM study effort is to determine the physical plant capability, infrastructure, and staffing necessary to meet the North American need for {sup 99}Mo and to identify and examine all issues with potential for environmental impact.« less

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Detection of Myocardial Ischemia-Reperfusion Injury Using a Fluorescent Near-Infrared Zinc(II)-Dipicolylamine Probe and 99mTc Glucarate

PubMed Central

wyffels, Leonie; Gray, Brian D.; Barber, Christy; Pak, Koon Y.; Forbes, Safiyyah; Mattis, Jeffrey A.; Woolfenden, James M.; Liu, Zhonglin

2012-01-01

A fluorescent zinc 2,2′-dipicolylamine coordination complex PSVue®794 (probe 1) is known to selectively bind to phosphatidylserine exposed on the surface of apoptotic and necrotic cells. In this study, we investigated the cell death targeting properties of probe 1 in myocardial ischemia-reperfusion injury. A rat heart model of ischemia-reperfusion was used. Probe 1, control dye, or 99mTc glucarate was intravenously injected in rats subjected to 30-minute and 5-minute myocardial ischemia followed by 2-hour reperfusion. At 90 minutes or 20 hours postinjection, myocardial uptake was evaluated ex vivo by fluorescence imaging and autoradiography. Hematoxylin-eosin and cleaved caspase-3 staining was performed on myocardial sections to demonstrate the presence of ischemiareperfusion injury and apoptosis. Selective accumulation of probe 1 could be detected in the area at risk up to 20 hours postinjection. Similar topography and extent of uptake of probe 1 and 99mTc glucarate were observed at 90 minutes postinjection. Histologic analysis demonstrated the presence of necrosis, but only a few apoptotic cells could be detected. Probe 1 selectively accumulates in myocardial ischemia-reperfusion injury and is a promising cell death imaging tool. PMID:22554483

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia

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

Rozen, P.; Gelfond, M.; Zaltzman, S.

1982-08-01

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with /sup 99m/Tc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent cine mode images of esophageal emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Synthesis of tripeptide derivatized cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes.

PubMed

Nadeem, Qaisar; Can, Daniel; Shen, Yunjun; Felber, Michael; Mahmood, Zaid; Alberto, Roger

2014-03-28

We describe the syntheses of half-sandwich complexes of the type [(η(5)-Cp(CONH-R))M(CO)3] with M = Re or (99m)Tc. The R group represents different tri-peptides (tpe) which display high binding affinities for oligopeptide transporters PEPT2. The (99m)Tc complexes were prepared directly from [(99m)Tc(OH2)3(CO)3](+) and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels-Alder reactions for the preparation of not only small molecules but also peptides carrying a [(η(5)-Cp)(99m)Tc(CO)3] tag. We synthesized the Diels-Alder product [(HCpCONH-tpe)2] from Thiele's acid [(η(5)-HCpCOOH)2] via double peptide coupling. The Re-complexes [(η(5)-CpCONH-tpe)Re(CO)3] were obtained by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as received from SPPS. The authenticity of the (99m)Tc-complexes is confirmed by chromatographic comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.

Targeting hypoxia in tumors using 2-nitroimidazoles with peptidic chelators for technetium-99m: effect of lipophilicity.

PubMed

Zhang, X; Su, Z F; Ballinger, J R; Rauth, A M; Pollak, A; Thornback, J R

2000-01-01

Tumor hypoxia is an important prognostic factor for response to therapy. Radiolabeled 2-nitroimidazoles have been used for imaging hypoxia, and the octanol/water partition coefficient (P) of these compounds appears to play a crucial role in their suitability for imaging. A series of 11 2-nitroimidazoles coupled to peptidic chelators for (99m)Tc with divergent P was developed and evaluated in an in vitro system. Two classes of N(3)S chelators were used: dialkyl-Gly-Ser-Cys-linker-2-nitroimidazole (Class I) and dialkyl-Gly-Lys(2-nitroimidazole)-Cys (Class II). The chelators were prepared by automated solid-phase peptide synthesis. Xanthine oxidase was able to reduce the 2-nitroimidiazole moiety on the ligands, but the rate of reduction varied 5-fold among the different chelators. The chelators were labeled by transchelation from [(99m)Tc]gluconate at temperatures between 22 and 100 degrees C. The reaction mixtures were analyzed by HPLC and their P values determined. The accumulation of each complex in suspension cultures of Chinese hamster ovary cells incubated under aerobic or extremely hypoxic conditions was determined. Radiochemical yields ranged from 5 to 80% for the 11 compounds. HPLC showed that some of the compounds formed two complexes with (99m)Tc, possibly syn and anti conformations with respect to the Tc=O bond. In general, the Class I chelators labeled more readily than the class II chelators. The P values of the (99m)Tc complexes varied from 0.0002 to 5 and were generally in accordance with predictions based on structure. There were also differences in P as a function of pH; the free acids had a lower P at pH 7.4 than at pH 2.0 due to ionization, whereas the amides did not show this effect. Accumulation levels in aerobic cells were related to P but varied over a narrow range. Four of the 11 compounds showed selective accumulation in hypoxic cells. The peptidic class of 2-nitroimidazoles, with flexible design and convenient solid-phase synthesis, deserves further study as agents for imaging hypoxia in tumors.

Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

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

Oliveira, P. A.; Santos, J. A. M., E-mail: joao.santos@ipoporto.min-saude.pt; Serviço de Física Médica do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto

2014-07-15

Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as{sup 99m}Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a carefulmore » analysis of the methodology, for the case of{sup 99m}Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using {sup 99m}Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for{sup 99m}Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides.« less

Assessment of effects of a Cordia salicifolia extract on the radiolabeling of blood constituents and on the morphology of red blood cells.

PubMed

Frydman, Jacques Natan Grinapel; Rocha, Vanessa Camara; Benarroz, Monica Oliveira; Rocha, Gabrielle Souza; Pereira, Márcia Oliveira; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2008-12-01

Effects of a Cordia salicifolia (porangaba) extract on the labeling of blood cells (BCs) with technetium-99m ((99m)Tc) and on the morphology of red BCs were evaluated. Labeling of cellular and molecular structures with (99m)Tc depends on a reducing agent. Some physical characteristics, as visible absorbance spectrum, electric conductivity, and refractive index of this porangaba extract, were also determined. Blood samples from Wistar rats were incubated with porangaba extract or with 0.9% NaCl (control). Labeling of blood constituents with (99m)Tc was performed. Plasma (P) and BCs, both soluble (SF-P and SF-BC) and insoluble (IF-P and IF-BC) fractions, were separated. The radioactivity in each fraction was counted, and the percentage of radioactivity incorporated (%ATI) was calculated. Blood smears were prepared, fixed, and stained, and the morphology of the red BCs was evaluated. Data showed an absorbance peak at 480 nm and electric conductibility and refractive index concentration-dependent. Porangaba extract decreased significantly (P < .05) the BC, IF-P, and IF-BC %ATI, and no modifications were verified on the shape of red BCs. Analysis of the results reveals that some physical parameters could be useful to aid in characterizing the extract studied. Moreover, it is possible that chemical compounds of this extract could have chelating/redox actions or be capable of binding to plasma and/or cellular proteins.

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

PubMed Central

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

2011-01-01

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

Re and 99mTc Tricarbonyl Probes for Target-Specific Detection of Melanoma and Sentinel Lymph Node

NASA Astrophysics Data System (ADS)

Morais, Mauricio da Silva

The work described in this thesis aimed at the development of M(I) (M = 99mTc, Re) specific probes for the detection of malignant melanoma and sentinel lymph node (SLN) through the in vivo targeting of membrane receptors. In the former case we have designed M(CO)3-complexes stabilized by tridentate chelators containing a pyrazolyl-diamine chelating unit (N,N,N donor atom set) and pendant alpha-melanocyte-stimulating hormone (alpha-MSH) derivatives for targeting the melanocortin receptor 1 (MC1R), which is overexpressed in melanotic and amelanotic human melanoma cells. (Abstract shortened by ProQuest.). None None None None None None None None None None None None None None None None None

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

Basinger, G.T.; McCullough, D.L.; McLaughlin, A.P.

Eleven patients with urologic cancer had an abnormal /sup 99m/Tc (technetium-99m) bone scan as the sole evidence of metastatic disease. Potentially curative therapy should not be withheld on the basis of a ''positive'' bone scan if such an area is accessible to selected bone biopsy and proves to be negative for tumor histologically.

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

PubMed

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

2016-01-01

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

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.

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.

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Thyroid uptake of (/sup 99m/Tc) pertechnetate during in vivo RBC labeling: incidental diagnosis of hypothyroidism

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

Holmes, K.A.; Ponto, J.A.

1981-09-01

Increased thyroid activity was incidentally observed during an in vivo labeled Tc-99m blood pool scan and subsequent evaluation resulted in a diagnosis of hypothyroidism. Alternate explanations of abnormal thyroid uptake on in vivo labeled blood pool scans were considered and are discussed briefly.

Extravasation of contrast material from vascular ectasia of the cecum detected with /sup 99m/Tc-pertechnetate

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

Tavormina, A.; Mousavi, A.; Gordon, D.H.

A case of vascular ectasia of the cecum is presented. The isotopic pattern did not differ from that of Meckel's diverticulum. The authors suggest that studies with /sup 99m/Tc may be helpful in screening for areas of pathology in cases of lower gastrointestinal bleeding.

A biokinetic model for systemic technetium in adult humans

DOE PAGES

Leggett, Richard Wayne; Giussani, Augusto

2015-04-10

The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T 1/2=2.1x10 5 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T 1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body formore » use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

(99m)Tc-EDDA/HYNIC-octreotate - a new radiotracer for detection and staging of NET: a case of metastatic duodenal carcinoid.

PubMed

Hubalewska-Dydejczyk, Alicja; Szybiński, Piotr; Fröss-Baron, Katarzyna; Mikolajczak, Renata; Huszno, Bohdan; Sowa-Staszczak, Anna

2005-01-01

Somatostatin receptor scintigraphy (SRS) has become a routine imaging method for the diagnostics of neuroendocrine tumours (NET). (99m)Tc-EDDA/HYNIC-octreotate (Polatom, Poland) is a new radiotracer with high affinity for SSTR2 and similar physiological biodistribution to (111)In-Octreoscan. We present a case of a 47-year-old man with disseminated duodenal carcinoid. The patient had been operated due to the tumour mass detected in pancreatic head area. Histopathology revealed carcinoid of the duodenal wall with local lymph node and liver metastases. The patient was qualified for chemotherapy stopped due to severe leucopenia. (99m)Tc EDDA/HYNIC-octreotate scintigraphy was performed for staging and to determine SSTR status of the tumour before planned 90Y-DOTATATE therapy. The multiple metastatic lesions were detected all over the body. The high quality images with high target/non target ratio were obtained. (99m)Tc-MDP scintigraphy confirmed multiple bone metastases. On the basis of SRS result the patient was qualified for 90Y-DOTA-TATE therapy. In conclusion, (99m)Tc EDDA/HYNIC-octreotate can be regarded as a promising tracer for staging and to determine SSTR status of NET.

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia: correlation with manometric measurements

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

Rozen, P.; Gelfond, M.; Zaltzman, S.

1982-08-01

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with /sup 99//sup m/Tc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent cine' mode images of esophagela emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Peptide Based Radiopharmaceuticals: Specific Construct Approach

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

Som, P; Rhodes, B A; Sharma, S S

1997-10-21

The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures).more » In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher density. The results have indicated good diagnostic potential for their use in this clinical situation, as an imaging agent to diagnose ischemic renal injury and differentiate from other causes. Very promising results were obtained with newly developed tuftsin related metallopeptides. A number of these peptides displayed high potency (nM range) in imaging infection. Antagonists were successfully used to image experimentally induced abscesses in rodents. One of the antagonists, termed 99mTc-RMT-1, was evaluated in rabbits and dogs for its applicability as infection/inflammation imaging agent. Both in dog and rabbit infection/inflammation models 99mTc-RMT-1 could be used for rapid scintigraphic diagnosis. A very high and rapid uptake was observed in both soft tissue and bone infection providing a good target to background contrast. The agent also allowed distinction between bone fracture and osteomyelitis. All these results warrant human clinical trials with 99mTc-RMT-1 which may help replace hazardous ex-vivo WBC labeling procedures that are current clincial modality for imaging infection foci.« less

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-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a′) compared to the peptide with the unmodified DPA chelate (9a′). In vivo biodistribution analysis of 9a′ and 10a′ showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a′ compared to predominantly hepatic accumulation for 9a′. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[MI(CO)3]+ complexes in future studies. PMID:24568284

99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands

PubMed Central

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C.P; Wood, Bradford; Carrasquillo, Jorge A.; Danthi, S. Narasimhan; Paik, Chang H.

2010-01-01

Objectives The aim of this research was to synthesize radiolabeled peptidomimetic integrin αvβ3 antagonist with 99mTc for rapid targeting of integrin αvβ3 receptors in tumor to produce a high tumor to background ratio. Methods The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-β-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with 99mTc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N′-diacetic acid (EDDA) as the co-ligand. The products, 99mTc EDDA2/HYNIC-IAC (P1) and 99mTc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. Results P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 °C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 ± 13.48 vs 51.05 ± 14.05%) when incubated with αvβ3 at a molar excess (0.8 μM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17±0.52 and 2.13±0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 ± 3.67% ID at 4 h whereas 54.04 ± 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by imaging studies showing higher tumor-to-abdominal contrast for P1 than for P2 at 3 h postinjection. Conclusions P1 showed good tumor targeting properties with a rapid tumor uptake, prolonged tumor retention and fast whole-body clearance kinetics. These findings warrant further investigation of the HYNIC method of 99mTc labeling of other peptidomimetic antagonists using EDDA as a coligand. PMID:20556233

Tc-labeling of Peptidomimetic Antagonist to Selectively Target alpha(v)beta(3) Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands.

PubMed

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C P; Wood, Bradford; Carrasquillo, Jorge A; Danthi, S Narasimhan; Paik, Chang H

2010-01-01

OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonist with (99m)Tc for rapid targeting of integrin alpha(v)beta(3) receptors in tumor to produce a high tumor to background ratio. METHODS: The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-beta-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with (99m)Tc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. The products, (99m)Tc EDDA(2)/HYNIC-IAC (P1) and (99m)Tc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. RESULTS: P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 degrees C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 +/- 13.48 vs 51.05 +/- 14.05%) when incubated with alpha(v)beta(3) at a molar excess (0.8 muM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17+/-0.52 and 2.13+/-0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 +/- 3.67% ID at 4 h whereas 54.04 +/- 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by imaging studies showing higher tumor-to-abdominal contrast for P1 than for P2 at 3 h postinjection. CONCLUSIONS: P1 showed good tumor targeting properties with a rapid tumor uptake, prolonged tumor retention and fast whole-body clearance kinetics. These findings warrant further investigation of the HYNIC method of (99m)Tc labeling of other peptidomimetic antagonists using EDDA as a coligand.

Evaluation of a 99mTc-tricine Vascular Disrupting Agent as an In-vivo Imaging in 4T1 Mouse Breast Tumor Model

PubMed Central

Erfani, Mostafa; Shirmardi, Seyed Pezhman; Shafiei, Mohammad

2017-01-01

Colchicine as a vascular disrupting agent creates microtubule destabilization which induces vessel blockage and consequently cell death. Accordingly, colchicines and its analogues radiolabeled with 99mTc may have potential for visualization of tumor. In this work, deacetylcolchicine a colchicine analogue was labeled with 99mTc via tricine as a coligand and characterized for its tumor targeting properties. The in-vitro radiochemical stability and the biodistribution were studied in 4T1 breast tumor model bearing mice. Labeling yield of more than 90% was obtained corresponding to a specific activity of 46 MBq/µmol. In-vivo biodistribution studies demonstrated that radiocomplex had high tumor to muscle and tumor to blood ratios at early time points. Planer gamma imaging of tumor bearing mice showed that this radioconjugate was able to clearly visualize tumors. According to high tumor uptake, presented radiocomplex may have a potential for targeted imaging studies. PMID:29201088

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

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

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

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

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.

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

McAfee, J.G.; Krauss, D.J.; Subramanian, G.

The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less

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.

Radioactive excretion in human milk following administration of /sup 99m/Tc macroaggregated albumin

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

Pittard, W.B.; Merkatz, R.; Fletcher, B.D.

Albumin-tagged sodium pertechnetate (technetium) is routinely used in nuclear medicine for scanning procedures of the lung. The rate of excretion of this radionuclide into breast milk and the resultant potential radiation hazard to the nursing infant have received little attention. Therefore the milk from a nursing mother who required a lung scan because of suspected pulmonary emboli using an intravenous injection of 4 mCi of /sup 99m/Tc macroaggregated human serum albumin was monitored. Albumin tagging severely limited the entrance of technetium into her milk and the radioactivity of the milk returned to base line by 24 hours. A total ofmore » 2.02 muCi of technetium was measured in the 24-hour milk collection after technetium injection and 94% of this amount was excreted by 15.5 hours. This amount of technetium administered orally to a newborn would deliver a total body radiation dose of .3 mrad. Therefore, an infant would receive trivial doses of radiation if breast-feeding were resumed 15.5 hours after administration of the radionuclide to the mother and nursing can clearly be resumed safely 24 hours after injection.« less

Evaluation of the Speed-oligo Direct Mycobacterium tuberculosis Assay for Molecular Detection of Mycobacteria in Clinical Respiratory Specimens

PubMed Central

Lara-Oya, Ana; Mendoza-Lopez, Pablo; Rodriguez-Granger, Javier; Fernández-Sánchez, Ana María; Bermúdez-Ruiz, María Pilar; Toro-Peinado, Inmaculada; Palop-Borrás, Begoña; Navarro-Marí, Jose María

2013-01-01

We present the first evaluation of a novel molecular assay, the Speed-oligo Direct Mycobacterium tuberculosis (SO-DMT) assay, which is based on PCR combined with a dipstick for the detection of mycobacteria and the specific identification of M. tuberculosis complex (MTC) in respiratory specimens. A blind evaluation was carried out in two stages: first, under experimental conditions on convenience samples comprising 20 negative specimens, 44 smear- and culture-positive respiratory specimens, and 11 sputa inoculated with various mycobacterium-related organisms; and second, in the routine workflow of 566 fresh respiratory specimens (4.9% acid-fast bacillus [AFB] smear positives, 7.6% MTC positives, and 1.8% nontuberculous mycobacteria [NTM] culture positives) from two Mycobacterium laboratories. SO-DMT assay showed no reactivity in any of the mycobacterium-free specimens or in those with mycobacterium-related organisms. Compared to culture, the sensitivity in the selected smear-positive specimens was 0.91 (0.92 for MTC and 0.90 for NTM), and there was no molecular detection of NTM in a tuberculosis case or vice versa. With respect to culture and clinical data, the sensitivity, specificity, and positive and negative predictive values for the SO-DMT system in routine specimens were 0.76 (0.93 in smear positives [1.0 for MTC and 0.5 for NTM] and 0.56 in smear negatives [0.68 for MTC and 0.16 for NTM]), 0.99, 0.85 (1.00 in smear positives and 0.68 in smear negatives), and 0.97, respectively. Molecular misidentification of NTM cases occurred when testing 2 gastric aspirates from two children with clinically but not microbiologically confirmed lung tuberculosis. The SO-DMT assay appears to be a fast and easy alternative for detecting mycobacteria and differentiating MTC from NTM in smear-positive respiratory specimens. PMID:23100355

Diagnostic value of (99m)Tc-3PRGD2 scintimammography for differentiation of malignant from benign breast lesions: Comparison of visual and semi-quantitative analysis.

PubMed

Chen, Qianqian; Xie, Qian; Zhao, Min; Chen, Bin; Gao, Shi; Zhang, Haishan; Xing, Hua; Ma, Qingjie

2015-01-01

To compare the diagnostic value of visual and semi-quantitative analysis of technetium-99m-poly-ethylene glycol, 4-arginine-glycine-aspartic acid ((99m)Tc-3PRGD2) scintimammography (SMG) for better differentiation of benign from malignant breast masses, and also investigate the incremental role of semi-quantitative index of SMG. A total of 72 patients with breast lesions were included in the study. Technetium-99m-3PRGD2 SMG was performed with single photon emission computed tomography (SPET) at 60 min after intravenous injection of 749 ± 86MBq of the radiotracer. Images were evaluated by visual interpretation and semi-quantitative indices of tumor to non-tumor (T/N) ratios, which were compared with pathology results. Receiver operating characteristics (ROC) curve analyses were performed to determine the optimal visual grade, to calculate cut-off values of semi-quantitative indices, and to compare visual and semi-quantitative diagnostic values. Among the 72 patients, 89 lesions were confirmed by histopathology after fine needle aspiration biopsy or surgery, 48 malignant and 41 benign lesions. The mean T/N ratio of (99m)Tc-3PRGD2 SMG in malignant lesions was significantly higher than that in benign lesions (P<0.05). When grade 2 of the disease was used as cut-off value for the detection of primary breast cancer, the sensitivity, specificity and accuracy were 81.3%, 70.7%, and 76.4%, respectively. When a T/N ratio of 2.01 was used as cut-off value, the sensitivity, specificity and accuracy were 79.2%, 75.6%, and 77.5%, respectively. According to ROC analysis, the area under the curve for semi-quantitative analysis was higher than that for visual analysis, but the statistical difference was not significant (P=0.372). Compared with visual analysis or semi-quantitative analysis alone, the sensitivity, specificity and accuracy of visual analysis combined with semi-quantitative analysis in diagnosing primary breast cancer were higher, being: 87.5%, 82.9%, and 85.4%, respectively. The area under the curve was 0.891. Results of the present study suggest that the semi-quantitative and visual analysis statistically showed similar results. The semi-quantitative analysis provided incremental value additive to visual analysis of (99m)Tc-3PRGD2 SMG for the detection of breast cancer. It seems from our results that, when the tumor was located in the medial part of the breast, the semi-quantitative analysis gave better diagnostic results.

Kit formulated asialoglycoprotein receptor targeting tracer based on copolymer for liver SPECT imaging.

PubMed

Liu, Chang; Guo, Zhide; Zhang, Pu; Song, Manli; Zhao, Zuoquan; Wu, Xiaowei; Zhang, Xianzhong

2014-08-01

Specific targeting of galactose-carrying molecule to ASGP-R in normal hepatocytes has been demonstrated before. In this study, galactosyl polystyrene was synthesized from controllable ratio of functional monomers and radio-labelled with (99m)Tc by formulated kit for SPECT imaging of hepatic function. p(VLA-co-VNI)(46:54) was synthesized by free-radical copolymerization initiated by AIBN, purified by dialysis, lyophilized to kit with Tricine and TPPTS as co-ligands for (99m)Tc labeling. Radiotracer (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was prepared and evaluated by in vitro stability, in vivo metabolism, ex vivo biodistribution and microSPECT/CT imaging in normal KM mice. MicroSPECT/CT and microMRI imaging were also performed in C57BL/b6 mice with xenograft hepatic carcinoma for hepatic function evaluation. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) was obtained in high radio chemical purity (RCP) (>99%) by using instant kit without further purification and excellent in vitro and in vivo stability. The result of biodistribution showed that liver had high uptake (90.49±10.68 ID%/g) at 30 min after injection and was blocked significantly by cold copolymer. MicroSPECT imaging in normal KM mice at 1h and 4h after injection showed good liver retention and targeting properties. Significant defect of activity was observed in the tumor site which was confirmed by MRI imaging. (99m)Tc-p(VLA-co-VNI)(46:54)(Tricine)(TPPTS) with lower ratio of targeting moiety has no observable effect on the specific binding affinity and liver uptake. This makes it possible to introduce more imaging units for multi-modality imaging. Furthermore, the instant kit preparation of (99m)Tc-labeling provides great potential for the evaluation of hepatocyte function in clinical application. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

PubMed

Jadhav, Swati; Kasaliwal, Rajeev; Shetty, Nitin S; Kulkarni, Suyash; Rathod, Krantikumar; Popat, Bhavesh; Kakade, Harshal; Bukan, Amol; Khare, Shruti; Budyal, Sweta; Jagtap, Varsha S; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

2014-09-01

Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Synthesis and preliminary evaluation of a new (99m)tc labeled substance p analogue as a potential tumor imaging agent.

PubMed

Mozaffari, Saeed; Erfani, Mostafa; Beiki, Davood; Johari Daha, Fariba; Kobarfard, Farzad; Balalaie, Saeed; Fallahi, Babak

2015-01-01

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr(8)-Met(O)(11)-SP] was synthesized and radiolabeled with (99m)Tc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with (99m)Tc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.

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.

Technetium glucose complexes as potential cancer imaging agents.

PubMed

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

2015-10-01

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

Implementation and validation of collapsed cone superposition for radiopharmaceutical dosimetry of photon emitters

NASA Astrophysics Data System (ADS)

Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

2015-10-01

Two collapsed cone (CC) superposition algorithms have been implemented for radiopharmaceutical dosimetry of photon emitters. The straight CC (SCC) superposition method uses a water energy deposition kernel (EDKw) for each electron, positron and photon components, while the primary and scatter CC (PSCC) superposition method uses different EDKw for primary and once-scattered photons. PSCC was implemented only for photons originating from the nucleus, precluding its application to positron emitters. EDKw are linearly scaled by radiological distance, taking into account tissue density heterogeneities. The implementation was tested on 100, 300 and 600 keV mono-energetic photons and 18F, 99mTc, 131I and 177Lu. The kernels were generated using the Monte Carlo codes MCNP and EGSnrc. The validation was performed on 6 phantoms representing interfaces between soft-tissues, lung and bone. The figures of merit were γ (3%, 3 mm) and γ (5%, 5 mm) criterions corresponding to the computation comparison on 80 absorbed doses (AD) points per phantom between Monte Carlo simulations and CC algorithms. PSCC gave better results than SCC for the lowest photon energy (100 keV). For the 3 isotopes computed with PSCC, the percentage of AD points satisfying the γ (5%, 5 mm) criterion was always over 99%. A still good but worse result was found with SCC, since at least 97% of AD-values verified the γ (5%, 5 mm) criterion, except a value of 57% for the 99mTc with the lung/bone interface. The CC superposition method for radiopharmaceutical dosimetry is a good alternative to Monte Carlo simulations while reducing computation complexity.

Implementation and validation of collapsed cone superposition for radiopharmaceutical dosimetry of photon emitters.

PubMed

Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

2015-10-21

Two collapsed cone (CC) superposition algorithms have been implemented for radiopharmaceutical dosimetry of photon emitters. The straight CC (SCC) superposition method uses a water energy deposition kernel (EDKw) for each electron, positron and photon components, while the primary and scatter CC (PSCC) superposition method uses different EDKw for primary and once-scattered photons. PSCC was implemented only for photons originating from the nucleus, precluding its application to positron emitters. EDKw are linearly scaled by radiological distance, taking into account tissue density heterogeneities. The implementation was tested on 100, 300 and 600 keV mono-energetic photons and (18)F, (99m)Tc, (131)I and (177)Lu. The kernels were generated using the Monte Carlo codes MCNP and EGSnrc. The validation was performed on 6 phantoms representing interfaces between soft-tissues, lung and bone. The figures of merit were γ (3%, 3 mm) and γ (5%, 5 mm) criterions corresponding to the computation comparison on 80 absorbed doses (AD) points per phantom between Monte Carlo simulations and CC algorithms. PSCC gave better results than SCC for the lowest photon energy (100 keV). For the 3 isotopes computed with PSCC, the percentage of AD points satisfying the γ (5%, 5 mm) criterion was always over 99%. A still good but worse result was found with SCC, since at least 97% of AD-values verified the γ (5%, 5 mm) criterion, except a value of 57% for the (99m)Tc with the lung/bone interface. The CC superposition method for radiopharmaceutical dosimetry is a good alternative to Monte Carlo simulations while reducing computation complexity.

Investigation of radioactivity concentration in spent technetium generators

NASA Astrophysics Data System (ADS)

Idriss, Hajo; Salih, Isam; Alaamer, Abdulaziz S.; Eisa, M. H.; Sam, A. K.

2014-04-01

This study was carried out to survey and measure radioactivity concentration and estimate radiation dose level at the surface of spent technetium generator columns for the safe final disposal of radioactive waste. High resolution γ-spectrometry with the aid of handheld radiation survey meters has been used. The radioactivity measurements has shown that 238U, 40K and 137Cs were only measurable in one sample whereas 125Sb was found in 14 samples out of total of 20 samples with an activity concentration which ranged from 21 to 7404 with an average value of 1095 Bq/kg. The activity concentration of 125Sb is highly variable indicating that the spent 99mTc generator columns are of different origin. This investigation highlighted the importance of radiation monitoring of spent technetium generators in the country in order to protect workers, and the public from the dangers posed by radioactive waste.

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.

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

Kit for the selective labeling of red blood cells in whole blood with [sup 99]Tc

DOEpatents

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

1992-05-26

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 reduction of technetium. No Drawings

Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

PubMed Central

Pereira, Edgar; do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; Di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

2017-01-01

A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners. PMID:28211920

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

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

Peterfy, C.G.; Rosenthall, L.

1990-12-01

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

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

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.

Preclinical evaluation of (99m)Tc labeled chondroitin sulfate for monitoring of cartilage degeneration in osteoarthritis.

PubMed

Sobal, Grazyna; Velusamy, Kavitha; Kosik, Siegfried; Menzel, Johannes; Hacker, Marcus; Pagitz, Maximilian

2016-06-01

In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs. The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method. In-vivo uptake of (99m)TcCS was evaluated in dogs (n=12, castrated males, 4-9years, with 15-51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only. In healthy control dogs we did not detect any specific uptake of (99m)TcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented. Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls. In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I-III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of (99m)TcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects. These results suggest that (99m)TcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Method of tagging excipients with /sup 99m/Tc

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

Bardy, A.; Beydon, J.; Gobin, R.

1977-11-08

A method of using /sup 99m/technetium for tagging excipients in medical diagnosis by scintigraphy comprises mixing, in an aqueous solution of alkali-metal pertechnetate, an excipient and a reducing agent in the form of a complex, which complex is such that the association constant of the anion with reduced techetium is less than the association constant of the excipient with reduced technetium, thereby forming a radio-pharmaceutical substance which is a complex between the excipient and /sup 99m/technetium.

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. Log P analysis of the (99m)Tc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a') compared to the peptide with the unmodified DPA chelate (9a'). In vivo biodistribution analysis of 9a' and 10a' showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a' compared to predominantly hepatic accumulation for 9a'. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[M(I)(CO)3](+) complexes in future studies.

Differences in the intracellular processing of the radiolabel following the uptake of iodine-125- and technetium-99m-neogalactosyl albumin by the isolated perfused rat liver

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

Gore, S.; Morris, A.I.; Gilmore, I.T.

1991-03-01

Neogalactosyl albumin (NGA) is a synthetic ligand to the asialoglycoprotein receptor (hepatic binding protein), which has been proposed as a useful receptor binding radiopharmaceutical for the noninvasive assessment of liver function. We have compared the uptake and intracellular processing of iodine-125- (125I) and technetium-99m- ({sup 99m}Tc) NGA following its administration as a 1-min pulse (147 pmol) to the isolated perfused rat liver. Approximately 40% of a pulse of either {sup 125}I- or {sup 99m}Tc-NGA were taken up first pass by the liver. Of the {sup 125}I taken up by the liver, 82% was released after 15-20 min at the sinusoidalmore » pole of the hepatocyte, predominantly as small molecular weight metabolites. A further 8% of the {sup 125}I-associated radioactivity was secreted as intact NGA into bile by the non-lysosomal (direct) pathway while 6% remained in the liver 1 hr after the pulse. In contrast, of the {sup 99m}Tc taken up by the liver, only 4% reappeared in the perfusate while 40% was secreted into bile by the lysosomal (indirect) pathway and 55% remained in the liver 1 hr after the pulse. Since labeled metabolites of {sup 99m}Tc-NGA do not appear in plasma, this permits kinetic modeling with {sup 99m}Tc-NGA without correction for labeled metabolites. Thus, {sup 99m}Tc-NGA is an excellent candidate as a receptor-binding radiopharmaceutical.« less

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors

PubMed Central

Barollo, Susi; Bertazza, Loris; Watutantrige-Fernando, Sara; Censi, Simona; Cavedon, Elisabetta; Galuppini, Francesca; Pennelli, Gianmaria; Fassina, Ambrogio; Citton, Marilisa; Rubin, Beatrice; Pezzani, Raffaele; Benna, Clara; Opocher, Giuseppe; Iacobone, Maurizio; Mian, Caterina

2016-01-01

Background 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC. Methods Real-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization. Results LAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization. Conclusions The present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells. PMID:27224648

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy. PMID:23618132

Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): in vitro and in vivo studies.

PubMed

Kim, Eun-Mi; Jeong, Hwan-Jeong; Park, In-Kyu; Cho, Chong-Su; Moon, Hyung-Bae; Yu, Dae-Yeul; Bom, Hee-Seung; Sohn, Myung-Hee; Oh, In-Joon

2005-11-28

The asialoglycoprotein receptor (ASGP-R) on the hepatocyte membrane is a specific targeting marker for gene and drug delivery. Polyethylenimine (PEI) is a polycationic nonviral vector that is used for gene transfer. We have synthesized galactosylated polyethylenimine-graft-poly(ethylene glycol) (GPP) for performing gene delivery to the hepatocytes. The present study reports on the in vitro and in vivo data that was achieved in hepatoma bearing transgenic mice. The cytotoxicity was decreased with the increasing PEG content. The particle size of the complex was increased with the increasing PEG at an N/P ratio of 3.0, while the zeta potentials were decreased. The (99m)Tc labeled complexes were transfected into HepG2 and HeLa cells, while the GFP reporter genes were mainly expressed in the HepG2 cells. The in vivo data was achieved in ALB/c-Ha-ras transgenic mice. (99m)Tc labeled GPP(50)/DNA was injected into the mice via the tail vein, and the gamma images were acquired at 5, 15 and 30 min. The (99m)Tc labeled complexes were mainly localized in the heart and liver, and they were excreted through the kidneys. The GFP gene was mainly expressed in the proliferating cells at the tumor periphery. This result was confirmed by PCNA staining. The GPP(50)/DNA complexes were bound to ASGP-R of the proliferating hepatocytes in vitro and in vivo. The present results demonstrate the feasibility of nonviral gene transfer using galactosylated PEI-PEG in vivo.

Scintigraphic diagnosis of gastric carcinoma (in Hebrew)

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

Czerniak, D.

1972-09-01

During the past 10 years efforts have been made to develop a radioisotope test for gastric malignancy. Phosphorus-32 was used by intracavity procedures (gastric tube-detector; autoradiography) but the procedures were difficult. In 1961 the first scintillographic assays with scanners and then with scintillation cameras were performed. Iodine-131 was used at first and since 1965 /sup 99m/Tc, which is superior from a physical point of view. It was established that a cold space-occupying lesion in the gastroscan indicates malignancy and that a foggy scan, general or local, may also indicate a neoplastic lesion. All other conditions, including peptic ulcer and gastritis,more » give a normal scan. In the dog, injection of /sup 99m/Tc indicated a turnover of the isotope in the body, and that it is concentrated in the gastric mucosa and excreted in the gastric juice. A gastroscintillographic study in 220 patients showed that 54 of them had stomach malignancies (51 carcinoma and 3 sarcoma). Only neoplasms at least 2 cm in diameter were visualized. In all the patients, clinical, radiological, and biochemical examinations were performed and in most, pathological examinations as well. There was correspondence with the final diagnosis in 80% of the scintillographed cancers and in 92% of those studied roentgenologically. The false scinttllographic diagnosed conclusions were mostly in diffurent patients than in those with false roentgenological diagnoses. It can therefore be concluded that the two methods are complementary. The radiological exposure due to /sup 99m/Tc scintivisualization is low, 200 mrad to the stomach and l5 mrad to the whole body. (INIS)« less

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

Jones, D.K.; Higenbottam, T.W.

Despite no radiographic change, a patient with Pneumocystis pneumonia showed increased clearance of inhaled /sup 99m/Tc DTPA from lung to blood. Gas transfer for carbon monoxide was also reduced, but improved with treatment. This was paralleled by serial increase in the t1/2 LB.

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.

Contraction dynamics and function of the muscle-tendon complex depend on the muscle fibre-tendon length ratio: a simulation study.

PubMed

Mörl, Falk; Siebert, Tobias; Häufle, Daniel

2016-02-01

Experimental studies show different muscle-tendon complex (MTC) functions (e.g. motor or spring) depending on the muscle fibre-tendon length ratio. Comparing different MTC of different animals examined experimentally, the extracted MTC functions are biased by, for example, MTC-specific pennation angle and fibre-type distribution or divergent experimental protocols (e.g. influence of temperature or stimulation on MTC force). Thus, a thorough understanding of variation of these inner muscle fibre-tendon length ratios on MTC function is difficult. In this study, we used a hill-type muscle model to simulate MTC. The model consists of a contractile element (CE) simulating muscle fibres, a serial element (SE) as a model for tendon, and a parallel elastic element (PEE) modelling tissue in parallel to the muscle fibres. The simulation examines the impact of length variations of these components on contraction dynamics and MTC function. Ensuring a constant overall length of the MTC by L(MTC) = L(SE) + L(CE), the SE rest length was varied over a broad physiological range from 0.1 to 0.9 MTC length. Five different MTC functions were investigated by simulating typical physiological experiments: the stabilising function with isometric contractions, the motor function with contractions against a weight, the capability of acceleration with contractions against a small inertial mass, the braking function by decelerating a mass, and the spring function with stretch-shortening cycles. The ratio of SE and CE mainly determines the MTC function. MTC with comparably short tendon generates high force and maximal shortening velocity and is able to produce maximal work and power. MTC with long tendon is suitable to store and release a maximum amount of energy. Variation of muscle fibre-tendon ratio yielded two peaks for MTC's force response for short and long SE lengths. Further, maximum work storage capacity of the SE is at long relL(SE,0). Impact of fibre-tendon length ratio on MTC functions will be discussed. Considering a constant set of MTC parameters, quantitative changes in MTC performance (work, stiffness, force, energy storage, dissipation) depending on varying muscle fibre-tendon length ratio were provided, which enables classification and grading of different MTC designs.

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.

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.

The 'Lumbar Fusion Outcome Score' (LUFOS): a new practical and surgically oriented grading system for preoperative prediction of surgical outcomes after lumbar spinal fusion in patients with degenerative disc disease and refractory chronic axial low back pain.

PubMed

Mattei, Tobias A; Rehman, Azeem A; Teles, Alisson R; Aldag, Jean C; Dinh, Dzung H; McCall, Todd D

2017-01-01

In order to evaluate the predictive effect of non-invasive preoperative imaging methods on surgical outcomes of lumbar fusion for patients with degenerative disc disease (DDD) and refractory chronic axial low back pain (LBP), the authors conducted a retrospective review of 45 patients with DDD and refractory LBP submitted to anterior lumbar interbody fusion (ALIF) at a single center from 2007 to 2010. Surgical outcomes - as measured by Visual Analog Scale (VAS/back pain) and Oswestry Disability Index (ODI) - were evaluated pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year post-operatively. Linear mixed-effects models were generated in order to identify possible preoperative imaging characteristics (including bone scan/99mTc scintigraphy increased endplate uptake, Modic endplate changes, and disc degeneration graded according to Pfirrmann classification) which may be predictive of long-term surgical outcomes . After controlling for confounders, a combined score, the Lumbar Fusion Outcome Score (LUFOS), was developed. The LUFOS grading system was able to stratify patients in two general groups (Non-surgical: LUFOS 0 and 1; Surgical: LUFOS 2 and 3) that presented significantly different surgical outcomes in terms of estimated marginal means of VAS/back pain (p = 0.001) and ODI (p = 0.006) beginning at 3 months and continuing up to 1 year of follow-up. In conclusion,  LUFOS has been devised as a new practical and surgically oriented grading system based on simple key parameters from non-invasive preoperative imaging exams (magnetic resonance imaging/MRI and bone scan/99mTc scintigraphy) which has been shown to be highly predictive of surgical outcomes of patients undergoing lumbar fusion for treatment for refractory chronic axial LBP.

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 basic conditions. The results of this fundamental study offer protocols and guidance useful for the design and preparation of fac-[(99m)Tc(I)(CO)(3)L](n) agents consisting of a single tracer.

Substitution of the Lys Linker with the β-Ala Linker Dramatically Decreased the Renal Uptake of 99mTc-Labeled Arg-X-Asp-Conjugated and X-Ala-Asp-Conjugated α-Melanocyte Stimulating Hormone Peptides

PubMed Central

2015-01-01

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg11)CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg11)CCMSH (2), RVD-β-Ala-(Arg11)CCMSH (3), RAD-β-Ala-(Arg11)CCMSH (4), NAD-β-Ala-(Arg11)CCMSH (5), and EAD-β-Ala-(Arg11)CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their 99mTc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six 99mTc-peptides. 99mTc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these 99mTc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 99mTc-4 as an imaging probe. PMID:25290883

Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

PubMed

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

2014-11-13

The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

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.

Identification of Staphylococcus aureus infection by aptamers directly radiolabeled with technetium-99m.

PubMed

dos Santos, Sara Roberta; Rodrigues Corrêa, Cristiane; Branco de Barros, André Luís; Serakides, Rogéria; Fernandes, Simone Odília; Cardoso, Valbert Nascimento; de Andrade, Antero Silva Ribeiro

2015-03-01

Aptamers are oligonucleotides that have high affinity and specificity for their molecular targets which are emerging as a new class of molecules for radiopharmaceuticals development. In this study, aptamers selected to Staphylococcus aureus were evaluated for bacterial infection identification. Anti S. aureus aptamers were labeled with (99m)Tc by the direct method. The radiolabel yield and complex stability were assessed by thin-layer chromatography (TLC). Three groups of Swiss mice containing 6 animals each were used. The first group was infected intramuscularly in the right thigh with S. aureus. The second group was infected in the same way with C. albicans and the third group was injected with zymosan to induce aseptic inflammation. After 24 h, radiolabeled aptamers (22.2 MBq) were injected by the tail vein. The mice were euthanized 4 h post injection and tissue sample activities measured in a gamma counter. The (99m)Tc labeled aptamers were stable in saline, plasma and cystein excess. Radiolabeled aptamers showed increased uptake in the kidneys for all groups indicating a main renal excretion, which is consistent with the hydrophilic nature and small size of aptamers. The radiopharmaceutical showed rapid blood clearance indicated by a reduced dose (% ID/g) in the blood. The biodistribution showed that aptamers were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 4.0±0.5. This ratio for mice infected with C. albicans was 2.0±0.4 while for mice with aseptic inflammation was 1.2±0.2. Histology confirmed the presence of infection in groups 1 and 2, and inflammation in group 3. The biodistibution study demonstrated a statistically higher uptake in the S. aureus foci relative to inflammation and C. albicans infected areas. These results highlight the potential of aptamers labeled directly with (99m)Tc for bacterial infection diagnosis by scintigraphy. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluating abdominal oedema during experimental sepsis using an isotope technique.

PubMed

Lattuada, Marco; Maripuu, Enn; Segerstad, Carl Hard af; Lundqvist, Hans; Hedenstierna, Göran

2012-05-01

Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients. We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed ('septic') piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium-99m ((99m)Tc) and Transferrin labelled with Indium111 ((111)In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique. No (99m)Tc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, (111)In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4·06 times higher in the LPS group compared to the healthy controls (P<0·0001). Abdominal free fluid, studied in 3 animals, had as high (111)In activity as in plasma, but no (99m)Tc activity. Intestinal lymphatic vessel size was higher in LPS (3·7 ± 1·1 μm) compared to control animals (0·6 + 0·2 μm; P<0·001) and oedema correlated to villus diameter (R(2) = 0·918) and lymphatic diameter (R(2) = 0·758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0·46*IAP-3·3 (R(2) = 0·56). The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Synthesis and Preliminary Evaluation of a New 99mTc Labeled Substance P Analogue as a Potential Tumor Imaging Agent

PubMed Central

Mozaffari, Saeed; Erfani, Mostafa; Beiki, Davood; Johari Daha, Fariba; Kobarfard, Farzad; Balalaie, Saeed; Fallahi, Babak

2015-01-01

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr8-Met(O)11-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with 99mTc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors. PMID:25561916

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism.

PubMed

Ko, Toshiyuki; Utanohara, Yuko; Suzuki, Yasuhiro; Kurihara, Makiko; Iguchi, Nobuo; Umemura, Jun; Sumiyoshi, Tetsuya; Tomoike, Hitonobu

2016-01-01

Simultaneous dual-isotope SPECT imaging with 201Tl and (123)I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion-metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, (99m)Tc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of (99m)Tc and (123)I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between (99m)Tc and (123)I. In the subsequent clinical study, (99m)Tc-MIBI/(123)I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by (99m)Tc-MIBI and (123)I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional (201)TlCl/(123)I-BMIPP dual-isotope imaging, the use of (99m)Tc-MIBI instead of (201)TlCl improves image quality as well as lowers radiation exposure.

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.

Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

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

Rajagopalan, Raghavan

The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling studymore » revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.« less

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

PubMed

Oda, Kenji; Matsushima, Eisuke; Okubo, Yoshiro; Ohta, Katsuya; Murata, Yuji; Koike, Ryuji; Miyasaka, Nobuyuki; Kato, Motoichiro

2005-07-01

Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging

NASA Astrophysics Data System (ADS)

Singh, Sweta; Tiwari, Anjani K.; Varshney, Raunak; Mathur, R.; Shukla, Gauri; Bag, N.; Singh, B.; Mishra, Anil K.

2016-01-01

2,2‧,2″-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11-tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N-methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2-ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized and evaluated for imaging application. The pharmacokinetics of these ligands were determined by tracer methods. In vitro human serum stability of 99mTc Met-ac-TE3A/99mTc Bis(thiosemicarbazone)-Biotin after 24 h was found to be 96.5% and 97.0% respectively. Blood kinetics of both ligands in normal rabbits showed biphasic clearance pattern. Ex vivo biodistribution study revealed significant initial tumor uptake and high tumor/muscles ratio which is a pre-requisite condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging.

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

1997-02-11

A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

[Nuclear cardiology with new radiopharmaceuticals].

PubMed

Bunko, H

1994-08-01

In the field of nuclear cardiology, 99mTc labeled myocardial perfusion agents such as MIBI, Tetrofosmin and Teboroxime, 111In-antimyosin for imaging of myocardial necrosis, 123I-betamethyl-iodophenylpentadecanoic acid (BMIPP) for imaging of myocardial fatty acid metabolism and 123I-metaiodobenzylguanidine (MIBG) for imaging of myocardial adrenergic function are introduced recently in Japan. Improved image quality and simultaneous evaluation of myocardial perfusion, function and wall motion can be obtained with use of 99mTc labeled myocardial perfusion agents. 111In-antimyosin enables specific imaging of myocardial necrosis which leads to the use for wide variety of heart diseases. Discrepancy of the myocardial perfusion and metabolism in case of stunned myocardium or cardiomyopathy can be evaluated by 123I-BMIPP in conjunction with perfusion agent. Recently wide variety of diseases which may have cardiac adrenergic abnormality are targeted for 123I-MIBG imaging. These new radiopharmaceuticals are expected to be powerful tool for evaluation of the pathophysiology including severity and prognosis and evaluation of the etiology of the various heart diseases.

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 interest was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate the (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 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 dose estimates. In three breast cancer patients with histologically confirmed cancer, static images were obtained at 1 h in the supine position with hands placed behind the head. (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained from lyophilized kits demonstrated high stability in human serum and specific cell receptor binding. The biodistribution data from mice showed rapid blood clearance, with both renal and hepatobiliary excretion, and specific binding towards α(ν)β(3) integrins in the MCF7 tumours. In women, the blood activity showed a half-life value of 1.60 min for the fast component (T1/2α = ln2/26.01) and half-life values of 1.0 h for the first slow component (T1/2β = ln2/0.69) and 4.03 h for the second slow component (T1/2γ = ln2/0.16). Images from patients showed an average tumour/heart (blood) ratio of 3.61 ± 0.62 at 1 h. The average equivalent doses calculated for a study using 740 MBq were 4.9, 6.2, 20.7, 34.5 and 57.0 mSv for the liver, intestines, spleen, kidneys and thyroid, respectively, and the effective dose was 6.1 mSv. All absorbed doses were comparable to those known from most of the (99m)Tc studies. (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained from kit formulations showed high tumour uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical for targeting site-specific breast cancer. The results obtained in this study warrant further clinical studies to determine the specificity and sensitivity of (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2.

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.

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.

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).

Sodium 18F-Fluoride PET/CT of Bone, Joint and Other Disorders

PubMed Central

Jadvar, Hossein; Desai, Bhushan; Conti, Peter S.

2014-01-01

The use of 18F-sodium fluoride (18F-NaF) with positron emission tomography-computed tomography (PET/CT) is increasing. This resurgence of an old tracer has been fueled by several factors including superior diagnostic performance over standard 99mTc-based bone scintigraphy, growth in the availability of PET/CT imaging systems, increase in the number of regional commercial distribution centers for PET radiotracers, the recent concerns about potential chronic shortages with 99mTc based radiotracers, and the recent decision by the Centers for Medicare and Medicaid Services to reimburse for 18F-NaF PET/CT for evaluation of patients with known or suspected bone metastases through the National Oncologic PET Registry. The major goal of this article is to review the current evidence on the diagnostic utility of 18F-NaF in the imaging assessment of bone and joint in a variety of clinical conditions. PMID:25475379

In vivo and in vitro characterization of CCK8 bearing a histidine-based chelator labeled with 99mTc-tricarbonyl.

PubMed

D'Andrea, Luca D; Testa, Irma; Panico, Mariarosaria; Di Stasi, Rossella; Caracò, Corradina; Tarallo, Laura; Arra, Claudio; Barbieri, Antonio; Romanelli, Alessandra; Aloj, Luigi

2008-01-01

The development of receptor targeting radiolabeled ligands has gained much interest in recent years for diagnostic and therapeutic applications in nuclear medicine. Cholecystokinin (CCK) receptors have been shown to be overexpressed in a subset of neuroendocrine and other tumors. We are evaluating binding and biodistribution properties of a CCK8 peptide derivative labeled with (99m)Tc(I)-tricarbonyl. The CCK8 peptide was modified at its N-terminus by adding to its N-terminus two lysine-histidine modules (KH), where histidine is coupled to the side chain of the lysine ((KH)(2)-CCK8). (99m)Tc(I)-tricarbonyl was generated with the IsoLinktrade mark kit. A431 cells stably transfected with a cDNA encoding for the human CCK2 receptor were utilized to determine binding affinity, internalization, and retention of the labeled peptide, in comparison with wild-type A431 cells. A nude mouse tumor model was obtained by generating A431-CCK2R and A431-control tumors in opposite flanks of the animals. High specific activity labeling with (99m)Tc was achieved. In A431-CCK2R cells, specific saturable binding was observed as well as evident internalization of the radiolabeled peptide after binding. Biodistribution experiments showed rapid, specific localization of (KH)(2)-CCK8 on A431-CCK2R xenografts compared with control tumors, although absolute uptake values were not markedly higher compared with background activity. Clearance of unbound radioactivity was both urinary and hepatobiliary. In imaging experiments, while targeting to CCK2R positive tumors could be appreciated, there was poor contrast between target and nontarget areas. (KH)(2)-CCK8 shows adequate in vitro and in vivo properties for CCK2R targeting although improvement of biodistribution warrant further development. (c) 2008 Wiley Periodicals, Inc.

Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications.

PubMed

Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A

2012-07-01

Electrochemical separation techniques are not widely used in radionuclide generator technology and only a few studies have been reported [1-4]. Nevertheless, this strategy is useful when other parent-daughter separation techniques are not effective or not possible. Such situations are frequent when low specific activity (LSA) parent radionuclides are used for instance with adsorption chromatographic separations, which can result in lower concentration of the daughter radionuclide in the eluent. In addition, radiation instability of the column matrix in many cases can affect the performance of the generator when long lived parent radionuclides are used. Intricate knowledge of the chemistry involved in the electrochemical separation is crucial to develop a reproducible technology that ensures that the pure daughter radionuclide can be obtained in a reasonable time of operation. Crucial parameters to be critically optimized include the applied potential, choice of electrolyte, selection of electrodes, temperature of electrolyte bath and the time of electrolysis in order to ensure that the daughter radionuclide can be reproducibly recovered in high yields and high purity. The successful electrochemical generator technologies which have been developed and are discussed in this paper include the (90)Sr/(90)Y, (188)W/(188)Re and (99)Mo/(99m)Tc generators. Electrochemical separation not only acts as a separation technique but also is an effective concentration methodology which yields high radioactive concentrations of the daughter products. The lower consumption of reagents and minimal generation of radioactive wastes using such electrochemical techniques are compatible with 'green chemistry' principles.

[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.

Pre-clinical and Clinical Evaluation of High Resolution, Mobile Gamma Camera and Positron Imaging Devices

DTIC Science & Technology

2009-10-01

Field-of-View, Mobile PET/SPECT System for Bedside Environments: A Dynamic Cardiac Phantom Study using 99mTc and 18F- FDG . Presented at the American...using Tc-99m tracers and viability imaging using F- 18 tracers [3]-[7]. For cardiac F-18 imaging in a bedside environment, the 511 keV SPECT approach...SPECT system may have difficulty imaging subtle myocardial defects with F-18 tracers , but it may effectively image moderate to severe defects. The

Technetium 99m pertechnetate scans in congenital hypothyroidism

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

Bauman, R.A.; Bode, H.H.; Hayek, A.

1976-08-01

Goiters are rarely palpable in infants with congenital hypothyroidism except in the case of maternal ingestion of iodide. The presence or absence of glandular tissue is, however, important for genetic and prognostic counseling and for acceleration of diagnosis in other affected siblings. The detection of thyroid tissue by /sup 99m/Tc pertechnetate scans in a significant number of our patients heretofore considered athyreotic establishes that physical findings and traditional laboratory data are not adequate to determine whether or not thyroid tissue is present.

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

Yu, S; Green, G; Sehgal, V

Purpose: The purpose of this study is to assess the dose response of radioembolization using yttrium-90 (Y-90) microspheres in patients treated for unresectable cholangiocarcinoma. This study utilized partition dosimetry model for the dose calculation. The results show survival benefit with dose escalation. Methods: Between February 2009 and March 2013, ten patients with pathology proven unresectable cholangiocarcinoma were radioembolized with Y-90 microspheres. Patients underwent initial pre-treatment angiographic assessment for blood flow and 99mTc- MAA for lung shunt evaluation. Activity of Y-90 administration was calculated using the Body Surface Area (BSA) and target volumes which were determined by contouring the pre-treatment MRI/CTmore » images using a radiation therapy treatment planning system. Medical Internal Radiation Dose (MIRD) method was used to assess the dosimetric results of Y90. Partition model based on the tumor to-liver activity uptake estimated from pretreatment 99mTc- MAA study was used to calculate the dose delivered to the target. The variables assessed included: administered dose, toxicity based on clinical changes, imaging based tumor response, and survival. Results: Ten patients were radioembolized with Y-90 microspheres to either one hepatic lobe or both left and right lobes. Patients were stratified by dose. Four patients who received dose greater than 140Gy (p < 0.05) all survived. The corresponding activity they received was greater than 35 mCi. Six out of ten patients died of disease with median survival of 18 weeks (range 12–81wks). Conclusion: Given the growing body of data for Y-90 microspheres in the context of cholangiocarcinoma, radioembolization may become an important treatment modality for an appropriately selected group of patients. Our study further substantiates past studies and shows additional evidence of a survival benefit with dose escalation.« less

Evaluation of a measurement system for Uranium electrodeposition control to radiopharmaceuticals production

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

Tufic Madi Filho; Adonis Marcelo Saliba Silva; Jose Patricio Nahuel Cardenas

2015-07-01

For 2016, studies by international bodies forecast a crisis in the supply of Molybdenum ({sup 99}Mo), which is the generator of {sup 99m}Tc, widely used for medical diagnoses and treatments. As a result, many countries are making efforts to prevent this crisis. Brazil is developing the Brazilian Multipurpose Reactor (RMB) project, under the responsibility of the National Nuclear Energy Commission (CNEN). The RMB is a nuclear reactor for research and production of radioisotopes used in the production of radiopharmaceuticals and radioactive sources, broadly used in industrial and research areas in Brazil. Electrodeposition of uranium is a common practice to createmore » samples for alpha spectrometry and this methodology may be an alternative way to produce targets of low enriched uranium (LEU) to fabricate radiopharmaceuticals, as {sup 99}Mo, used for cancer diagnosis. To study the electrodeposition, a solution of 10 mM uranyl nitrate, in 2-propanol, containing uranium enriched to 2.4% in {sup 235}U, with pH = 1, was prepared and measurements with an alpha spectrometer were performed. These studies are justified by the need to produce {sup 99}Mo since, despite using molybdenum in bulk, Brazil is totally dependent on its import. In this project, we intend to obtain a process that may be technologically feasible to control the radiation targets for {sup 99}Mo production. (authors)« less

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome

PubMed Central

Zhang, Guangjian; Gao, Rui; Wang, Yuanbo; Liu, Yan; Li, Juan; Jia, Xi; Liang, Yiqian; Yang, Aimin

2018-01-01

Aims To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake. PMID:29423055

In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate

PubMed Central

Garcia-Pinto, Angélica B.; Santos-Filho, Sebastião D.; Carvalho, Jorge J.; Pereira, Mário J. S.; Fonseca, Adenilson S.; Bernardo-Filho, Mário

2013-01-01

Background: Natural products might alter the labeling of blood constituents with technetium-99m (99mTc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. Objective: This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). Materials and Methods: To study the effect of the CE on the labeling of blood constituents with 99mTc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na99mTcO4) in Wistar rats, these animals were treated or not with a CE. Na99mTcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. Result: In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na99mTcO4 was observed in stomach after in vivo treatment. Conclusion: These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences. PMID:24143045

Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

PubMed

Okur, Neslihan Üstündağ; Özdemir, Derya İlem; Kahyaoğlu, Şennur Görgülü; Şenyiğit, Zeynep Ay; Aşıkoğlu, Makbule; Genç, Lütfi; Karasulu, H Yeşim

2015-01-01

The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.

Production of Medical Isotopes with Electron Linacs

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

Rotsch, D A; Alford, K.; Bailey, J. L.

Radioisotopes play important roles in numerous areas ranging from medical treatments to national security and basic research. Radionuclide production technology for medical applications has been pursued since the early 1900s both commercially and in nuclear science centers. Many medical isotopes are now in routine production and are used in day-to-day medical procedures. Despite these advancements, research is accelerating around the world to improve the existing production methodologies as well as to develop novel radionuclides for new medical appli-cations. Electron linear accelerators (linacs) represent a unique method for the production of radioisotopes. Even though the basic technology has been around formore » decades, only recently have electron linacs capable of producing photons with sufficient energy and flux for radioisotope production become available. Housed in Argonne Nation-al Laboratory’s Low Energy Accelerator Facility (LEAF) is a newly upgraded 55 MeV/25-kW electron linear ac-celerator, capable of producing a wide range of radioiso-topes. This talk will focus on the work being performed for the production of the medical isotopes 99Mo (99Mo/99mTc generator), 67Cu, and 47Sc.« less

Adsorption of (99m)Tc-radiopharmaceuticals onto injection vials and syringes.

PubMed

Mushtaq, Ahmad; Ur Rehman, Taj; Safdar Mansur, Muhammad; Jehangir, Mustanser

2008-06-01

Many groups have reported the adsorption or retention of (99m)Tc-radiopharmaceuticals on injection vials and disposable plastic syringes. Such an enormously high loss of radioactivity would result in poor images, radiation exposure, waste, and economic burdens. We therefore decided to investigate the extent of adsorption or retention of several (99m)Tc-radiopharmaceuticals on injection vials, rubber stoppers, and plastic syringes. These radiopharmaceuticals are produced as lyophilized kits in our department and supplied to various hospitals practicing nuclear medicine in Pakistan. A vial containing lyophilized material was reconstituted with 3 mL of freshly eluted Na(99m)TcO(4). A 1-mL aliquot of the resulting solution was withdrawn into a syringe at 0.25, 0.5, 1, 3, and 5 h after preparation. All preparations were stored at room temperature ( approximately 22 degrees C). After each withdrawal, the vial was reweighed and the activity remaining in the vial was measured using a radioisotope calibrator. The sample was reinjected into the vial. From the original weight and activity of solution in the vial, the initial activity per gram was calculated. From the weight and activity remaining in the vial after withdrawal of the sample, the activity per gram of the sample was calculated. From the difference between the initial activity per gram and the activity per gram of the sample, the percentage of (99m)Tc adsorbed on the vial was calculated. All preparations were kept in the syringe for 15 min, and the activity was measured before and after the syringe was emptied. The needle and plunger of the syringe were separated, and activity in the needle and plunger was also measured. The labeling efficiency of all radiopharmaceuticals used during these studies was more than 95%. In most cases, the activity of (99m)Tc found on the rubber stopper was less than 1%. Adsorption of (99m)Tc onto vials increased gradually with storage time. Adsorption was minimal at the initial stages, whereas maximum retention was noted after 5 h. Nearly 5% adsorption of activity was observed after 5 h of storage time on vials of sestamibi, mercaptoacetyltriglycine, dextran, ciprofloxacin, and dimercaptosuccinic acid (III and V). Retention of activity on needles ranged from 1% to 2% for all preparations studied. Plungers did not show any significant retention of radioactivity; in most cases, retention was less than 0.5%. The maximum retention of radioactivity on plastic syringe bodies was more than 3% for sestamibi, dimercaptosuccinic acid, dextran, pyrophosphate, and phytate. The results revealed that losses of radioactivity from (99m)Tc-radiopharmaceuticals in these objects (glass vial, rubber stopper, plastic syringes, plungers, and needles) are not alarming in our setup.

Scatter and cross-talk correction for one-day acquisition of 123I-BMIPP and 99mtc-tetrofosmin myocardial SPECT.

PubMed

Kaneta, Tomohiro; Kurihara, Hideyuki; Hakamatsuka, Takashi; Ito, Hiroshi; Maruoka, Shin; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo

2004-12-01

123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TET) are widely used for evaluation of myocardial fatty acid metabolism and perfusion, respectively. ECG-gated TET SPECT is also used for evaluation of myocardial wall motion. These tests are often performed on the same day to minimize both the time required and inconvenience to patients and medical staff. However, as 123I and 99mTc have similar emission energies (159 keV and 140 keV, respectively), it is necessary to consider not only scattered photons, but also primary photons of each radionuclide detected in the wrong window (cross-talk). In this study, we developed and evaluated the effectiveness of a new scatter and cross-talk correction imaging protocol. Fourteen patients with ischemic heart disease or heart failure (8 men and 6 women with a mean age of 69.4 yr, ranging from 45 to 94 yr) were enrolled in this study. In the routine one-day acquisition protocol, BMIPP SPECT was performed in the morning, with TET SPECT performed 4 h later. An additional SPECT was performed just before injection of TET with the energy window for 99mTc. These data correspond to the scatter and cross-talk factor of the next TET SPECT. The correction was performed by subtraction of the scatter and cross-talk factor from TET SPECT. Data are presented as means +/- S.E. Statistical analyses were performed using Wilcoxon's matched-pairs signed-ranks test, and p < 0.05 was considered significant. The percentage of scatter and cross-talk relative to the corrected total count was 26.0 +/- 5.3%. EDV and ESV after correction were significantly greater than those before correction (p = 0.019 and 0.016, respectively). After correction, EF was smaller than that before correction, but the difference was not significant. Perfusion scores (17 segments per heart) were significantly lower after as compared with those before correction (p < 0.001). Scatter and cross-talk correction revealed significant differences in EDV, ESV, and perfusion scores. These observations indicate that scatter and cross-talk correction is required for one-day acquisition of 123I-BMIPP and 99mTc-tetrofosmin SPECT.

Generalized five-dimensional dynamic and spectral factor analysis

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

El Fakhri, Georges; Sitek, Arkadiusz; Zimmerman, Robert E.

2006-04-15

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming thatmore » primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where {sup 99m}Tc and {sup 123}I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary {sup 99m}Tc (bias=6.4%{+-}4.3%) and {sup 123}I (-1.7%{+-}6.9%) time activity curves (TAC) compared to conventional FADS (biases=15.5%{+-}10.6% in {sup 99m}Tc and 8.3%{+-}12.7% in {sup 123}I, p<0.05). Our technique was also validated in two primate dynamic dual isotope perfusion/DAT transporter studies. Biases of {sup 99m}Tc-HMPAO and {sup 123}I-DAT activity estimates with respect to estimates obtained in the presence of only one radionuclide (sequential imaging) were significantly lower with 5D-GFA (9.4%{+-}4.3% for {sup 99m}Tc-HMPAO and 8.7%{+-}4.1% for {sup 123}I-DAT) compared to biases greater than 15% for volumes of interest (VOI) over the reconstructed volumes (p<0.05). 5D-GFA is a novel and promising approach in dynamic SPECT imaging that can also be used in other modalities. It allows accurate and precise dynamic analysis while compensating for Compton scatter and cross-talk.« less

Radioisotope imaging for the evaluation of thyroid neoplasia and hypothyroidism in a dog

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

Branam, J.E.; Leighton, R.L.; Hornof, W.J.

1982-05-01

An 11-year-old dog was diagnosed as having concurrent unilateral follicular thyroid carcinoma and hypothyroidism. Radioisotope imaging with /SUP 99m/Tc as sodium pertechnatate identified the extent of thyroid tissue involvement. A combination of surgical resection and hormonal supplementation resulted in a favorable clinical response.

Partial growth plate closure: apex view on bone scan

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

Howman-Giles, R.; Trochei, M.; Yeates, K.

1985-01-01

A new technique of using /sup 99m/Tc bone scan to assess partial closure of the growth plate is described. The site and degree of osseous fusion can be obtained by using the apex view. The technique has the potential of assessing serially the growth of a plate before and after surgery.

Bone scan findings in hypervitaminosis D: case report. [/sup 99m/Tc tracer technique

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

Fogelman, I.; McKillop, J.H.; Cowden, E.A.

1977-12-01

Bone scans in three patients showed generalized symmetrical increased uptake of radiopharmaceutical by the skeleton and absent or faint kidney images. It is thought that these appearances may be attributable to excess vitamin D, and other possible contributing factors, including the presence of renal osteodystrophy, are discussed.

Cancer imaging with CEA antibodies: historical and current perspectives.

PubMed

Goldenberg, D M

1992-01-01

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

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

A Monte Carlo study on {sup 223}Ra imaging for unsealed radionuclide therapy

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

Takahashi, Akihiko, E-mail: takahsr@hs.med.kyushu-u.ac.jp; Miwa, Kenta; Sasaki, Masayuki

Purpose: Radium-223 ({sup 223}Ra), an α-emitting radionuclide, is used in unsealed radionuclide therapy for metastatic bone tumors. The demand for qualitative {sup 223}Ra imaging is growing to optimize dosimetry. The authors simulated {sup 223}Ra imaging using an in-house Monte Carlo simulation code and investigated the feasibility and utility of {sup 223}Ra imaging. Methods: The Monte Carlo code comprises two modules, HEXAGON and NAI. The HEXAGON code simulates the photon and electron interactions in the tissues and collimator, and the NAI code simulates the response of the NaI detector system. A 3D numeric phantom created using computed tomography images of amore » chest phantom was installed in the HEXAGON code. {sup 223}Ra accumulated in a part of the spine, and three x-rays and 19 γ rays between 80 and 450 keV were selected as the emitted photons. To evaluate the quality of the {sup 223}Ra imaging, the authors also simulated technetium-99m ({sup 99m}Tc) imaging under the same conditions and compared the results. Results: The sensitivities of the three photopeaks were 147 counts per unit of source activity (cps MBq{sup −1}; photopeak: 84 keV, full width of energy window: 20%), 166 cps MBq{sup −1} (154 keV, 15%), and 158 cps MBq{sup −1} (270 keV, 10%) for a low-energy general-purpose (LEGP) collimator, and those for the medium-energy general-purpose (MEGP) collimator were 33, 13, and 8.0 cps MBq{sup −1}, respectively. In the case of {sup 99m}Tc, the sensitivity was 55 cps MBq{sup −1} (141 keV, 20%) for LEGP and 52 cps MBq{sup −1} for MEGP. The fractions of unscattered photons of the total photons reflecting the image quality were 0.09 (84 keV), 0.03 (154 keV), and 0.02 (270 keV) for the LEGP collimator and 0.41, 0.25, and 0.50 for the MEGP collimator, respectively. Conversely, this fraction was approximately 0.65 for the simulated {sup 99m}Tc imaging. The sensitivity with the LEGP collimator appeared very high. However, almost all of the counts were because of photons that penetrated or were scattered in the collimator; therefore, the proportions of unscattered photons were small. Conclusions: Their simulation study revealed that the most promising scheme for {sup 223}Ra imaging is an 84-keV window using an MEGP collimator. The sensitivity of the photopeaks above 100 keV is too low for {sup 223}Ra imaging. A comparison of the fractions of unscattered photons reveals that the sensitivity and image quality are approximately two-thirds of those for {sup 99m}Tc imaging.« less

Experimental Observations of Nuclear Activity in Deuterated Materials Subjected to a Low-Energy Photon Beam

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Benyo, Theresa L.; Pines, Vladimir; Pines, Marianna; Forsley, Lawrence P.; Westmeyer, Paul A.; Chait, Arnon; Becks, Michael D.; Martin, Richard E.; Hendricks, Robert C.;

Accelerator-based production of the (99m)Tc-(186)Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2).

PubMed

Gott, Matthew D; Hayes, Connor R; Wycoff, Donald E; Balkin, Ethan R; Smith, Bennett E; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Wilbur, D Scott; Jurisson, Silvia S

2016-08-01

Novel, natural abundance metal disulfide targets were irradiated for 1h with a 10µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

Scatter and crosstalk corrections for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators

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

Fan, Peng; Hutton, Brian F.; Holstensson, Maria

2015-12-15

Purpose: The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). Methods: A tailing model was developed to account for the low energy tail effectsmore » of the CZT detector. The parameters of the model were obtained using {sup 99m}Tc and {sup 123}I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. Results: Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of {sup 99m}Tc in dual-radionuclide imaging where there is heavy contamination from {sup 123}I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of {sup 99m}Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. Conclusions: The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.« less

Development and Optimization of a Dedicated, Hybrid Dual-Modality SPECT-CmT System for Improved Breast Lesion Diagnosis

DTIC Science & Technology

2008-01-01

CT contrast agent, four 6.0mm nylon balls (Small Parts, Inc. Miami Lakes, FL) soaked in aqueous 99mTc-pertechnetate were used as markers and taped ...Inc, Miramar, Fl) were soaked in concentrated aqueous 99mTc and taped to the exterior surface of the breast phantom to act as fiducial markers for...vol. 21, pp. 48-55, 2006. [16] H. Erdogan and J. A. Fessler, "Ordered subsets algorithms for transmission tomography," Phys Med Biol, vol. 44, pp

Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia.

PubMed Central

Neary, D; Snowden, J S; Shields, R A; Burjan, A W; Northen, B; MacDermott, N; Prescott, M C; Testa, H J

1987-01-01

Single photon emission tomographic imaging of the brain using 99mTc HM-PAO was carried out in patients with a clinical diagnosis of Alzheimer's disease, non-Alzheimer frontal-lobe dementia, and progressive supranuclear palsy. Independent assessment of reductions in uptake revealed posterior hemisphere abnormalities in the majority of the Alzheimer group, and selective anterior hemisphere abnormalities in both other groups. The findings were consistent with observed patterns of mental impairment. The imaging technique has potential value in the differential diagnosis of primary cerebral atrophy. Images PMID:3499484

99mTc MDP SPECT-CT-Based Modified Mirels Classification for Evaluation of Risk of Fracture in Skeletal Metastasis: A Pilot Study.

PubMed

Riaz, Saima; Bashir, Humayun; Niazi, Imran Khalid; Butt, Sumera; Qamar, Faisal

2018-06-01

Mirels' scoring system quantifies the risk of sustaining a pathologic fracture in osseous metastases of weight bearing long bones. Conventional Mirels' scoring is based on radiographs. Our pilot study proposes Tc MDP bone SPECT-CT based modified Mirels' scoring system and its comparison with conventional Mirels' scoring. Cortical lysis was noted in 8(24%) by SPECT-CT versus 2 (6.3%) on X-rays. Additional SPECT-CT parameters were; circumferential involvement [1/4 (31%), 1/2 (3%), 3/4 (37.5%), 4/4 (28%)] and extra-osseous soft tissue [3%]. Our pilot study suggests the potential role of SPECT-CT in predicting risk of fracture in osseous metastases.

Simultaneous 99mtc/111in spect reconstruction using accelerated convolution-based forced detection monte carlo

NASA Astrophysics Data System (ADS)

Karamat, Muhammad I.; Farncombe, Troy H.

2015-10-01

Simultaneous multi-isotope Single Photon Emission Computed Tomography (SPECT) imaging has a number of applications in cardiac, brain, and cancer imaging. The major concern however, is the significant crosstalk contamination due to photon scatter between the different isotopes. The current study focuses on a method of crosstalk compensation between two isotopes in simultaneous dual isotope SPECT acquisition applied to cancer imaging using 99mTc and 111In. We have developed an iterative image reconstruction technique that simulates the photon down-scatter from one isotope into the acquisition window of a second isotope. Our approach uses an accelerated Monte Carlo (MC) technique for the forward projection step in an iterative reconstruction algorithm. The MC estimated scatter contamination of a radionuclide contained in a given projection view is then used to compensate for the photon contamination in the acquisition window of other nuclide. We use a modified ordered subset-expectation maximization (OS-EM) algorithm named simultaneous ordered subset-expectation maximization (Sim-OSEM), to perform this step. We have undertaken a number of simulation tests and phantom studies to verify this approach. The proposed reconstruction technique was also evaluated by reconstruction of experimentally acquired phantom data. Reconstruction using Sim-OSEM showed very promising results in terms of contrast recovery and uniformity of object background compared to alternative reconstruction methods implementing alternative scatter correction schemes (i.e., triple energy window or separately acquired projection data). In this study the evaluation is based on the quality of reconstructed images and activity estimated using Sim-OSEM. In order to quantitate the possible improvement in spatial resolution and signal to noise ratio (SNR) observed in this study, further simulation and experimental studies are required.

Small Column Testing of Superlig 639 for Removal of 99Tc from Hanford Tank Waste Envelope C (Tank 241-AN-107)

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

DL Blanchard; DE Kurath; BM Rapko

The current BNFL Inc. flow sheet for pretreating Hanford High-Level tank wastes includes the use of Superlig(reg.sign)639 (SL-639) in a dual column system for removing technetium-99 ({sup 99}Tc) from the aqueous fraction of the waste. This sorbent material has been developed and supplied by IBC Advanced Technologies, Inc., American Fork, UT. This report documents the results of testing the SL-639 sorbent with diluted waste [Na{sup +}] {approx} 5 M from Tank 241-AN-107 (an Envelope C waste, abbreviated AN-107) at Battelle Northwest Laboratories (BNW). The equilibrium behavior was assessed with batch contacts between the sorbent and the waste. Two AN-107 samplesmore » were used: (1) an archived sample from previous testing and (2) a more recent sample collected specifically for BNFL. A portion of the archive sample and all of the BNFL sample were treated to remove Sr-90 and transuranic elements (TRU). All samples had also been Cs decontaminated by ion exchange (IX), and were spiked with a technetium-95m ({sup 95m}Tc) pertechnetate tracer, {sup 95m}TcO{sub 4}{sup -}.The TcO{sub 4}{sup -} and total Tc K{sub d} values, assumed equal to the {sup 95m}Tc and {sup 99}Tc K{sub d}'s, respectively, are shown in Table S1. Values are averages of duplicates, which showed significant scatter. The total Tc K{sub d} for the BNFL sample is much lower than the TcO{sub 4}{sup -}, indicating that a large fraction of the {sup 99}Tc is not pertechnetate.« less

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.

Multiple Transportable Carbohydrates During Exercise: Current Limitations and Directions for Future Research.

PubMed

Wilson, Patrick B

2015-07-01

The concept of multiple transportable carbohydrates (MTC) refers to a combination of saccharides that rely on distinct transporters for intestinal absorption. Ingestion of MTC during prolonged exercise has been purported to increase carbohydrate absorption efficiency, increase exogenous carbohydrate oxidation, reduce gastrointestinal (GI) distress, and improve athletic performance when carbohydrate intake is high (>50-60 g·h⁻¹). Although reviews of MTC research have been published previously, a comprehensive literature evaluation underscoring methodological limitations has not been conducted to guide future work. Accordingly, this review outlined the plausible mechanisms of MTC and subsequently evaluated MTC research based on several factors, including participant characteristics, exercise modality, exercise task, treatment formulation, treatment blinding, and pre-exercise nutrition status. A total of 27 articles examining MTC during exercise were identified and reviewed. Overall, ingestion of MTC led to increased exogenous carbohydrate oxidation, reduced GI distress, and improved performance during cycling lasting ≥2.5 hours, particularly when carbohydrate was ingested at ≥1.2 g·min⁻¹. Despite the apparent benefits, several limitations in the literature were apparent, including that only 3 studies used running, only 2 studies were conducted in the field, most participants were fasted, and women and adolescents were underrepresented. In addition, the majority of the studies fed carbohydrate at ≥1.2 g·min⁻¹, which may have inflated levels of GI distress and exaggerated performance decrements with single-saccharide feedings. Based on these limitations, future MTC investigations should consider focusing on running, examining team-based sports, including women and adolescents, conducting experiments under field conditions, examining the modifying effects of pre-exercise nutrition, and using modest feeding protocols (1.0-1.2 g·min⁻¹).

Removal of carbamates and detoxification potential in a biomixture: Fungal bioaugmentation versus traditional use.

PubMed

Rodríguez-Rodríguez, Carlos E; Madrigal-León, Karina; Masís-Mora, Mario; Pérez-Villanueva, Marta; Chin-Pampillo, Juan Salvador

2017-01-01

The use of fungal bioaugmentation represents a promising way to improve the performance of biomixtures for the elimination of pesticides. The ligninolyitc fungus Trametes versicolor was employed for the removal of three carbamates (aldicarb, ALD; methomyl, MTM; and methiocarb, MTC) in defined liquid medium; in this matrix ALD and MTM showed similar half-lives (14d), nonetheless MTC exhibited a faster removal, with a half-life of 6.5d. Then the fungus was employed in the bioaugmentation of an optimized biomixture to remove the aforementioned carbamates plus carbofuran (CFN). Bioaugmented and non-bioaugmented systems removed over 99% ALD and MTM after 8d of treatment, nonetheless a slight initial delay in the removal was observed in the bioaugmented biomixtures (removal after 3d: ALD 87%/97%; MTM 86%/99%, in bioaugmented/non-bioaugmented systems). The elimination of the other carbamates was slower, but independent of the presence of the fungus: >98% for MTM after 35d and >99.5% for CFN after 22d. Though the bioaugmentation did not improve the removal capacity of the biomixture, it favored a lower production of transformation products at the first stages of the treatment, and in both cases, a marked decrease in the toxicity of the matrix was swiftly achieved along the process (from 435 to 448 TU to values <1TU in 16d). Copyright © 2016 Elsevier Inc. All rights reserved.

Carbachol improves the secretion of transplanted submandibular glands during the latent period after microvascular autologous transplantation for severe keratoconjunctivitis sicca.

PubMed

Liu, X-J; Li, M; Su, J-Z; Wang, Z; Xie, Z; Yu, G-Y

2016-10-01

Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2mg/2ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m ((99m)Tc) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9min and the duration of action from 50 to 110min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P<0.01). (99m)Tc scintigraphy showed a decline in the dynamic time-activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Assessing the growth of preterm infants using detailed anthropometry.

PubMed

Ashton, James J; Johnson, Mark J; Pond, Jenny; Crowley, Philippa; Dimitrov, Borislav D; Pearson, Freya; Beattie, R Mark

2017-06-01

Preterm infants display altered body composition compared to term infants, and weight gain is a crude indicator body composition. Childhood mid-upper arm circumference (MUAC) is a measure of nutritional status. This study investigates MUAC and mid-thigh circumference (MTC) to monitor growth in preterm infants. Preterm infants (<30-week gestation) were recruited. MUAC, MTC, weight, length and head circumference (HC) were measured at recruitment and weekly intervals until discharge. Descriptive, correlation and regression analyses were used. Ninety-three infants were recruited. Median measurement duration was eight weeks (1-19). Median gestational age was 27 weeks (23-29). Analysis by curve estimation displayed a mean increase of 2.58 mm/week (left MUAC) (p ≤ 0.0001), 2.56 mm/week (right MUAC) (p ≤ 0.0001), 4.16 mm/week (left MTC) (p ≤ 0.0001), 4.20 mm/week (right MTC) (p ≤ 0.0001). Coefficients of determination (R 2 ) were calculated using a growth regression model for MUAC and MTC (0.866-0.917); measures were comparable to growth modelling of weight (0.913), length (0.945) and HC (0.928). High concordance between left and right MUAC and MTC generated a Pearson's correlation coefficient of 0.999 (MUAC) (p ≤ 0.001) and 0.994 (MTC) (p ≤ 0.001). Data demonstrate the potential utility of MUAC and MTC as additional measures of growth in preterm infants that are reproducible over time. There is potential to gain insights to improve lean-mass accretion in preterm infants. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

True-coincidence correction when using an LEPD for the determination of the lanthanides in the environment via k0-based INAA.

PubMed

Freitas, M C; De Corte, F

1994-01-01

As part of a recent study on the environmental effects caused by the operation of a coal-fired power station at Sines, Portugal, k0-based instrumental neutron activation analysis (INAA) was used for the determination of the lanthanides (and also of tantalum and uranium) in plant leaves and lichens. In view of the accuracy and sensitivity of the determinations, it was advantageous to make use of a low-energy photon detector (LEPD). To begin with, in the present article, a survey is given of the former developments leading to user-friendly procedures for detection efficiency calibration of the LEPD and for correction for true-coincidence (cascade summing) effects. As a continuation of this, computer coincidence correction factors are now tabulated for the relevant low-energetic gamma-rays of the analytically interesting lanthanide, tantalum, and uranium radionuclides. Also the 140.5-keV line of 99Mo/99mTc is included, molybdenum being the comparator chosen when counting using an LEPD.

p-Tertbutylcalix[4]arene nanoemulsion: preparation, characterization and comparative evaluation of its decontamination efficacy against Technetium-99m, Iodine-131 and Thallium-201.

PubMed

Rana, Sudha; Sharma, Navneet; Ojha, Himanshu; Shivkumar, Hosakote Gurumalappa; Sultana, Sarwat; Sharma, Rakesh Kumar

2014-05-01

This study aimed to develop p-tertbutylcalix[4]arene o/w nanoemulsion for decontamination of radioisotopes from skin. Formulation was characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), multi-photon confocal microscopy techniques and in vitro dissolution studies. In vivo evaluation of nano-emulsion was done using nuclear medicine technique. Stability studies and dermal toxicity studies were also carried out. Comparative decontamination efficacy (DE) studies were performed on synthetic human tissue equivalent material and Sprague Dawley rat against three commonly used medical radioisotopes, i.e., Technetium-99m ((99m)Tc), Iodine-131 ((131)I) and Thallium-201 ((201)Tl). Decontamination was performed using cotton swabs soaked in nanoemulsion at different time intervals of contaminants exposure. Whole body imaging and static counts were recorded using gamma camera before and after each decontamination attempt data was analyzed using one way analysis of variance (ANOVA) and found to be statistically significant (p<0.05). DE of the nanoemulsion loaded with p-tertbutylcalix[4]arene was observed to be 88±5%, 90±3% and 89±3% for (99m)Tc, (131)I and (201)Tl respectively. Dermal toxicity studies revealed no significant differences between treated and control animals. Skin histopathology slides with and without API (Active pharmaceutical ingredients) also found to be comparable. p-Tertbutylcalix[4]arene loaded nanoemulsion shows great promise for skin decontamination against broad ranges of radiological contaminants besides being stable and safe. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Preparation and biological evaluation of [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide for somatostatin receptor-positive tumor imaging.

PubMed

Erfani, Mostafa; Shafiei, Mohammad; Mazidi, Mohammad; Goudarzi, Mostafa

2013-04-01

Somatostatin-derived analogues play an important role in the diagnosis and treatment of neuroendocrine tumors. The aim of this study was to evaluate a new somatostatin analogue designed for labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), β-(3-benzothienyl)-Ala (BzThi(3))]-octreotide ([HYNIC]-BOC), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was performed on a solid phase using a standard Fmoc strategy. The HYNIC-peptide conjugate was radiolabeled with (99m)Tc and characterized by ITLC and high-performance liquid chromatography (HPLC). In vitro studies were carried out in sstr2 expressing AR4-2J cell lines. In vivo distribution studies were performed in rats bearing the AR4-2J tumor. The radiolabeled complex could be prepared at high-specific activities and >95% radiochemical yield as determined by HPLC. The peptide conjugate showed high-affinity binding for sstr2. The radioligand showed high and specific internalization into AR4-2J cells (18.19%±0.21% at 4 hours). In vivo distribution studies in rats bearing tumor have shown a receptor-specific uptake of radioactivity in somatostatin receptor-positive organs. After 4 hours, uptake in the AR4-2J tumor was 1.71%±0.36% injected dose per gram tissue (%ID/g). These data show that [(99m)Tc/EDDA/Tricine/HYNIC(0), BzThi(3)]-octreotide is a specific radioligand for the somatostatin receptor-positive tumors and is a suitable candidate for clinical studies.

High radioactive concentration of 99mTc from a zirconium [99Mo]molybdate gel generator using an acidic alumina column for purification and concentration.

PubMed

Sarkar, S K; Saraswathy, P; Arjun, G; Ramamoorthy, N

2004-06-01

Newer applications of radiopharmaceuticals in nuclear medicine require pertechnetate of moderate to high radioactive concentration. Hence there is a need to develop simple procedures for the concentration of pertechnetate, and such a procedure is given in this paper. Ten to 20 ml of sodium [Tc]pertechnetate eluted in de-ionized water from a zirconium [Mo]molybdate (ZrMo) gel column generator was passed through 2 g of an acidic alumina bed (35 x 8 mm) in order to remove the co-eluted traces of Mo and to retain the pertechnetate. The retained pertechnetate was then re-eluted, quantitatively, in 3 ml of normal saline, from the alumina column. About a 4-fold increase in radioactive concentration of Tc was obtained (cf. approximately 10-12 ml normal saline is required for the elution of Tc from the gel column). Generators containing up to 22.2 GBq (600 mCi) Mo in 6-7 g ZrMo gel column (35 x 13 mm) were prepared and a radioactive concentration of Tc up to 4 GBq x ml (110 mCi x ml) was obtained on the first day of use. The overall recovery of Tc was >90%, Mo breakthrough was 10 to 10% and the duration of concentration was 3-5 min. The chemical impurity in terms of Al, Mo and Zr was <10 ppm each. The same procedure for the concentration of pertechnetate was applied to generators with 12-15 g ZrMo gel beds to obtain a higher capacity Tc gel generator, with similar findings.

Enhanced detection of tuberculous mycobacteria in animal tissues using a semi-nested probe-based real-time PCR.

PubMed

Costa, Pedro; Ferreira, Ana S; Amaro, Ana; Albuquerque, Teresa; Botelho, Ana; Couto, Isabel; Cunha, Mónica V; Viveiros, Miguel; Inácio, João

2013-01-01

Bovine tuberculosis has been tackled for decades by costly eradication programs in most developed countries, involving the laboratory testing of tissue samples from allegedly infected animals for detection of Mycobacterium tuberculosis complex (MTC) members, namely Mycobacterium bovis. Definitive diagnosis is usually achieved by bacteriological culture, which may take up to 6-12 weeks, during which the suspect animal carcass and herd are under sanitary arrest. In this work, a user-friendly DNA extraction protocol adapted for tissues was coupled with an IS6110-targeted semi-nested duplex real-time PCR assay to enhance the direct detection of MTC bacteria in animal specimens, reducing the time to achieve a diagnosis and, thus, potentially limiting the herd restriction period. The duplex use of a novel β-actin gene targeted probe, with complementary targets in most mammals, allowed the assessment of amplification inhibitors in the tissue samples. The assay was evaluated with a group of 128 fresh tissue specimens collected from bovines, wild boars, deer and foxes. Mycobacterium bovis was cultured from 57 of these samples. Overall, the full test performance corresponds to a diagnostic sensitivity and specificity of 98.2% (CIP95% 89.4-99.9%) and 88.7% (CIP95% 78.5-94.7%), respectively. An observed kappa coefficient was estimated in 0.859 (CI P95% 0.771-0.948) for the overall agreement between the semi-nested PCR assay and the bacteriological culture. Considering only bovine samples (n = 69), the diagnostic sensitivity and specificity were estimated in 100% (CIP95% 84.0-100%) and 97.7% (CIP95% 86.2-99.9%), respectively. Eight negative culture samples exhibiting TB-like lesions were detected by the semi-nested real-time PCR, thus emphasizing the increased potential of this molecular approach to detect MTC-infected animal tissues. This novel IS6110-targeted assay allows the fast detection of tuberculous mycobacteria in animal specimens with very high sensitivity and specificity, being amenable and cost effective for use in the routine veterinary diagnostic laboratory with further automation possibilities.

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

PubMed

Monzani, F; Del Guerra, P; Caraccio, N; Casolaro, A; Lippolis, P V; Goletti, O

1997-05-01

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

Scintigraphic results in patients with lung transplants: a prospective comparative study.

PubMed

Humplik, B I; Sandrock, D; Aurisch, R; Richter, W-St; Ewert, R; Munz, D L

2005-04-01

We addressed the feasibility of scintigraphy in the postoperative monitoring of lung transplants. 37 patients (22 women, 15 men, 37 +/- 15 years) in good clinical condition were examined after lung transplantation. Scintigraphic procedures for assessing ventilation (133Xe), perfusion (99mTc microspheres) and aerosol-inhalation (99mTc aerosol) were performed for all patients. The findings were compared with those of established diagnostic modalities. All lung transplants showed homogeneous ventilation but with a non-physiologic difference of over 20% between both pulmonary lobes in one-third of the cases. There was a difference between the impairement of perfusion and ventilation in the presence of an impaired Euler-Liljestrand reflex in 14/37 (38%) patients. Furthermore, bronchoscopy and aerosol-inhalation scans often did not correlate, e. g. a bronchoscopically evident stenosis was not necessarily associated with an increased activity, and vice versa. Although peripheral mucociliary clearance was preserved after transplantation, stasis in central airways resulted in significantly impaired global clearance. Ventilation and perfusion scintigraphy reveal in a significant number of lung recipients pathologic findings and therefore can be recommended for postoperative monitoring. From a clinical point of view aerosol-inhalation scintigraphy (clearance) is not of any additional value.

RET fusion as a novel driver of medullary thyroid carcinoma.

PubMed

Grubbs, Elizabeth G; Ng, Patrick Kwok-Shing; Bui, Jacquelin; Busaidy, Naifa L; Chen, Ken; Lee, Jeffrey E; Lu, Xinyan; Lu, Hengyu; Meric-Bernstam, Funda; Mills, Gordon B; Palmer, Gary; Perrier, Nancy D; Scott, Kenneth L; Shaw, Kenna R; Waguespack, Steven G; Williams, Michelle D; Yelensky, Roman; Cote, Gilbert J

2015-03-01

Oncogenic RET tyrosine kinase gene fusions and activating mutations have recently been identified in lung cancers, prompting initiation of targeted therapy trials in this disease. Although RET point mutation has been identified as a driver of tumorigenesis in medullary thyroid carcinoma (MTC), no fusions have been described to date. We evaluated the role of RET fusion as an oncogenic driver in MTC. We describe a patient who died from aggressive sporadic MTC < 10 months after diagnosis. Her tumor was evaluated by means of next-generation sequencing, including an intronic capture strategy. A reciprocal translocation involving RET intron 12 was identified. The fusion was validated using a targeted break apart fluorescence in situ hybridization probe, and RNA sequencing confirmed the existence of an in-frame fusion transcript joining MYH13 exon 35 with RET exon 12. Ectopic expression of fusion product in a murine Ba/F3 cell reporter model established strong oncogenicity. Three tyrosine kinase inhibitors currently used to treat MTC in clinical practice blocked tumorigenic cell growth. This finding represents the report of a novel RET fusion, the first of its kind described in MTC. The finding of this potential novel oncogenic mechanism has clear implications for sporadic MTC, which in the majority of cases has no driver mutation identified. The presence of a RET fusion also provides a plausible target for RET tyrosine kinase inhibitor therapies.

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

Comparison of 18F SPECT with PET in myocardial imaging: a realistic thorax-cardiac phantom study.

PubMed

Knešaurek, Karin; Machac, Josef

2006-10-31

Positron emission tomography (PET) imaging with fluorine-18 (18F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 (82Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive 18F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to 18F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of 18F and 22.2 MBq of Technetium-99m (99mTc) in the SPECT study and with 7.4 MBq of 18F and 370 MBq of 82Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. The contrast for 3 cm, 2 cm and 1 cm inserts were for 18F PET data, 1.0 +/- 0.01, 0.67 +/- 0.02 and 0.25 +/- 0.01, respectively. For 82Rb PET data, the corresponding contrast values were 0.61 +/- 0.02, 0.37 +/- 0.02 and 0.19 +/- 0.01, respectively. For 18F SPECT the contrast values were, 0.31 +/- 0.03 and 0.20 +/- 0.05 for 3 cm and 2 cm inserts, respectively. For 99mTc SPECT the contrast values were, 0.63 +/- 0.04 and 0.24 +/- 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". For smaller defects the 99mTc/18F SPECT imaging cannot entirely replace the more expensive 82Rb/18F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast.

Monitoring Radionuclide Transport and Spatial Distribution with a 1D Gamma-Ray Scanner

NASA Astrophysics Data System (ADS)

Dozier, R.; Erdmann, B.; Sams, A.; Barber, K.; DeVol, T. A.; Moysey, S. M.; Powell, B. A.

2016-12-01

Understanding radionuclide movement in the environment is important for informing strategies for radioactive waste management and disposal. A 1-dimensional (1D) gamma-ray emission scanning system was developed to investigate radionuclide transport behavior within soils. Two case studies illustrate the use of the system for non-destructively monitoring transport processes within a soil column. The first case study explores the system capabilities for simultaneously detecting technetium-99m (99mTc), iodine-131 (131I), and sodium-22 (22Na) moving through a column (length = 14.1 cm, diameter = 3.8 cm) packed with soil from the Department of Energy's Savannah River Site. A sodium iodide (NaI) detector was placed at 4 cm above the influent and a Bismuth germanate (BGO) detector at about 10 cm above the influent. The NaI detector results show 99mTc, 131I, and 22Na having similar breakthrough curves with the tail of 99mTc being lower than that of 131I and 22Na. NaCl tracer results compliment the gamma-ray emission measurements. These results are promising because we are able to monitor movement of the isotopes in the column in real-time. In the second case study, the 1D gamma scanner was used to quantify radionuclide mobility within a lysimeter (length = 51 cm, diameter = 10 cm). A cementitious waste form containing cobalt-60 (60Co), barium-133 (133Ba), cesium-137 (137Cs), and europium-152 (152Eu), with the amount of each contained in the cement ranging from 3 to 8.5 MBq, was placed at the midpoint of the lysimeter. The lysimeter was then exposed to natural rainfall and environmental conditions and effluent samples were collected and quantified on a quarterly basis. Following 3.3 years of exposure, the radionuclide distribution in the lysimeter was quantified with a 0.64 cm collimated high-purity germanium gamma-ray spectrometer. Diffusion of 137Cs away from the cementitious wasteform was observed. No movement was seen for 133Ba, 60Co, or 152Eu within the detection limits of the spectrometer. An activity balance was used to quantify the detection efficiency of the spectrometer as a function of gamma-ray energy.

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.

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.

Medical Isotope Production Analyses In KIPT Neutron Source Facility

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

Talamo, Alberto; Gohar, Yousry

Medical isotope production analyses in Kharkov Institute of Physics and Technology (KIPT) neutron source facility were performed to include the details of the irradiation cassette and the self-shielding effect. An updated detailed model of the facility was used for the analyses. The facility consists of an accelerator-driven system (ADS), which has a subcritical assembly using low-enriched uranium fuel elements with a beryllium-graphite reflector. The beryllium assemblies of the reflector have the same outer geometry as the fuel elements, which permits loading the subcritical assembly with different number of fuel elements without impacting the reflector performance. The subcritical assembly is drivenmore » by an external neutron source generated from the interaction of 100-kW electron beam with a tungsten target. The facility construction was completed at the end of 2015, and it is planned to start the operation during the year of 2016. It is the first ADS in the world, which has a coolant system for removing the generated fission power. Argonne National Laboratory has developed the design concept and performed extensive design analyses for the facility including its utilization for the production of different radioactive medical isotopes. 99Mo is the parent isotope of 99mTc, which is the most commonly used medical radioactive isotope. Detailed analyses were performed to define the optimal sample irradiation location and the generated activity, for several radioactive medical isotopes, as a function of the irradiation time.« less

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.

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.

Radioisotope scanning in osseous sarcoidosis

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

Rohatgi, P.K.

1980-01-01

Technetium-99m (/sup 99m/Tc)-labeled pyrophosphate or diphosphonate compounds and gallium-67 citrate (/sup 67/Ga) are two radionuclide scanning agents that are in widespread use in clinical practice. Technetium-99m pyrophosphate is used extensively for bone scanning to detect metastatic bone disease, benign bone tumors, osteomyelitis, benign hypertrophic osteoarthropathy, and Paget's disease. Only two reports describe abnormal /sup 99m/Tc/ pyrophosphate bone scans in four patients with osseous sarcoidosis. Gallium-67 scans are used primarily to localize neoplastic or inflammatory lesions anywhere in the body. In recent years /sup 67/Ga scans have also been used to detect the presence of both pulmonary and extrapulmonary sarcoidosis, butmore » there are no reports describing abnormal uptake of gallium in patients with osseous sarcoidosis. This report describes experience with radioisotope scanning in two patients with osseous sarcoidosis.« less

Direct Imaging of Radionuclide-Produced Electrons and Positrons with an Ultrathin Phosphor

PubMed Central

Chen, Liying; Gobar, Lisa S.; Knowles, Negar G.; Liu, Zhonglin; Gmitro, Arthur F.; Barrett, Harrison H.

2008-01-01

Current electron detectors are either unable to image in vivo or lack sufficient spatial resolution because of electron scattering in thick detector materials. This study was aimed at developing a sensitive high-resolution system capable of detecting electron-emitting isotopes in vivo. Methods The system uses a lens-coupled charge-coupled-device camera to capture the scintillation light excited by an electron-emitting object near an ultrathin phosphor. The spatial resolution and sensitivity of the system were measured with a 3.7-kBq 90Y/90Sr β-source and a 70-µm resin bead labeled with 99mTc. Finally, we imaged the 99mTc-pertechnetate concentration in the mandibular gland of a mouse in vivo. Results Useful images were obtained with only a few hundred emitted β particles from the 90Y/90Sr source or conversion electrons from the 99mTc bead source. The in vivo image showed a clear profile of the mandibular gland and many fine details with exposures of as low as 30 s. All measurements were consistent with a spatial resolution of about 50 µm, corresponding to 2.5 detector pixels with the current camera. Conclusion Our new electron-imaging system can image electron-emitting isotope distributions at high resolution and sensitivity. The system is useful for in vivo imaging of small animals and small, exposed regions on humans. The ability to image β particles, positrons, and conversion electrons makes the system applicable to most isotopes. PMID:18552136

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

An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers.

PubMed

Varmira, Kambiz; Hosseinimehr, Seyed Jalal; Noaparast, Zohreh; Abedi, Seyed Mohammad

2014-02-01

Human epidermal growth factor receptor 2 (HER2) expression has been shown to be increased in several types of human tumours. In this study, for the imaging of HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. Stability testing of the radiolabelled aptamers in the serum was performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its biodistribution properties were assessed in normal and SKOV-3 tumour-bearing mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were labelled with (99m)Tc at a high yield and radiochemical purity. Cellular experiments confirmed the specific binding of the RNA aptamer to the HER2 receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that of the aptamer with tricine. Tumours also showed a higher accumulation of radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which can be a potential tool for the molecular imaging of HER2-overexpressing cancers.

Primary septic arthritis of the manubriosternal joint in a heroin user

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

Lopez-Longo, F.J.; Monteagudo, I.; Vaquero, F.J.

1986-01-01

A 20-year-old heroin user developed staphylococcus septic arthritis of the manubrium joint. The diagnosis was established by a culture of the infected tissue and blood culture. The clinical impression was aided by 99mTc radionuclide scintimetry. Early diagnosis localized the infection. Immediate antibiotic therapy solved a problem in the sternum that seems not to have been reported in the English literature.

High Resolution Pre-Clinical CT and SPECT Imaging Techniques for Investigating Flow and Transport Mechanisms in Porous Media

NASA Astrophysics Data System (ADS)

Dogan, M.; Moysey, S. M.; Mamun, A. A.; DeVol, T. A.; Powell, B. A.; Murdoch, L. C.

2017-12-01

Single Photon Emission Computed Tomography (SPECT) and x-ray Computed Tomography (CT) are both high-resolution imaging methods for investigating laboratory scale samples. We have recently conducted several experiments to determine the capabilities of two preclinical imaging systems; the imaging resolution of the two systems studied were found to be 0.2 mm for CT and 2-4 mm for SPECT depending on the tracer and scan times. While the resolution of these instruments is not sufficient for imaging the pore structure of most soils, it is sufficient to resolve macropore structures such as cracks and root channels and to observe their impact on transport. For example, we have used CT scans to monitor the formation of desiccation cracks within soils obtained from the Savannah River Site. We were then able to observe the interaction between the crack network and pore matrix during an infiltration experiment by spiking the infiltrating water with an iodide contrast agent as a tracer. We found a complex interaction between the flow systems, where flow shifted from matrix dominated at low flow rates to macropore dominated at high flow rates. SPECT imaging is capable of monitoring the distribution of gamma-ray emitting radionuclides in 3D. It is therefore also a useful tool for monitoring transport processes, but is particularly powerful when a redox sensitive isotope like 99mTc is used as the tracer. We show an example of a transport experiment where a 99mTc solution is passed through a column containing zones with different redox properties, i.e., a zone amended with titanomagnetite, another with anatase, and a third with silica flour. The 99mTc is captured by the strongly reducing materials, but not the zone with silica flour. The example illustrates how these imaging modalities can be used to discriminate between chemical and physical processes controlling fate and transport of the radionuclide. In particular, CT and SPECT can be used to image contaminant transport in lab scale columns by combining the structural information obtained from CT with the concentration distributions from SPECT.

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors.

PubMed

Gandomkar, Mostafa; Najafi, Reza; Shafiei, Mohammad; Mazidi, Mohammad; Ebrahimi, Sayed Esmaeil Sadat

2007-08-01

Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.

Hereditary medullary thyroid carcinoma: the management dilemma.

PubMed

Zhou, Ping; Liu, Jian; Cheng, Shao-Wen; Wang, Bing; Yang, Rong; Peng, Ling

2012-06-01

Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25-30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype-phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.

Improvements in quality of care resulting from a formal multidisciplinary tumour clinic in the management of high-grade glioma.

PubMed

Back, Michael F; Ang, Emily L L; Ng, Wai-Hoe; See, Siew-Ju; Lim, C C Tchoyoson; Tay, Lee-Lee; Yeo, Tseng-Tsai

2007-05-01

There is increasing belief that a formal protocol-based multidisciplinary care model should be adopted as an optimal care model in oncology. However, there is minimal outcome evidence to demonstrate an improvement in patient care. The aim of this study was to compare clinical quality outcomes between patients with high-grade glioma managed at one hospital using a formal neuro-oncology multidisciplinary tumour clinic (MTC) and a second hospital with a traditional on-call referral pattern (non-MTC). Patients with high-grade glioma managed radically with radiation therapy at 2 Singapore hospitals from May 2002 to May 2006 were entered into a prospective database. Patients were grouped into management via MTC or non-MTC. Four clinical quality indicators were chosen retrospectively to assess the variation in practice: a) Use of computed tomography (CT) or magnetic resonance (MR) imaging post-resection (POI) for assessment of residual disease; b) Commencement of radiation therapy (RT) within 28 days of surgery; c) Adjuvant chemotherapy use for glioblastoma multiforme (CTGBM) and d) Median survival. Sixty-seven patients were managed radically, with 47 by MTC and by 20 by non-MTC. MTC patients were more likely to have POI (P = 0.042), and CTGBM (P = 0.025). Although the RT start time was similar for the whole cohort (60% versus 45%: P = 0.296); for GBM patients, the RT start was earlier (63% vs 33% P = 0.024). The median survival for the MTC group was 18.7 months versus 11.9 months for the non-MTC group (P = 0.11). Clinical quality outcomes were significantly improved in patients with high-grade glioma managed in this neuro-oncology MTC.

Intratumoral Injection of 188Re labeled Cationic Polyethylenimine Conjugates: A Preliminary Report

PubMed Central

Kim, Eun-Mi; Heo, Young-Jun; Moon, Hyung-Bae; Bom, Hee-Seung; Kim, Chang-Guhn

2004-01-01

188Re(Rhenium) is easily obtained from an in-house 188W/188Re generator that is similar to the current 99Mo/99mTc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of 188Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of 188Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, 188Re perrhenate) were injected directly into the tumors. There were increases in the retention of 188Re inside the tumor when PEI was incorporated with 188Re compared to the use of free 188Re. The 188Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that 188Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support 188Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection. PMID:15483337

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

PubMed

Le, Van So; Do, Zoe Phuc-Hien; Le, Minh Khoi; Le, Vicki; Le, Natalie Nha-Truc

2014-06-10

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

Polymorphisms of 20 regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis.

PubMed

Bigi, María M; Blanco, Federico Carlos; Araújo, Flabio R; Thacker, Tyler C; Zumárraga, Martín J; Cataldi, Angel A; Soria, Marcelo A; Bigi, Fabiana

2016-08-01

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans and animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and other members of the MTC evolved. The genome of M. bovis is over >99.95% identical to that of M. tuberculosis but with seven deletions ranging in size from 1 to 12.7 kb. In addition, 1200 single nucleotide mutations in coding regions distinguish M. bovis from M. tuberculosis. In the present study, we assessed 75 M. tuberculosis genomes and 23 M. bovis genomes to identify non-synonymous mutations in 202 coding sequences of regulatory genes between both species. We identified species-specific variants in 20 regulatory proteins and confirmed differential expression of hypoxia-related genes between M. bovis and M. tuberculosis. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent.

PubMed

Mohammadgholi, Mohsen; Sadeghzadeh, Nourollah; Erfani, Mostafa; Abediankenari, Saeid; Abedi, Seyed Mohammad; Emrarian, Iman; Jafari, Narjes; Behzadi, Ramezan

2018-01-01

Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

PubMed

Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

2004-08-01

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

Assessment of the viability of skin grafts

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

Wahner, H.W.

1988-07-01

A number of tests are available to monitor the blood flow in free and distant pedicle skin grafts. The information from these tests aids in the development of measures to enhance vascularization and is occasionally needed to make clinical decisions in patients with distant pedicle grafts. Measurements of the disappearance of an intradermally injected small amount of /sup 133/Xe allows determination of a clearance rate and blood flow before and after clamping the original blood supply through the base. With /sup 99m/Tc, which is generally more readily available, a flow index and block index can be determined. Clinically both proceduresmore » give equally good results in determining a safe time for pedicle base separation. The fluorescein test allows assessment of regional blood flow distribution within the pedicle.« less

Scintigraphic evaluation of digital circulation during the developmental and acute phases of equine laminitis

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

Trout, D.R.

1987-01-01

Using nuclear isotopic imaging, digital circulation was sequentially evaluated at 24-hour intervals in 11 control horses and in 9 horses affected with acute laminitis, created by administration of a high-starch ration. Following intra-arterial injection of /sup 99m/Tc macroaggregated albumin into the brachiocephalic trunk, a gamma camera and dedicated nuclear medicine computer were used to acquire static images of the right front foot. Dynamic vascular-phase and static interstitial-phase images were also obtained after jugular vein injection of /sup 99m/Tc diethylenetriamine pentaacetic acid. These procedures were performed on standing horses, using either minimal or no tranquilization. The images were quantitatively analyzed formore » parameters indicative of circulation to the foot as a whole and to specific regions of interest within the foot. There was no evidence of reduced total blood flow to the lamellae during either the developmental or acute phases of laminitis. Although total flow tended to increase throughout the peripheral/external regions of the foot, statistically significant elevations were consistently present only within the lamellae. Changes indicative of decreased total blood flow were noted in the central/internal regions of the foot. These alterations usually occurred coincident with or after the onset of clinical lameness.« less

The uterine blush. A potential false-positive in Meckel's scan interpretation

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

Fink-Bennett, D.

To determine the presence, prevalence, and clinical importance of /sup 99m/Tc pertechnetate uterine uptake, this retrospective analysis of 71 Meckel's scans was undertaken. Specifically, each study was evaluated for the presence of a focal accumulation of radiotracer cephalad to the bladder. Patients received an intravenous dose of 150 microCi/kg of /sup 99m/Tc pertechnetate. Each study consisted of 15 one minute anterior serial gamma camera images, and a 15, 30, and 60 minute anterior, right lateral and posterior scintiscan. Menstrual histories were obtained from all patients except two. No males (33/33), nor premenstrual (13/13), menopausal (4/4) or posthysterectomy (2/2) patients revealedmore » a uterine blush. Eleven of 15 patients (73%) with regular menses demonstrated a uterine blush. They were in the menstrual or secretory phases of their cycle. Four demonstrated no uterine uptake, had regular periods, but were in the proliferative phase of their cycle. Two with irregular periods, and one with no recorded menstrual history, manifested the blush. Radiotracer should be expected in the uterus during the menstrual and secretory phases of the menstrual cycle. It is a manifestation of a normal physiologic phenomenon, and must be recognized to prevent false-positive Meckel's scan interpretations.« less

Evaluation of a Simple in-House Test to Presumptively Differentiate Mycobacterium tuberculosis Complex from Nontuberculous Mycobacteria by Detection of p-Nitrobenzoic Acid Metabolites

PubMed Central

Wang, Guirong; Yu, Xia; Liang, Qian; Chen, Suting; Wilson, Stuart; Huang, Hairong

2013-01-01

The timely differentiation of Mycobacterium tuberculosis complex (MTC) and non-tubercular mycobacterium (NTM) species is urgently needed in patient care since the routine laboratory method is time consuming and cumbersome. An easy and cheap method which can successfully distinguish MTC from NTM was established and evaluated. 38 mycobacterial type and reference strains and 65 clinical isolates representing 10 species of mycobacterium were included in this study. Metabolites of p-nitrobenzoic acid (PNB) reduction were identified using liquid chromatography and tandem mass spectrometry (LC/MS/MS). A spectrophotometric method was developed to detect these metabolites, which was evaluated on a number of MTC and NTM species. All of the tested NTM species and strains reduced PNB to p-aminobenzoic acid (PABA), while none of the MTC strains showed a similar activity. Spectrophotometric detection of PABA had 100% sensitivity and specificity for MTC and NTM differentiation among the type strains and the clinical isolates tested. PABA was identified as one of the metabolites of PNB reduction. All the tested NTM species metabolized PNB to PABA whereas the MTC members lacked this activity. A simple, specific and cost-effective method based on PABA production was established in order to discriminate MTC from NTM from cultured organisms. PMID:24260497

Direct Quantification of Post-Stress-Rest Left Ventricular Motion and Thickening Changes for Myocardial Perfusion SPECT

PubMed Central

Karimi-Ashtiani, Shahryar; Arsanjani, Reza; Fish, Mathews; Kavanagh, Paul; Germano, Guido; Berman, Daniel; Slomka, Piotr

2012-01-01

Changes in myocardial wall motion and thickening during myocardial perfusion single-photon emission computed tomography (MPS) are typically assessed separately from gated studies to assess for stress induced functional abnormalities. We sought to develop and validate a novel approach for automatic quantification of post-stress-rest myocardial motion and thickening changes (MTC). Methods Endocardial surfaces at the end-diastolic and end-systolic frames for post-stress and rest studies were registered automatically to each other by matching ventricular surfaces. Myocardial MTCs were computed and normal limits of change were determined as the mean and standard deviation for each polar sample. Normal limits were utilized to quantify the MTCs for each map and the accumulated sample values were used for abnormality assessments in segmental regions. A hybrid method was devised by combining the Total Perfusion Deficit (TPD) and MTC for each vessel territory. Normal limits were obtained from 100 subjects with low likelihood (LLK) of coronary artery disease (CAD). For validation, 623 subjects with correlating invasive angiography were studied. All subjects had a stress/rest 99mTc-sestamibi exercise or adenosine test, and all had coronary angiography within 3 months of MPS. All MTC and TPD measurements were derived automatically. The diagnostic accuracy for detection of coronary artery disease for MTC+TPD was compared to TPD alone. Results Segmental normal values for motion change were between −1.3 and −4.1 mm and between −30.1% and −9.8% for thickening change. MTC combined with TPD achieved 61% sensitivity for 3-vessel disease (3VD), 63% for 2-vessel disease (2VD), and 90% for 1-vessel disease (1VD) detection vs. 32% for 3VD (P <0.0001), 53% for 2VD (P < 0.001), and 90% for 1VD (P = 1.0) detection with TPD alone method. The specificity for the combined method was 71% for 3VD, 72% for 2VD, and 47% for 1 VD detection vs. 90% for 3VD (P < 0.0001), 80% for 2VD (P <0.001), and 50% for 1VD detection (P=0.0625) for TPD alone method. The accuracy of 3VD detection by MTC+TPD was higher (69%) than the accuracy of TPD + change in ejection fraction (63%), (P< 0.004). Conclusion We established normal limits and a novel method for computation of regional functional changes between post-stress and rest. Combination of (TPD) with MTC improved the sensitivity for the detection of 3VD and 2VD as compared to TPD alone. PMID:22872739

Chimeric autologous/allogeneic constructs for skin regeneration.

PubMed

Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

2014-08-01

The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

A new approach to the analysis of radiopharmaceuticals. Final technical report, January 15, 1987--June 30, 1991

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

Jones, A.G.; Davison, A.; Costello, C.E.

The objective of this research was to investigate analytical techniques that could be used in the study of both the basic chemistry and the radiopharmaceutical chemistry of {sup 99m}Tc. First funded in 1981, the work focused initially upon the use of high performance liquid chromatography (HPLC) and various forms of mass spectrometry for the identification of technetium species. This funding allowed the authors to combine HPLC and mass spectrometry to identify radiopharmaceuticals which, although in clinical use, had not previously been characterized. Other techniques that have been examined include resonance Raman spectroscopy and, more significantly, {sup 99}Tc nuclear magnetic resonancemore » spectroscopy (NMR), with the latter not only being used in purely chemical experiments but also in biologic studies. In 1985 a grant to the Department of Chemistry at MIT from DOE allowed the purchase of an X-ray diffractometer and access to this instrument has enabled them to broaden the analytical base with routine structural determinations.« less

NOTE: Acceleration of Monte Carlo-based scatter compensation for cardiac SPECT

NASA Astrophysics Data System (ADS)

Sohlberg, A.; Watabe, H.; Iida, H.

2008-07-01

Single proton emission computed tomography (SPECT) images are degraded by photon scatter making scatter compensation essential for accurate reconstruction. Reconstruction-based scatter compensation with Monte Carlo (MC) modelling of scatter shows promise for accurate scatter correction, but it is normally hampered by long computation times. The aim of this work was to accelerate the MC-based scatter compensation using coarse grid and intermittent scatter modelling. The acceleration methods were compared to un-accelerated implementation using MC-simulated projection data of the mathematical cardiac torso (MCAT) phantom modelling 99mTc uptake and clinical myocardial perfusion studies. The results showed that when combined the acceleration methods reduced the reconstruction time for 10 ordered subset expectation maximization (OS-EM) iterations from 56 to 11 min without a significant reduction in image quality indicating that the coarse grid and intermittent scatter modelling are suitable for MC-based scatter compensation in cardiac SPECT.

Non-MTC gait cycles: An adaptive toe trajectory control strategy in older adults.

PubMed

Santhiranayagam, Braveena K; Sparrow, W A; Lai, Daniel T H; Begg, Rezaul K

2017-03-01

Minimum-toe-clearance (MTC) above the walking surface is a critical representation of toe-trajectory control due to its association with tripping risk. Not all gait cycles exhibit a clearly defined MTC within the swing phase but there have been few previous accounts of the biomechanical characteristics of non-MTC gait cycles. The present report investigated the within-subject non-MTC gait cycle characteristics of 15 older adults (mean 73.1 years) and 15 young controls (mean 26.1 years). Participants performed the following tasks on a motorized treadmill: preferred speed walking, dual task walking (carrying a glass of water) and a dual-task speed-matched control. Toe position-time coordinates were acquired using a 3 dimensional motion capture system. When MTC was present, toe height at MTC (MTC height ) was extracted. The proportion of non-MTC gait cycles was computed for the age groups and individuals. For non-MTC gait cycles an 'indicative' toe height at the individual's average swing phase time (MTC time ) for observed MTC cycles was averaged across multiple non-MTC gait cycles. In preferred-speed walking Young demonstrated 2.9% non-MTC gait cycles and Older 18.7%. In constrained walking conditions both groups increased non-MTC gait cycles and some older adults revealed over 90%, confirming non-MTC gait cycles as an ageing-related phenomenon in lower limb trajectory control. For all participants median indicative toe-height on non-MTC gait cycles was greater than median MTC height . This result suggests that eliminating the biomechanically hazardous MTC event by adopting more of the higher-clearance non-MTC gait cycles, is adaptive in reducing the likelihood of toe-ground contact. Copyright © 2017 Elsevier B.V. All rights reserved.

Current Status of Nuclear Medicine Practice in the Middle East.

PubMed

Paez, Diana; Becic, Tarik; Bhonsle, Uday; Jalilian, Amir R; Nuñez-Miller, Rodolfo; Osso, Joao Alberto

2016-07-01

The practice of nuclear medicine (NM) in the Middle East region has experienced an important growth in the last 2 decades and has become crucial in providing healthcare to the region's population of about 395 million people. Even though there are some countries in which the services provided are limited to basic coverage of studies with (99m)Tc and (131)I, most have well-established practices covering most of the available studies in this medical specialty; this is the case in for example, Iran, Israel, Kuwait, Saudi Arabia, and Turkey. According to data provided by the NM professionals in the 17 countries included in the present publication, which was collected by the International Atomic Energy Agency in 2015, the total number of gamma cameras in the region is 910 with an average of 2.3 gamma cameras per million inhabitants. Out of these, 107 cameras, or 12%, are SPECT/CT cameras. There are 194 operating PET/CT scanners, translating to one PET/CT scanner for 2.04 million people on average. The availability of PET/CT scanners in relation to population is the highest in Lebanon and Kuwait, with 2.2 and 1.7 scanners per million people, respectively. There is a total of 628 NM centers in the 17 countries, whereas most NM centers belong to the public healthcare system and in most of the countries are widely spread and not confined exclusively to capital cities. As for the radionuclide therapies, (131)I is used regularly in diagnostic workup as well as in therapeutic applications in all the countries included in this analysis. Only five countries have the capability of assembling (99)Mo-(99m)Tc generators (Egypt, Iran, Saudi Arabia, Israel, and Turkey), and cold kits are produced in several countries. Although there are no capabilities in the region to produce (99)Mo from nuclear reactors, a total of 46 cyclotrons are operated for production of PET radionuclides. The most widely used PET tracer in the region is (18)F-FDG followed by (18)F-NaF; concomitantly, the availability of (68)Ge-(68)Ga generators is increasing and studies involving prostate-specific membrane antigen or DOTA-chelated peptides or both are performed in at least seven countries. Although therapeutic radionuclide agents are mostly imported from outside the region, this does not limit the availability of therapies with (90)Y, (153)Sm, (177)Lu, (131)I, (188)Re, and (89)Sr. Nevertheless, therapies based on alpha particle emitters are still largely not available in the region and are currently only available in Israel and Turkey. Regarding human resources, according to the data provided there are 1157 NM physicians, 1953 technologists, 586 medical physicists, and 173 radiopharmacists or radiochemists in the region. Approximately half of all available human resources are accounted for by Turkey. The region has great potential for expanding the applications of NM; this becomes especially important in view of the high prevalence of non-communicable diseases. Further increasing awareness of the clinical applications of NM in healthcare and strengthening technical and human capacities including the establishment of training programs for all professionals and disciplines in the field are recognized as key components in advancing the practice of NM in the Middle East. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

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

Grimes, Joshua, E-mail: grimes.joshua@mayo.edu; Celler, Anna

2014-09-15

Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming themore » same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.« less

(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.

(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.

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

PubMed

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

2005-04-01

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

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

Biarsenical labeling of vesicular stomatitis virus encoding tetracysteine-tagged m protein allows dynamic imaging of m protein and virus uncoating in infected cells.

PubMed

Das, Subash C; Panda, Debasis; Nayak, Debasis; Pattnaik, Asit K

2009-03-01

A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) in place of P and a fusion matrix protein (monomeric red fluorescent protein fused in frame at the carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type (wt) M protein in its normal location, was recovered, but the MmRFP was not incorporated into the virions. Subsequently, we generated recombinant viruses (VSV-PeGFP-DeltaM-Mtc and VSV-DeltaM-Mtc) encoding M protein with a carboxy-terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant viruses incorporated Mtc at levels similar to M in wt VSV, demonstrating recovery of infectious rhabdoviruses encoding and incorporating a tagged M protein. Virions released from cells infected with VSV-PeGFP-DeltaM-Mtc and labeled with the biarsenical red dye (ReAsH) were dually fluorescent, fluorescing green due to incorporation of PeGFP in the nucleocapsids and red due to incorporation of ReAsH-labeled Mtc in the viral envelope. Transport and subsequent association of M protein with the plasma membrane were shown to be independent of microtubules. Sequential labeling of VSV-DeltaM-Mtc-infected cells with the biarsenical dyes ReAsH and FlAsH (green) revealed that newly synthesized M protein reaches the plasma membrane in less than 30 min and continues to accumulate there for up to 2 1/2 hours. Using dually fluorescent VSV, we determined that following adsorption at the plasma membrane, the time taken by one-half of the virus particles to enter cells and to uncoat their nucleocapsids in the cytoplasm is approximately 28 min.

Evaluation of (99m)Tc-HYNIC-TMTP1 as a tumor-homing imaging agent targeting metastasis with SPECT.

PubMed

Li, Fei; Cheng, Teng; Dong, Qingjian; Wei, Rui; Zhang, Zhenzhong; Luo, Danfeng; Ma, Xiangyi; Wang, Shixuan; Gao, Qinglei; Ma, Ding; Zhu, Xiaohua; Xi, Ling

2015-03-01

TMTP1 (NVVRQ) is a novel tumor-homing peptide, which specifically targets tumor metastases, even at the early stage of occult metastasis foci. Fusing TMTP1 to therapeutic peptides or proteins can increase its anti-cancer efficacy both in vivo and in vitro. Here, we labeled TMTP1 with (99m)Tc to evaluate its targeting properties in an ovarian cancer xenograft tumor mouse model and a gastric cancer xenograft mouse model. The invasion ability of SKOV3 and highly metastatic SKOV3.ip cell lines were performed by the Transwell Invasion Assays, and then Rhodamine-TMTP1 was used to detect its affinity to these two cells. Using the co-ligand ethylenediamine-N, N'-diacetic acid (EDDA) and the bifunctional chelator 6-hydrazinonicotinic acid (HYNIC), the TMTP1 peptide was labeled with (99m)Tc. A cell-binding assay was performed by incubating cancer cells with (99m)Tc-HYNIC-TMTP1 with or without an excess dose of cold HYNIC-TMTP1. To evaluate the probe in vivo, nude mice bearing SKOV3, SKOV3.ip and MNK-45 tumor cells were established and subjected to SPECT imaging after injection with (99m)Tc-HYNIC-TMTP1. Ex vivo γ-counting of dissected tissues from the mice was used to evaluate its biodistribution. (99m)Tc-HYNIC-TMTP1 was successfully synthesized. The radiotracer also exhibited high hydrophilicity and excellent stability in vitro and in vivo. It has strong affinity to highly metastatic cancer cell lines but not to poorly metastatic cell lines. After mice were injected with (99m)Tc-HYNIC-TMTP1, non-invasive SPECT imaging detected SKOV3.ip and MNK-45 xenograft tumors but not SKOV3 xenograft tumors. This result can be inhibited by excess HYNIC-TMTP1. The uptake of (99m)Tc-HYNIC-TMTP1 in SKOV3.ip xenograft tumors was 0.182±0.017% ID/g at 2h p.i. with high renal uptake (74.32±15.05% ID/g at 2h p.i.). (99m)Tc-HYNIC-TMTP1 biodistribution and SPECT imaging demonstrated its ability to target highly metastatic tumors. Therefore, metastasis can be non-invasively investigated by SPECT imaging using (99m)Tc-HYNIC-TMTP1. Meanwhile, this radiotracer has some shortages in the low % ID/g of tumors and high accumulation in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

Simple-random-sampling-based multiclass text classification algorithm.

PubMed

Liu, Wuying; Wang, Lin; Yi, Mianzhu

2014-01-01

Multiclass text classification (MTC) is a challenging issue and the corresponding MTC algorithms can be used in many applications. The space-time overhead of the algorithms must be concerned about the era of big data. Through the investigation of the token frequency distribution in a Chinese web document collection, this paper reexamines the power law and proposes a simple-random-sampling-based MTC (SRSMTC) algorithm. Supported by a token level memory to store labeled documents, the SRSMTC algorithm uses a text retrieval approach to solve text classification problems. The experimental results on the TanCorp data set show that SRSMTC algorithm can achieve the state-of-the-art performance at greatly reduced space-time requirements.

Assessment of Using 99Mo and 99mTc Isotopes in Kuwait Medical Sector.

PubMed

Ali, Naser

2016-04-01

The Ministry of Health (MOH) in the state of Kuwait currently depends on importing the radioisotope molybdenum (Mo) in its isotopic form (Mo) to fulfill its demands. The present study was conducted on all nuclear medicine departments in the state of Kuwait. Daily, weekly, and monthly data were analyzed to statistically determine the current and future demands for the isotope Tc. This analysis was performed by collecting and analyzing data on MOH consumption of Tc for different diagnostic applications. The overall results indicate a partial decrease of 1.012% in the overall total demand for Tc up to the year 2018 for the state of Kuwait.

The cleaning and disinfection by heat of bedpans in automatic and semi-automatic machines.

PubMed Central

Mostafa, A. B.; Chackett, K. F.

1976-01-01

This work is concerned with the cleaning and disinfection by heat of stainless-steel and polypropylene bedpans, which had been soiled with either a biological contaminant, human serum albumin (HSA) labelled with technetium-99m 99m(Tc), or a bacteriological contaminant, streptococcus faecalis mixed with Tc-labelled HSA. Results of cleaning and disinfection achieved with a Test Machine and those achieved by procedures adopted in eight different wards of a general hospital are reported. Bedpan washers installed in wards were found to be less efficient than the Test Machine, at least partly because of inadequate maintenance. Stainless-steel and polypropylene bedpans gave essentially the same results. PMID:6591

Cell-mediated lysis of lipid vesicles containing eye muscle protein: Implications regarding pathogenesis of Graves ophthalmopathy*

PubMed Central

Kriss, Joseph P.; Mehdi, S. Qasim

1979-01-01

We prepared artificial vesicles that are lysed upon cell-mediated immunological attack by human lymphocytes. These vesicles are made from a mixture of dimyristoyl lecithin, dipalmitoyl lecithin, and cholesterol, have eye muscle membrane protein (EMP) inserted into the bilayer wall, and contain intravesicular 99mTc marker. Injury to the vesicular membrane was assessed by measurement of 99mTc release. Thyroglobulin (Tg) and Tg-anti-Tg complex (TgA) bind to EMP-vesicles to an extent equal to or greater than to native eye muscle membranes in vitro; this binding requires the presence of normal human IgG. The role of Tg, TgA, IgG, and peripheral blood lymphocytes in altering membrane permeability was analyzed. Incubation of vesicles for up to 3 hr alone, with added IgG alone, or with further addition of Tg or TgA did not result in 99mTc release. Addition of lymphocytes from normal donors to the above four preparations showed release in the presence of TgA. Lymphocytes from each of eight patients with Graves ophthalmopathy caused release not only in the presence of TgA, but also in the presence of Tg. Separation of a patient's lymphocytes into high- and low-affinity rosette-formers (T and K cells, respectively) showed that cell-mediated vesicle lysis in the presence of TgA was greater with K cells than with T cells, while vesicle lysis in the presence of Tg was greater with T cells than with K cells. Vesicles made with inserted Tg but lacking EMP were not lysed by such T cells. Lymphocytes failed to induce permeability changes in vesicles containing other inserted proteins obtained from human nonextraocular muscle, liver, spleen, or adrenal, even if Tg or TgA were present. The results support the concept that muscle cell damage in Graves ophthalmopathy is immunological, cell-mediated, and of two types: (i) K lymphocytes reacting to immune complex, TgA, on the eye muscle cell surface (i.e., antibody-dependent cytotoxicity) and (ii) sensitized T lymphocytes reacting to Tg on the eye muscle cell surface. An antigenic role for EMP is possible, but has not been unequivocally proven. PMID:88053

Minimum toe clearance events in divided attention treadmill walking in older and young adults: a cross-sectional study.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Sparrow, W A; Begg, Rezaul K

2015-07-12

Falls in older adults during walking frequently occur while performing a concurrent task; that is, dividing attention to respond to other demands in the environment. A particularly hazardous fall-related event is tripping due to toe-ground contact during the swing phase of the gait cycle. The aim of this experiment was to determine the effects of divided attention on tripping risk by investigating the gait cycle event Minimum Toe Clearance (MTC). Fifteen older adults (mean 73.1 years) and 15 young controls (mean 26.1 years) performed three walking tasks on motorized treadmill: (i) at preferred walking speed (preferred walking), (ii) while carrying a glass of water at a comfortable walking speed (dual task walking), and (iii) speed-matched control walking without the glass of water (control walking). Position-time coordinates of the toe were acquired using a 3 dimensional motion capture system (Optotrak NDI, Canada). When MTC was present, toe height at MTC (MTC_Height) and MTC timing (MTC_Time) were calculated. The proportion of non-MTC gait cycles was computed and for non-MTC gait cycles, toe-height was extracted at the mean MTC_Time. Both groups maintained mean MTC_Height across all three conditions. Despite greater MTC_Height SD in preferred gait, the older group reduced their variability to match the young group in dual task walking. Compared to preferred speed walking, both groups attained MTC earlier in dual task and control conditions. The older group's MTC_Time SD was greater across all conditions; in dual task walking, however, they approximated the young group's SD. Non-MTC gait cycles were more frequent in the older group across walking conditions (for example, in preferred walking: young - 2.9 %; older - 18.7 %). In response to increased attention demands older adults preserve MTC_Height but exercise greater control of the critical MTC event by reducing variability in both MTC_Height and MTC_Time. A further adaptive locomotor control strategy to reduce the likelihood of toe-ground contacts is to attain higher mid-swing clearance by eliminating the MTC event, i.e. demonstrating non-MTC gaits cycles.

Microbial impacts on 99mTc migration through sandstone under highly alkaline conditions relevant to radioactive waste disposal.

PubMed

Smith, Sarah L; Boothman, Christopher; Williams, Heather A; Ellis, Beverly L; Wragg, Joanna; West, Julia M; Lloyd, Jonathan R

2017-01-01

Geological disposal of intermediate level radioactive waste in the UK is planned to involve the use of cementitious materials, facilitating the formation of an alkali-disturbed zone within the host rock. The biogeochemical processes that will occur in this environment, and the extent to which they will impact on radionuclide migration, are currently poorly understood. This study investigates the impact of biogeochemical processes on the mobility of the radionuclide technetium, in column experiments designed to be representative of aspects of the alkali-disturbed zone. Results indicate that microbial processes were capable of inhibiting 99m Tc migration through columns, and X-ray radiography demonstrated that extensive physical changes had occurred to the material within columns where microbiological activity had been stimulated. The utilisation of organic acids under highly alkaline conditions, generating H 2 and CO 2 , may represent a mechanism by which microbial processes may alter the hydraulic conductivity of a geological environment. Column sediments were dominated by obligately alkaliphilic H 2 -oxidising bacteria, suggesting that the enrichment of these bacteria may have occurred as a result of H 2 generation during organic acid metabolism. The results from these experiments show that microorganisms are able to carry out a number of processes under highly alkaline conditions that could potentially impact on the properties of the host rock surrounding a geological disposal facility for intermediate level radioactive waste. Copyright © 2016. Published by Elsevier B.V.

Noise suppressed partial volume correction for cardiac SPECT/CT

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

Chan, Chung; Liu, Chi, E-mail: chi.liu@yale.edu

Purpose: Partial volume correction (PVC) methods typically improve quantification at the expense of increased image noise and reduced reproducibility. In this study, the authors developed a novel voxel-based PVC method that incorporates anatomical knowledge to improve quantification while suppressing noise for cardiac SPECT/CT imaging. Methods: In the proposed method, the SPECT images were first reconstructed using anatomical-based maximum a posteriori (AMAP) with Bowsher’s prior to penalize noise while preserving boundaries. A sequential voxel-by-voxel PVC approach (Yang’s method) was then applied on the AMAP reconstruction using a template response. This template response was obtained by forward projecting a template derived frommore » a contrast-enhanced CT image, and then reconstructed using AMAP to model the partial volume effects (PVEs) introduced by both the system resolution and the smoothing applied during reconstruction. To evaluate the proposed noise suppressed PVC (NS-PVC), the authors first simulated two types of cardiac SPECT studies: a {sup 99m}Tc-tetrofosmin myocardial perfusion scan and a {sup 99m}Tc-labeled red blood cell (RBC) scan on a dedicated cardiac multiple pinhole SPECT/CT at both high and low count levels. The authors then applied the proposed method on a canine equilibrium blood pool study following injection with {sup 99m}Tc-RBCs at different count levels by rebinning the list-mode data into shorter acquisitions. The proposed method was compared to MLEM reconstruction without PVC, two conventional PVC methods, including Yang’s method and multitarget correction (MTC) applied on the MLEM reconstruction, and AMAP reconstruction without PVC. Results: The results showed that the Yang’s method improved quantification, however, yielded increased noise and reduced reproducibility in the regions with higher activity. MTC corrected for PVE on high count data with amplified noise, although yielded the worst performance among all the methods tested on low-count data. AMAP effectively suppressed noise and reduced the spill-in effect in the low activity regions. However it was unable to reduce the spill-out effect in high activity regions. NS-PVC yielded superior performance in terms of both quantitative assessment and visual image quality while improving reproducibility. Conclusions: The results suggest that NS-PVC may be a promising PVC algorithm for application in low-dose protocols, and in gated and dynamic cardiac studies with low counts.« less

Comparison of 133 xenon ventilation equilibrium scan (XV) and 99m technetium transmission (TT) scan for use in regional lung analysis by 2D gamma scintigraphy in healthy and cystic fibrosis lungs.

PubMed

Zeman, Kirby L; Wu, Jihong; Donaldson, Scott H; Bennett, William D

2013-04-01

Quantification of particle deposition in the lung by gamma scintigraphy requires a reference image for location of regions of interest (ROIs) and normalization to lung thickness. In various laboratories, the reference image is made by a transmission scan ((57)Co or (99m)Tc) or gas ventilation scan ((133)Xe or (81)Kr). There has not been a direct comparison of measures from the two methods. We compared (99m)Tc transmission scans to (133)Xe equilibrium ventilation scans as reference images for 38 healthy subjects and 14 cystic fibrosis (CF) patients for their effects on measures of regional particle deposition: the central-to-peripheral ratio of lung counts (C/P); and ROI area versus forced vital capacity. Whole right lung ROI was based on either an isocontour threshold of three times the soft tissue transmission (TT) or a threshold of 20% of peak xenon ventilation counts (XV). We used a central ROI drawn to 50% of height and of width of the whole right lung ROI and placed along the left lung margin and centered vertically. In general, the correlation of normalized C/P (nC/P) between the two methods was strong. However, the value of nC/P was significantly smaller for the XV method than the TT method. Regression equations for the relationship of nC/P between the two methods were, for healthy subjects, y=0.75x+0.61, R(2)=0.64 using rectangular ROIs and y=0.76x+0.45, R(2)=0.66 using isocontour ROIs; and for CF patients, y=0.94x+0.46, R(2)=0.43 and y=0.85x+0.42, R(2)=0.41, respectively. (1) A transmission scan with an isocontour outline in combination with a rectangular central region to define the lung borders may be more useful than a ventilation scan. (2) Close correlation of nC/Ps measured by transmission or gas ventilation should allow confident comparison of values determined by the two methods.

Development of a Hampton University Program for Novel Breast Cancer Imaging and Therapy Research

DTIC Science & Technology

2015-06-01

student ( Nanda Karthik) involved…. Should be able to give you some text!]. Aim 2 Develop and test a practical method for application of a magnetic field ...a Department of Energy (DOE) nuclear physics research facility operated by Jefferson Science Associates LLC. Jefferson Lab resources for this...minimally affected by breast density because of the higher energy photons of 99mTc. In a recent study that included patients who had inconclusive

Gallium scanning in cerebral and cranial infections. [/sup 67/Ga, /sup 99m/Tc tracer techniques

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

Waxman, A.D.; Siemsen, J.K.

1976-08-01

Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, while meningitis or cerebritis gave inconsistent results.

Preparation of ion-activated in situ gel systems of scopolamine hydrobromide and evaluation of its antimotion sickness efficacy.

PubMed

Cao, Shi-lei; Zhang, Qi-zhi; Jiang, Xin-guo

2007-04-01

To develop a novel, in situ gel system for nasal delivery of scopolamine hydrobromide (SCOP) and study its efficacy on motion sickness. SCOP in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of viscosity, in vitro release, and nasal ciliotoxicity. Single photon emission computing tomography technique was used to evaluate the nasal residence time of gel containing (99m)Tc tracer. The antimotion sickness efficacy produced by the in situ gel formulation was investigated in rats and compared with those achieved after subcutaneous and oral administration. The viscosity of the gellan gum formulations either in solution or in gel increased with increasing concentrations of gellan gum. Its release in vitro was moderate in artificial nasal fluid. The micrographic results showed that in situ gels were safe, without nasal ciliotoxicity. In comparison with phosphate buffer saline, a prolonged radioactivity of (99m)Tc in the rabbit nasal cavity was observed after administration of the gellan gum formulation. Intranasal SCOP in situ gel at a dose of 100 microg/kg decreased symptoms of motion sickness significantly in comparison with subcutaneous and oral administration (P<0.01). SCOP nasal in situ gel is a safe and promising therapeutic alternative to existing medications for motion sickness.

Small vessel hematocrit in ischemic myocardium

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

Gumm, D.C.; Cooper, S.M.; Marcus, M.L.

1986-03-01

As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement ofmore » retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.« less

SU-E-T-507: Internal Dosimetry in Nuclear Medicine Using GATE and XCAT Phantom: A Simulation Study

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

Fallahpoor, M; Abbasi, M; Sen, A

Purpose Monte Carlo simulations are routinely used for internal dosimetry studies. These studies are conducted with humanoid phantoms such as the XCAT phantom. In this abstract we present the absorbed doses for various pairs of source and target organs using three common radiotracers in nuclear medicine. Methods The GATE software package is used for the Monte Carlo simulations. A typical female XCAT phantom is used as the input. Three radiotracers 153Sm, 131I and 99mTc are studied. The Specific Absorbed Fraction (SAF) for gamma rays (99mTc, 153Sm and 131I) and Specific Fraction (SF) for beta particles (153Sm and 131I) are calculatedmore » for all 100 pairs of source target organs including brain, liver, lung, pancreas, kidney, adrenal, spleen, rib bone, bladder and ovaries. Results The source organs themselves gain the highest absorbed dose as compared to other organs. The dose is found to be inversely proportional to distance from the source organ. In SAF results of 153Sm, when the source organ is lung, the rib bone, gain 0.0730 (Kg-1) that is more than lung itself. Conclusion The absorbed dose for various organs was studied in terms of SAF and SF. Such studies hold importance for future therapeutic procedures and optimization of induced radiotracer.« less

The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae.

PubMed

Tsai, Chung-Fen; Yip, Ping-Keung; Chen, Shao-Yuan; Lin, Jen-Cheng; Yeh, Zai-Ting; Kung, Lan-Yu; Wang, Cheng-Yi; Fan, Yu-Ming

2014-04-01

Acute carbon monoxide (CO) poisoning poses a significant threat to the central nervous system. It can cause brain injury and diverse neurological deficits including persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). The study aimed to investigate the long-term impacts of acute CO poisoning on brain perfusion and neurological function, and to explore potential differences between PNS and DNS patients. We evaluated brain perfusion using (99m)Tc ethyl cysteinate (ECD) brain single photon emission computed tomography (SPECT) and assessed clinical neurological symptoms and signs one month following acute poisoning. For DNS patients, ECD SPECT and clinical evaluation were performed when their delayed symptoms appeared. All patients had follow-up SPECT imaging, along with clinical assessments six months following poisoning. 12 PNS and 12 DNS patients were recruited between 2007 and 2010. Clinically, the main characteristic presentations were cognitive decline, emotional instability, and gait disturbance. SPECT imaging demonstrated consistent frontal hypoperfusion of varying severities in all patients, which decreased in severity at follow-up imaging. DNS patients usually had more severe symptoms and perfusion defects, along with worse clinical outcomes than the PNS group. These results suggest that acute CO poisoning might lead to long term brain injuries and neurological sequelae, particularly in DNS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional imaging of estrogen receptors with radiolabeled-GAP-EDL in rabbit endometriosis model.

PubMed

Takahashi, Nobukazu; Yang, David J; Kurihara, Hiroaki; Borne, Agatha; Kohanim, Saady; Oh, Chang-Sok; Mawlawi, Osama; Kim, E Edmund

2007-09-01

Endometriosis is a common women's health problem. Animal models provide an invaluable tool to study the natural history of endometriosis. We previously have reported that (99m)Tc-labeled glutamate peptide-estradiol ((99m)Tc-GAP-EDL) is a useful agent for imaging functional estrogen receptor (ER) via an ER-mediated process. This study was to evaluate the feasibility of using radiolabeled GAP-EDL to image ER-positive (ER +) endometriosis in nonprimate animal models. 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of (99m)Tc and (68)Ga-GAP-EDL inhibition with cold estrone were conducted in 13,762 rat mammary tumor cells. To create a rabbit model with endometriosis, part of uterine tissue was dissected and grafted in the peritoneal wall. Eight weeks after surgery, scintigraphic images were obtained after intravenous injection of (99m)Tc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5-2.0 hours, and (68)Ga-GAP-EDL at 45 minutes. We also performed (68)Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination. In vitro uptake study of (99m)Tc- and (68)Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of (68)Ga-GAP-EDL in 13,762 cells was inhibited with cold estrone in a dose-dependent manner. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Necropsy was performed at 2.5 hours after injection time. Four follicular endometrial lesions in eight implanted endometrial tissues were detected, and all lesions could be detected by (99m)Tc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of (99m)Tc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that (99m)Tc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, (68)Ga-GAP-EDL accumulation in the endometrial grafts could not be visualized, and endometrial tissue-to-normal tissue count ratios were statistically higher in a nonblocked image than that in the blocked image. Endometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis.

3D dosimetry estimation for selective internal radiation therapy (SIRT) using SPECT/CT images: a phantom study

NASA Astrophysics Data System (ADS)

Debebe, Senait A.; Franquiz, Juan; McGoron, Anthony J.

2015-03-01

Selective Internal Radiation Therapy (SIRT) is a common way to treat liver cancer that cannot be treated surgically. SIRT involves administration of Yttrium - 90 (90Y) microspheres via the hepatic artery after a diagnostic procedure using 99mTechnetium (Tc)-macroaggregated albumin (MAA) to detect extrahepatic shunting to the lung or the gastrointestinal tract. Accurate quantification of radionuclide administered to patients and radiation dose absorbed by different organs is of importance in SIRT. Accurate dosimetry for SIRT allows optimization of dose delivery to the target tumor and may allow for the ability to assess the efficacy of the treatment. In this study, we proposed a method that can efficiently estimate radiation absorbed dose from 90Y bremsstrahlung SPECT/CT images of liver and the surrounding organs. Bremsstrahlung radiation from 90Y was simulated using the Compton window of 99mTc (78keV at 57%). 99mTc images acquired at the photopeak energy window were used as a standard to examine the accuracy of dosimetry prediction by the simulated bremsstrahlung images. A Liqui-Phil abdominal phantom with liver, stomach and two tumor inserts was imaged using a Philips SPECT/CT scanner. The Dose Point Kernel convolution method was used to find the radiation absorbed dose at a voxel level for a three dimensional dose distribution. This method will allow for a complete estimate of the distribution of radiation absorbed dose by tumors, liver, stomach and other surrounding organs at the voxel level. The method provides a quantitative predictive method for SIRT treatment outcome and administered dose response for patients who undergo the treatment.

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

Portal Vein Embolization with Radiolabeled Polyvinyl Alcohol Particles in a Swine Model: Hepatic Distribution and Implications for Pancreatic Islet Cell Transplantation

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

Owen, Richard J., E-mail: drrichardowen@tbwifi.c; Mercer, John R.; Al-Saif, Faisal

2009-05-15

The distribution of radiolabeled polyvinyl alcohol microspheres (PVAMs) when infused into the portal vein of domestic swine was investigated, with the purpose of assessing implications for pancreatic islet cell transplantation. PVAMs measuring 100-300 {mu}m (Contour SE) and labeled with {sup 99m}Tc were infused into the main portal vein of 12 swine, with intermittent portal venous pressure measurements. The infusion catheter was introduced antegradely via direct or indirect cannulation of the portal vein. The liver was subsequently divided into anatomical segments. Radioactivity (decay corrected) was measured for {sup 99m}Tc microsphere synthesis, dose preparation, gross organ activities, tissue samples, and blood. Particulatemore » labeling, catheter positioning, and infusion were successful in all cases. The number of particles used was (185,000 {+-} 24,000) with a volume of 1 ml. Mean portal pressure at 5 min was significantly higher than baseline, but without a significant difference at 15 min. Extrahepatic tissue and serum radioactivity was negligible. A significant difference in number of radioactive particles per gram was detected between segments 6/7 and segments 5/8. Intrasegmental activity was analyzed, and for segments 2/3 a significant difference in the percentage dose per gram across samples was demonstrated (P = 0.001). Effective and stable radiolabeling of PVAMs with {sup 99m}Tc-sulfur colloid was demonstrated. Portal venous infusion of 100- to 300-{mu}m particles showed entrapment in the sinusoidal hepatic system with transient portal pressure elevation. Preferential embolization into the right lateral and posterior segments occurs, suggesting that flow dynamics/catheter tip position plays a role in particle distribution.« less

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.

[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.

Synthesis and characterization of fac-Re(CO)3-aspartic-N-monoacetic acid, a structural analogue of a potential new renal tracer, fac-99mTc(CO)3(ASMA)

PubMed Central

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

2013-01-01

The reaction of an aminopolycarboxylate ligand, aspartic-N-monoacetic acid (ASMA), with [Re(CO)3(H2O)3]+ was examined. The tridentate coordination of ASMA to this ReI tricarbonyl precursor yielded fac-Re(CO)3(ASMA) as a mixture of diastereomers. The chemistry is analogous to that of the TcI tricarbonyl complex, which yields fac-99mTc(CO)3(ASMA) under similar conditions. The formation, structure, and isomerization of fac-Re(CO)3(ASMA) products were characterized by HPLC, 1H NMR spectroscopy, and X-ray crystallography. The two major fac-Re(CO)3(ASMA) diastereomeric products each have a linear ONO coordination mode with two adjacent five-membered chelate rings, but they differ in the endo or exo orientation of the uncoordinated acetate group, in agreement with expectations based on previous studies. Conditions have been identified for the expedient isomerization of fac-Re(CO)3(ASMA) to a mixture consisting primarily of one major product. Because different isomeric species typically have different pharmacokinetic characteristics, these conditions may provide for the practical isolation of a single 99mTc(CO)3(ASMA) species, thus allowing the isolation of the isomer that has optimal imaging and pharmacokinetic characteristics. This information will aid in the design of future 99mTc radiopharmaceuticals. PMID:24273448

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.

A technetium-labeled monoclonal antibody for imaging metastatic melanoma

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

Frytak, S.; Creagan, E.T.; Brown, M.L.

1991-04-01

Twenty patients with histologically proven metastatic melanoma were scanned with a 99mtechnetium ({sup 99}mTc)-labeled melanoma antibody to determine the detection rate of known malignant lesions and to evaluate the antibody's ability to discover occult metastases. Isotope localization in different organs was as follows: liver 100%, bone 100%, subcutaneous lesions 80%, lymph nodes 54%, and lung 33%. Four unsuspected bone lesions and 16 occult subcutaneous lesions were found. False positive lesions were noted in two instances--one benign thyroid adenoma, and one arthritic bone lesion. One patient developed an atypical serum sickness reaction with a rash and arthralgias that responded rapidly tomore » treatment. The {sup 99}mTc antimelanoma antibody is a safe and effective method to detect metastatic melanoma. It has potential use for screening newly diagnosed melanomas that carry an increased risk of recurrence.« less

Osteomesopyknosis: report of a new case with bone histology.

PubMed

Hardouin, P; Flautre, B; Sutter, B; Leclet, H; Grardel, B; Fauquert, P

1994-01-01

A new case of osteomesopyknosis, a rare autosomal dominant axial osteosclerosis is reported, with 4 affected members of the same family. Biochemical investigations, bone mineral content (BMC) measurement, 99mTc HMDP bone scan and microscopy of iliac crest bone and femoral head have been performed on 1 subject. A marked increase of BMC was found, without abnormality of biochemical data. Microscopy of bone showed an increase of trabecular thickness, and a low rate of bone turnover. No abnormality of mineralization was found on microradiographs.

[Parasternal lymphoscintigraphy in planning the radiation therapy of breast cancer].

PubMed

Bykov, S A; Mironov, E E; Zhdanova, V I

1990-07-01

Altogether 82 breast cancer patients were investigated to determine a possibility of the use of parasternal lymphoscintigraphy with colloid finely divided radiopharmaceuticals 99mTc and 198Au to form individual irradiation fields; 43 patients with fibroadenomatosis were taken as controls. Variants of the localization of parasternal lymph nodes were defined, standard and "optimum" (individual) parasternal irradiation field values were compared. 54.9% of the patients were shown to be in need of correction by increasing a standard irradiation field (5 cm wide).

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.

Somatostatin Receptor SPECT/CT using 99mTc Labeled HYNIC-TOC Aids in Diagnosis of Primary Optic Nerve Sheath Meningioma.

PubMed

Chandra, Piyush; Purandare, Nilendu; Shah, Sneha; Agrawal, Archi; Rangarajan, Venkatesh

2017-01-01

Primary optic nerve sheath meningiomas (ONSM) are rare, benign and slow growing tumor involving the intra-orbital/intra-canalicular segment of the optic nerve. Untreated, they can potentially lead to visual deterioration. Magnetic resonance (MR) is the gold standard imaging modality for diagnosing the entity. Often, a clinical dilemma exists to narrow the differential diagnosis of an enhancing intra-orbital mass on MR. Molecular imaging provides a high degree of precision in diagnosing meningioma in view of relatively high levels of somatostatin receptor expression by these tumors. The following case demonstrates the potential clinical utility of somatostatin receptor SPECT using 99m Tc- labeled HYNIC-TOC in clinical diagnosis of ONSM.

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

Bronn, L.J.; Paquelet, J.R.; Tetalman, M.R.

Imaging of the bone marrow by radionuclide scanning was performed using colloids, which are phagocytized by the reticuloendothelial cells of the marrow, or radioiron, which is incorporated into reticulocytes. The use of the former radiopharmaceutical is based on the assumption, generally valid except in aplastic states or after irradiation, that the distribution of hematopoietic and reticuloendothelial tissue in the marrow is similar. Regardless of the method used, active adult marrow is normally distributed only in the axial skeleton and proximal humeri and femurs. Marrow imaging has been used in the evaluation of myeloproliferative disorders, leukemia, lymphoma, aplastic states, malignancy metastaticmore » to marrow, and hemolytic anemia. We report a case of thalassemia major in which the diagnosis of intrathoracic extramedullary hematopoiesis was confirmed with the /sup 99m/Tc sulfur colloid bone marrow scan.« less

Monte Carlo based approach to the LS-NaI 4πβ-γ anticoincidence extrapolation and uncertainty

PubMed Central

Fitzgerald, R.

2016-01-01

The 4πβ-γ anticoincidence method is used for the primary standardization of β−, β+, electron capture (EC), α, and mixed-mode radionuclides. Efficiency extrapolation using one or more γ ray coincidence gates is typically carried out by a low-order polynomial fit. The approach presented here is to use a Geant4-based Monte Carlo simulation of the detector system to analyze the efficiency extrapolation. New code was developed to account for detector resolution, direct γ ray interaction with the PMT, and implementation of experimental β-decay shape factors. The simulation was tuned to 57Co and 60Co data, then tested with 99mTc data, and used in measurements of 18F, 129I, and 124I. The analysis method described here offers a more realistic activity value and uncertainty than those indicated from a least-squares fit alone. PMID:27358944

Assessment of cardiac function using myocardial perfusion imaging technique on SPECT with 99mTc sestamibi

NASA Astrophysics Data System (ADS)

Gani, M. R. A.; Nazir, F.; Pawiro, S. A.; Soejoko, D. S.

2016-03-01

Suspicion on coronary heart disease can be confirmed by observing the function of left ventricle cardiac muscle with Myocardial Perfusion Imaging techniques. The function perfusion itself is indicated by the uptake of radiopharmaceutical tracer. The 31 patients were studied undergoing the MPI examination on Gatot Soebroto Hospital using 99mTc-sestamibi radiopharmaceutical with stress and rest conditions. Stress was stimulated by physical exercise or pharmacological agent. After two hours, the patient did rest condition on the same day. The difference of uptake percentage between stress and rest conditions will be used to determine the malfunction of perfusion due to ischemic or infarct. Degradation of cardiac function was determined based on the image-based assessment of five segments of left ventricle cardiac. As a result, 8 (25.8%) patients had normal myocardial perfusion and 11 (35.5%) patients suspected for having partial ischemia. Total ischemia occurred to 8 (25.8%) patients with reversible and irreversible ischemia and the remaining 4 (12.9%) patients for partial infarct with characteristic the percentage of perfusion ≤50%. It is concluded that MPI technique of image-based assessment on uptake percentage difference between stress and rest conditions can be employed to predict abnormal perfusion as complementary information to diagnose the cardiac function.

High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

PubMed

Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

2012-12-01

Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy to image force responses in living cells.

PubMed

Zhang, Yuejin; Wei, Fuxiang; Poh, Yeh-Chuin; Jia, Qiong; Chen, Junjian; Chen, Junwei; Luo, Junyu; Yao, Wenting; Zhou, Wenwen; Huang, Wei; Yang, Fang; Zhang, Yao; Wang, Ning

2017-07-01

Cells and tissues can undergo a variety of biological and structural changes in response to mechanical forces. Only a few existing techniques are available for quantification of structural changes at high resolution in response to forces applied along different directions. 3D-magnetic twisting cytometry (3D-MTC) is a technique for applying local mechanical stresses to living cells. Here we describe a protocol for interfacing 3D-MTC with confocal fluorescence microscopy. In 3D-MTC, ferromagnetic beads are bound to the cell surface via surface receptors, followed by their magnetization in any desired direction. A magnetic twisting field in a different direction is then applied to generate rotational shear stresses in any desired direction. This protocol describes how to combine magnetic-field-induced mechanical stimulation with confocal fluorescence microscopy and provides an optional extension for super-resolution imaging using stimulated emission depletion (STED) nanoscopy. This technology allows for rapid real-time acquisition of a living cell's mechanical responses to forces via specific receptors and for quantifying structural and biochemical changes in the same cell using confocal fluorescence microscopy or STED. The integrated 3D-MTC-microscopy platform takes ∼20 d to construct, and the experimental procedures require ∼4 d when carried out by a life sciences graduate student.

Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy to image force responses in living cells

PubMed Central

Zhang, Yuejin; Wei, Fuxiang; Poh, Yeh-Chuin; Jia, Qiong; Chen, Junjian; Chen, Junwei; Luo, Junyu; Yao, Wenting; Zhou, Wenwen; Huang, Wei; Yang, Fang; Zhang, Yao; Wang, Ning

2017-01-01

Cells and tissues can undergo a variety of biological and structural changes in response to mechanical forces. Only few existing techniques are available for quantification of structural changes at high resolution in response to forces applied along different directions. Three dimensional-Magnetic Twisting Cytometry (3D-MTC) is a technique for applying local mechanical stresses on living cells. Here we describe a protocol for interfacing 3D-MTC with confocal fluorescence microscopy. In 3D-MTC, ferromagnetic beads are bound to the cell surface via surface receptors followed by their magnetization in any desired direction. A magnetic twisting field in a different direction is then applied to generate rotational shear stresses in any desired direction. This protocol describes how to combine magnetic field-induced mechanical stimulation with confocal fluorescence microscopy and provides an optional extension for super resolution imaging using stimulated emission depletion (STED) nanoscopy. This technology allows for rapid real time acquisition of a living cell’s mechanical responses to forces via specific receptors and for quantifying structural and biochemical changes in the same cell using confocal fluorescence microscopy or STED. The integrated 3D-MTC – microscopy platform takes around 20 days to construct and the experimental procedures require ~4 days when carried out by a life sciences graduate student. PMID:28686583

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

PubMed Central

Brudey, Karine; Driscoll, Jeffrey R; Rigouts, Leen; Prodinger, Wolfgang M; Gori, Andrea; Al-Hajoj, Sahal A; Allix, Caroline; Aristimuño, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T; Fauville-Dufaux, Maryse; Ferdinand, Séverine; de Viedma, Dario Garcia; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M; Guttierez, M Cristina; Hawkey, Peter M; van Helden, Paul D; Kadival, Gurujaj V; Kreiswirth, Barry N; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaïa, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Zeaur; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M Lucia; Rüsch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor G; Singh, Urvashi B; Somoskovi, Akos; Skuce, Robin A; van Soolingen, Dick; Streicher, Elisabeth M; Suffys, Philip N; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Véronique; Victor, Tommie C; Warren, Robin M; Yap, Sook Fan; Zaman, Khadiza; Portaels, Françoise; Rastogi, Nalin; Sola, Christophe

2006-01-01

Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. PMID:16519816

Radioisotope Production for Medical and Physics Applications

NASA Astrophysics Data System (ADS)

Mausner, Leonard

2012-10-01

Radioisotopes are critical to the science and technology base of the US. Discoveries and applications made as a result of the availability of radioisotopes span widely from medicine, biology, physics, chemistry and homeland security. The clinical use of radioisotopes for medical diagnosis is the largest sector of use, with about 16 million procedures a year in the US. The use of ^99Mo/^99mTc generator and ^18F make up the majority, but ^201Tl, ^123I, ^111In, and ^67Ga are also used routinely to perform imaging of organ function. Application of radioisotopes for therapy is dominated by use of ^131I for thyroid malignancies, ^90Y for some solid tumors, and ^89Sr for bone cancer, but production of several more exotic species such as ^225Ac and ^211At are of significant current research interest. In physics ^225Ra is of interest for CP violation studies, and the actinides ^242Am, ^249Bk, and ^254Es are needed as targets for experiments to create superheavy elements. Large amounts of ^252Cf are needed as a fission source for the CARIBU experiment at ANL. The process of radioisotope production is multidisciplinary. Nuclear physics input based on nuclear reaction excitation function data is needed to choose an optimum target/projectile in order to maximize desired isotope production and minimize unwanted byproducts. Mechanical engineering is needed to address issues of target heating, induced mechanical stress and material compatibility of target and claddings. Radiochemists are involved as well since chemical separation to purify the desired final radioisotope product from the bulk target and impurities is also usually necessary. Most neutron rich species are produced at a few government and university reactors. Other radioisotopes are produced in cyclotrons in the commercial sector, university/hospital based facilities, and larger devices at the DOE labs. The landscape of US facilities, the techniques involved, and current supply challenges will be reviewed.

Influence of muscle-tendon complex geometrical parameters on modeling passive stretch behavior with the Discrete Element Method.

PubMed

Roux, A; Laporte, S; Lecompte, J; Gras, L-L; Iordanoff, I

2016-01-25

The muscle-tendon complex (MTC) is a multi-scale, anisotropic, non-homogeneous structure. It is composed of fascicles, gathered together in a conjunctive aponeurosis. Fibers are oriented into the MTC with a pennation angle. Many MTC models use the Finite Element Method (FEM) to simulate the behavior of the MTC as a hyper-viscoelastic material. The Discrete Element Method (DEM) could be adapted to model fibrous materials, such as the MTC. DEM could capture the complex behavior of a material with a simple discretization scheme and help in understanding the influence of the orientation of fibers on the MTC׳s behavior. The aims of this study were to model the MTC in DEM at the macroscopic scale and to obtain the force/displacement curve during a non-destructive passive tensile test. Another aim was to highlight the influence of the geometrical parameters of the MTC on the global mechanical behavior. A geometrical construction of the MTC was done using discrete element linked by springs. Young׳s modulus values of the MTC׳s components were retrieved from the literature to model the microscopic stiffness of each spring. Alignment and re-orientation of all of the muscle׳s fibers with the tensile axis were observed numerically. The hyper-elastic behavior of the MTC was pointed out. The structure׳s effects, added to the geometrical parameters, highlight the MTC׳s mechanical behavior. It is also highlighted by the heterogeneity of the strain of the MTC׳s components. DEM seems to be a promising method to model the hyper-elastic macroscopic behavior of the MTC with simple elastic microscopic elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

SPECT imaging in evaluating extent of malignant external otitis: case report

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

English, R.J.; Tu'Meh, S.S.; Piwnica-Worms, D.

1987-03-01

Otitis externa, a benign inflammatory process of the external auditory canal, is general responsive to local therapy. Some patients however, develop a less controllable disease leading to chondritis and osteomyelitis of the base of the skull. The direct invasive characteristic of the disease has led to the descriptive term malignant external otitis (MEO), more appropriately called necrotizing or invasive external otitis. Malignant external otitis is caused by an aggressive pseudomonas or proteus infection that almost exclusively occurs in elderly diabetic patients. The primary imaging modalities previously used in the diagnosis and evaluation of MEO were standard planar scintigraphic techniques withmore » technetium-99M (/sup 99m/Tc) bone agents and gallium-67 (/sup 67/Ga), and pluridirectional tomography. The advent of high resolution computed tomography (CT) effectively allowed demonstration of the soft tissue extension and bone destruction associated with MEO, but still suffered from the low sensitivity constraints of all radiographic techniques in determining early inflammatory bone involvement. Recent work suggests that scintigraphic detection of MEO with /sup 99m/Tc-MDP and /sup 67/Ga, combined with the cross-sectional resolution of single photon emission computed tomography (SPECT) may be of value in planning treatment of this inflammatory condition.« less

TheatreLink: Wired to Make Plays Together at a Distance

ERIC Educational Resources Information Center

Shookhoff, David

2004-01-01

Now entering its eighth year, TheatreLink, Manhattan Theater Club's Internet-based distance-learning project remains the most exciting and most challenging initiative. MTC's Education Program had existed for seven years (since 1989 to be exact) before it started TheatreLink. During that early period MTC created an array of programs, all of them…

TH-C-17A-02: New Radioluminescence Strategies Based On CRET (Cerenkov Radiation Energy Transfer) for Imaging and Therapy

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

Volotskova, O; Sun, C; Pratx, G

2014-06-15

Purpose: Cerenkov photons are produced when charged particles, emitted from radionuclides, travel through a media with a speed greater than that of the light in the media. Cerenkov radiation is mostly in the UV/Blue region and, thus, readily absorbed by biological tissue. Cerenkov Radiation Energy Transfer (CRET) is a wavelength-shifting phenomenon from blue Cerenkov light to more penetrating red wavelengths. We demonstrate the feasibility of in-depth imaging of CRET light originating from radionuclides realized by down conversion of gold nanoclusters (AuNCs, a novel particle composed of few atoms of gold coated with serum proteins) in vivo. Methods: Bovine Serum Albumin,more » Human Serum Albumin and Transferrin conjugated gold nanoclusters were synthesized, characterized and examined for CRET. Three different clinically used radiotracers: 18F-FDG, 90Y and 99mTc were used. Optical spectrum (440–750 nm) was recorded by sensitive bioluminescence imaging system at physiological temperature. Dose dependence (activity range from 0.5 up to 800uCi) and concentration dependence (0.01 to 1uM) studies were carried out. The compound was also imaged in a xenograft mouse model. Results: Only β+ and β--emitting radionuclides (18F-FDG, 90Y) are capable of CRET; no signal was found in 99mTc (γ-emitter). The emission peak of CRET by AuNCs was found to be ∼700 nm and was ∼3 fold times of background. In vitro studies showed a linear dependency between luminescence intensity and dose and concentration. CRET by gold nanoclusters was observed in xenografted mice injected with 100uCi of 18F-FDG. Conclusion: The unique optical, transport and chemical properties of AuNCs (gold nanoclusters) make them ideal candidates for in-vivo imaging applications. Development of new molecular imaging probes will allow us to achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor imaging and detection.« less

TECHNETIUM RETENTION IN WTP LAW GLASS WITH RECYCLE FLOW-SHEET DM10 MELTER TESTING VSL-12R2640-1 REV 0

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

Abramowitz, Howard; Brandys, Marek; Cecil, Richard

2012-12-11

Melter tests were conducted to determine the retention of technetium and other volatiles in glass while processing simulated Low Activity Waste (LAW) streams through a DM10 melter equipped with a prototypical off-gas system that concentrates and recycles fluid effiuents back to the melter feed. To support these tests, an existing DM10 system installed at Vitreous State Laboratory (VSL) was modified to add the required recycle loop. Based on the Hanford Tank Waste Treatment and Immobilization Plant (WTP) LAW off-gas system design, suitably scaled versions of the Submerged Bed Scrubber (SBS), Wet Electrostatic Precipitator (WESP), and TLP vacuum evaporator were designed,more » built, and installed into the DM10 system. Process modeling was used to support this design effort and to ensure that issues associated with the short half life of the {sup 99m}Tc radioisotope that was used in this work were properly addressed and that the system would be capable of meeting the test objectives. In particular, this required that the overall time constant for the system was sufficiently short that a reasonable approach to steady state could be achieved before the {sup 99m}Tc activity dropped below the analytical limits of detection. The conceptual design, detailed design, flow sheet development, process model development, Piping and Instrumentation Diagram (P&ID) development, control system design, software design and development, system fabrication, installation, procedure development, operator training, and Test Plan development for the new system were all conducted during this project. The new system was commissioned and subjected to a series of shake-down tests before embarking on the planned test program. Various system performance issues that arose during testing were addressed through a series of modifications in order to improve the performance and reliability of the system. The resulting system provided a robust and reliable platform to address the test objectives.« less

Some short-term effects of changing to lower yield cigarettes

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

Minty, B.D.; Royston, D.; Jones, J.G.

The rate of clearance from the lung of the hydrophilic tracer molecule /sup 99m/Tc DTPA was used to investigate the short-term effects on lung epithelial function when smokers switched to cigarettes with lower yields of tobacco smoke constituents. Two separate studies were performed. In the first study, subjects smoked conventional mid- and low-tar cigarettes. The second study used two specially manufactured cigarettes with similar tar and nicotine yields, but differing carbon monoxide yields. Neither study demonstrated any significant improvement in /sup 99m/Tc DTPA clearance. The yields of carbon monoxide determined under standard machine smoking conditions implied that there would bemore » a 44 percent reduction in exposure to carbon monoxide when subjects switched from smoking conventional mid-tar to low-tar cigarettes. However, measurements of carboxyhemoglobin showed that the smokers compensated for the lower yields and their exposure was reduced by only 11 percent. Similarly, in the second study, the subjects reduced their exposure by 7 percent instead of the expected 44 percent. Urine nicotine/cotinine excretion measurements in this study indicated that there was no complimentary increase in nicotine absorption suggesting the possibility that subjects may be able to regulate their intake of individual components of the cigarette smoke. Thus, the unexpected result from this study was the finding that cigarette smokers could, in some way, regulate their intake of smoke from cigarettes of different composition so as to maintain a constant exposure of smoke constituents.« less

Evaluation of collimation and imaging configuration in scintimammography

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

Tsui, B.M.W.; Frey, E.C.; Wessell, D.E.

1996-12-31

Conventional scintimammography (SM) with {sup 99m}Tc sestamibi has been limited to taking a single lateral view of the breast using a parallel-hole high resolution (LEHR) collimator. The collimator is placed close to the breast for best possible spatial resolution. However, the collimator geometry precludes imaging the breast from other views. We evaluated using a pinhole collimator instead of a LEHR collimator in SM for improved spatial resolution and detection efficiency, and to allow additional imaging views. Results from theoretical calculations indicated that pinhole collimators could be designed with higher spatial resolution and detection efficiency than LEHR when imaging small tomore » medium size breasts. The geometrical shape of the pinhole collimator allows imaging of the breasts from both the lateral and craniocaudal views. The dual-view images allow better determination of the location of the tumors within the breast and improved detection of tumors located in the medial region of the breast. A breast model that simulates the shape and composition of the breast and breast tumors with different sizes and locations was added to an existing 3D mathematical cardiac-torso (MCAT) phantom. A cylindrically shaped phantom with 10 cm diameter and spherical inserts with different sizes and {sup 99m}Tc sestamibi uptakes with respect to the background provide physical models of breast with tumors. Simulation studies using the breast and MCAT phantoms and experimental studies using the cylindrical phantom confirmed the utility of the pinhole collimator in SM for improved breast tumor detection.« less

Dosimetric factors for diagnostic nuclear medicine procedures in a non-reference pregnant phantom.

PubMed

Rafat-Motavalli, Laleh; Miri Hakimabad, Hashem; Hoseinian Azghadi, Elie

2018-05-01

This study was evaluated the impact of using non-reference fetal models on the fetal radiation dose from diagnostic radionuclide administration. The 6 month pregnant phantoms including fetal models at 10th and 90th growth percentiles were constructed at either end of the normal range around the 50th percentile and implemented in the Monte Carlo N-Particle code version MCNPX 2.6. The code have been used then to evaluate the 99mTc S factors of interested target organs as the most common used radionuclide in nuclear medicine procedures. Substantial variations were observed in the S factors between the 10th/90th percentile phantoms from the 50th percentile phantom, with the greatest difference being 38.6 %. When the source organs were in close proximity to, or inside the fetal body, the 99mTc S factors presented strong statistical correlations with fetal body habitus. The trends observed in the S factors and the differences between various percentiles were justified by the source organs' masses, and chord length distributions (CLDs). The results of this study showed that fetal body habitus had a considerable effect on fetal dose (on average up to 8.4%) if constant fetal biokinetic data was considered for all fetal weight percentiles. However, an almost smaller variation on fetal dose (up to 5.3%) was obtained if the available biokinetic data for the reference fetus was scaled by fetal mass. © 2018 IOP Publishing Ltd.

Characterization of a small CsI(Na)-WSF-SiPM gamma camera prototype using 99mTc

NASA Astrophysics Data System (ADS)

Castro, I. F.; Soares, A. J.; Moutinho, L. M.; Ferreira, M. A.; Ferreira, R.; Combo, A.; Muchacho, F.; Veloso, J. F. C. A.

2013-03-01

A small field of view gamma camera is being developed, aiming for applications in scintimammography, sentinel lymph node detection or small animal imaging and research. The proposed wavelength-shifting fibre (WSF) gamma camera consists of two perpendicular sets of WSFs covering both sides of a CsI(Na) crystal, such that the fibres positioned at the bottom of the crystal provide the x coordinate and the ones on top the y coordinate of the gamma photon interaction point. The 2D position is given by highly sensitive photodetectors reading out each WSF and the energy information is provided by PMTs that cover the full detector area. This concept has the advantage of using N+N instead of N × N photodetectors to cover an identical imaging area, and is being applied using for the first time SiPMs. Previous studies carried out with 57Co have proved the feasibility of this concept using SiPM readout. In this work, we present experimental results from true 2D image acquisitions with a 10+10 SiPMs prototype, i.e. 10 × 10 mm2, using a parallel-hole collimator and different samples filled with 99mTc solution. The performance of the small prototype in these conditions is evaluated through the characterization of different gamma camera parameters, such as energy and spatial resolution. Ongoing advances towards a larger prototype of 100+100 SiPMs (10 × 10 cm2) are also presented.

Evaluation of a CdTe semiconductor based compact γ camera for sentinel lymph node imaging.

PubMed

Russo, Paolo; Curion, Assunta S; Mettivier, Giovanni; Esposito, Michela; Aurilio, Michela; Caracò, Corradina; Aloj, Luigi; Lastoria, Secondo

2011-03-01

The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. The room-temperature CdTe pixel detector (1 mm thick) has 256 x 256 square pixels arranged with a 55 microm pitch (sensitive area 14.08 x 14.08 mm2), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. For 99 mTc, at 50 mm distance, a background-subtracted sensitivity of 6.5 x 10(-3) cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3 x 10(-2) cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq 99 mTc and prior localization with standard gamma camera lymphoscintigraphy. The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.

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

PubMed

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

2004-08-01

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

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.

Radioactivity decontamination of materials commonly used as surfaces in general-purpose radioisotope laboratories.

PubMed

Leonardi, Natalia M; Tesán, Fiorella C; Zubillaga, Marcela B; Salgueiro, María J

2014-12-01

In accord with as-low-as-reasonably-achievable and good-manufacturing-practice concepts, the present study evaluated the efficiency of radioactivity decontamination of materials commonly used in laboratory surfaces and whether solvent spills on these materials affect the findings. Four materials were evaluated: stainless steel, a surface comprising one-third acrylic resin and two-thirds natural minerals, an epoxy cover, and vinyl-based multipurpose flooring. Radioactive material was eluted from a (99)Mo/(99m)Tc generator, and samples of the surfaces were control-contaminated with 37 MBq (100 μL) of this eluate. The same procedure was repeated with samples of surfaces previously treated with 4 solvents: methanol, methyl ethyl ketone, acetone, and ethanol. The wet radioactive contamination was allowed to dry and then was removed with cotton swabs soaked in soapy water. The effectiveness of decontamination was defined as the percentage of activity removed per cotton swab, and the efficacy of decontamination was defined as the total percentage of activity removed, which was obtained by summing the percentages of activity in all the swabs required to complete the decontamination. Decontamination using our protocol was most effective and most efficacious for stainless steel and multipurpose flooring. Moreover, treatment with common organic solvents seemed not to affect the decontamination of these surfaces. Decontamination of the other two materials was less efficient and was interfered with by the organic solvents; there was also great variability in the overall results obtained for these other two materials. In expanding our laboratory, it is possible for us to select those surface materials on which our decontamination protocol works best. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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.

Immunohistochemistry of medullary thyroid carcinoma and C-cell hyperplasia by an affinity-purified anti-human calcitonin antiserum.

PubMed

Hayashida, C Y; Alves, V A; Kanamura, C T; Ezabella, M C; Abelin, N M; Nicolau, W; Bisi, H; Toledo, S P

1993-08-15

The diagnosis of medullary thyroid carcinoma (MTC) depends on the calcitonin immunohistochemistry. Familial MTC is associated with C-cell hyperplasia (CCH), whereas sporadic MTC is not. A specific and sensitive calcitonin immunohistochemistry is necessary for the diagnosis of MTC and CCH. An affinity-purified anti-calcitonin antiserum (APxCT) was used for immunohistochemistry of the thyroids of 15 patients with MTC. The thyroids of five patients with familial MTC were studied in detail, with each gland sectioned in 48 areas. Between three and ten independent MTC were found in each thyroid, and CCH was found in all five patients (24.2%, varying from 8.4-56.3% of the 48 areas from each thyroid). MTC and CCH were localized mainly in the middle third and in the central axis of the thyroid lobes. They often were found together in the same area (in a total of 21 areas for the five thyroids sectioned in 48 areas) but ten areas with MTC did not have CCH, and 37 areas with CCH did not have MTC. In ten thyroids partially studied, CCH was indicated in three patients thought to have sporadic MTC. In two thyroids, with follicular and papillary carcinoma, a higher density of C-cells was found around the tumors, but disease was not characterized as CCH. APxCT antiserum increased the immunohistochemical specificity and sensitivity. The distinction of the familial from the sporadic MTC requires a careful and extensive search of CCH. C-cells in high density may be found around follicular cell carcinomas, being a potential source of diagnostic error.

Measuring hepatic functional reserve using T1 mapping of Gd-EOB-DTPA enhanced 3T MR imaging: A preliminary study comparing with 99mTc GSA scintigraphy and signal intensity based parameters.

PubMed

Nakagawa, Masataka; Namimoto, Tomohiro; Shimizu, Kie; Morita, Kosuke; Sakamoto, Fumi; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Shiraishi, Shinya; Yamashita, Yasuyuki

2017-07-01

To determine the utility of liver T1-mapping on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance (MR) imaging for the measurement of liver functional reserve compared with the signal intensity (SI) based parameters, technetium-99m-galactosyl serum albumin ( 99m Tc-GSA) scintigraphy and indocyanine green (ICG) clearance. This retrospective study included 111 patients (Child-Pugh-A 90; -B 21) performed with both Gd-EOB-DTPA enhanced liver MR imaging and 99m Tc-GSA (76 patients with ICG). Receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic performances of T1-relaxation-time parameters [pre-(T1pre) and post-contrast (T1hb) Gd-EOB-DTPA], SI based parameters [relative enhancement (RE), liver-to-muscle-ratio (LMR), liver-to-spleen-ratio (LSR)] and 99m Tc-GSA scintigraphy blood clearance index (HH15)] for Child-Pugh classification. Pearson's correlation was used for comparisons among T1-relaxation-time parameters, SI-based parameters, HH15 and ICG. A significant difference was obtained for Child-Pugh classification with T1hb, ΔT1, all SI based parameters and HH15. T1hb had the highest AUC followed by RE, LMR, LSR, ΔT1, HH15 and T1pre. The correlation coefficients with HH15 were T1pre 0.22, T1hb 0.53, ΔT1 -0.38 of T1 relaxation parameters; RE -0.44, LMR -0.45, LSR -0.43 of SI-based parameters. T1hb was highest for correlation with HH15. The correlation coefficients with ICG were T1pre 0.29, T1hb 0.64, ΔT1 -0.42 of T1 relaxation parameters; RE -0.50, LMR -0.61, LSR -0.58 of SI-based parameters; 0.64 of HH15. Both T1hb and HH15 were highest for correlation with ICG. T1 relaxation time at post-contrast of Gd-EOB-DTPA (T1hb) was strongly correlated with ICG clearance and moderately correlated HH15 with 99m Tc-GSA. T1hb has the potential to provide robust parameter of liver functional reserve. Copyright © 2017 Elsevier B.V. All rights reserved.

The M-T Hook Structure Is Critical for Design of HIV-1 Fusion Inhibitors*

PubMed Central

Chong, Huihui; Yao, Xue; Sun, Jianping; Qiu, Zonglin; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian

2012-01-01

CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. PMID:22879603

LTE-advanced random access mechanism for M2M communication: A review

NASA Astrophysics Data System (ADS)

Mustafa, Rashid; Sarowa, Sandeep; Jaglan, Reena Rathee; Khan, Mohammad Junaid; Agrawal, Sunil

2016-03-01

Machine Type Communications (MTC) enables one or more self-sufficient machines to communicate directly with one another without human interference. MTC applications include smart grid, security, e-Health and intelligent automation system. To support huge numbers of MTC devices, one of the challenging issues is to provide a competent way for numerous access in the network and to minimize network overload. In this article, the different control mechanisms for overload random access are reviewed to avoid congestion caused by random access channel (RACH) of MTC devices. However, past and present wireless technologies have been engineered for Human-to-Human (H2H) communications, in particular, for transmission of voice. Consequently the Long Term Evolution (LTE) -Advanced is expected to play a central role in communicating Machine to Machine (M2M) and are very optimistic about H2H communications. Distinct and unique characteristics of M2M communications create new challenges from those in H2H communications. In this article, we investigate the impact of massive M2M terminals attempting random access to LTE-Advanced all at once. We discuss and review the solutions to alleviate the overload problem by Third Generation Partnership Project (3GPP). As a result, we evaluate and compare these solutions that can effectively eliminate the congestion on the random access channel for M2M communications without affecting H2H communications.

Magnetization transfer contrast-suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T.

PubMed

Xu, Xiang; Yadav, Nirbhay N; Zeng, Haifeng; Jones, Craig K; Zhou, Jinyuan; van Zijl, Peter C M; Xu, Jiadi

2016-01-01

To use the variable delay multipulse (VDMP) chemical exchange saturation transfer (CEST) approach to obtain clean amide proton transfer (APT) and relayed Nuclear Overhauser enhancement (rNOE) CEST images in the human brain by suppressing the conventional magnetization transfer contrast (MTC) and reducing the direct water saturation contribution. The VDMP CEST scheme consists of a train of RF pulses with a specific mixing time. The CEST signal with respect to the mixing time shows distinguishable characteristics for protons with different exchange rates. Exchange rate filtered CEST images are generated by subtracting images acquired at two mixing times at which the MTC signals are equal, while the APT and rNOE-CEST signals differ. Because the subtraction is performed at the same frequency offset for each voxel and the CEST signals are broad, no B0 correction is needed. MTC-suppressed APT and rNOE-CEST images of human brain were obtained using the VDMP method. The APT-CEST data show hyperintensity in gray matter versus white matter, whereas the rNOE-CEST images show negligible contrast between gray and white matter. The VDMP approach provides a simple and rapid way of recording MTC-suppressed APT-CEST and rNOE-CEST images without the need for B0 field correction. © 2015 Wiley Periodicals, Inc.

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.

[Study of dopamine transporter imaging on the brain of children with autism].

PubMed

Sun, Xiaomian; Yue, Jing; Zheng, Chongxun

2008-04-01

This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.

In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

PubMed

Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

2013-05-01

Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

PubMed

Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

2012-01-01

(18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders. Published by Elsevier Inc.

Intraoperative /sup 99m/Tc bone imaging in the treatment of benign osteoblastic tumors

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

Sty, J.; Simons, G.

1982-05-01

Benign bone tumors can be successfully treated by local resection with the use of intraoperative bone imaging. Intraoperative bone imaging provided accurate localization of an osteoid osteoma in a patella of a 16-year-old girl when standard radiographs failed to demonstrate the lesion. In a case of osteoblastoma of the sacrum in a 12-year old girl, intraoperative scanning was used repeatedly to guide completeness of resection. In these cases in which routine intraoperative radiographs would have failed, intraoperative scanning proved to be essential for success.

Nuclear cardiology

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

Willerson, J.T.

1979-01-01

Nuclear Cardiology is a well-written, concise compendium of chapters that covers a wide range of topics in nuclear cardiology. Each chapter has been contributed by one or more recognized experts in the field, and the work is thoroughly referened. The physics and physiology of nuclear cardiology, myocardial imaging with /sup 201/Tl and /sup 99m/Tc pyrophosphate, left ventricular and right ventricular function, measurement of coronary blood flow with /sup 133/Xe, and microspheres are discussed, and there are chapters on metabolic imaging with positron emitters and on transmission computerized tomography of the heart.

High Sensitivity SPECT for Small Animals and Plants

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

Mitchell, Gregory S.

Imaging systems using single gamma-ray emitting radioisotopes typically implement collimators in order to form the images. However, a tradeoff in sensitivity is inherent in the use of collimators, and modern preclinical single-photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma-rays (<0.3%). We have built a collimator-less system, which can reach sensitivity of 40% for 99mTc imaging, while still producing images of sufficient spatial resolution for certain applications in thin objects such as mice, small plants, and well plates used for in vitro experiments.

In vitro and in vivo evaluation of new radiolabeled neurotensin(8-13) analogues with high affinity for NT1 receptors.

PubMed

García-Garayoa, E; Allemann-Tannahill, L; Bläuenstein, P; Willmann, M; Carrel-Rémy, N; Tourwé, D; Iterbeke, K; Conrath, P; Schubiger, P A

2001-01-01

The potential utility of neurotensin (NT) in cancer diagnosis and therapy is limited by its rapid degradation. New stabilized analogues were synthesized, labeled with [99mTc] and screened in vitro and in vivo. High affinity and rapid internalization were obtained in binding assays. Despite their longer human plasma half-lives, a rapid degradation was observed with low concentrations as used in biodistribution tests. The tumor uptake rates were rather low but tumor/blood ratios increased according to the stability raise.

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

PubMed

Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G

2015-06-01

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

PubMed Central

Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

2015-01-01

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

Single isotope evaluation of pulmonary capillary protein leak (ARDS model) using computerized gamma scintigraphy

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

Tatum, J.L.; Strash, A.M.; Sugerman, H.J.

Using a canine oleic acid model, a computerized gamma scintigraphic technique was evaluated to determine 1) ability to detect pulmonary capillary protein leak in a model temporally consistent with clinical adult respiratory distress syndrome (ARDS), 2) the possibility of providing a quantitative index of leak, and 3) the feasibility of closely spaced repeat evaluations. Study animals received oleic acid (controls, n . 10; 0.05 ml/kg, n . 10; 0.10 ml/kg, n . 12; 0.15 ml/kg, n . 6) 3 hours prior to a tracer dose of technetium-99m (/sup 99/mTc) HSA. One animal in each dose group also received two repeatmore » tracer injections spaced a minimum of 45 minutes apart. Digital images were obtained with a conventional gamma camera interfaced to a dedicated medical computer. Lung: heart ratio versus time curves were generated, and a slope index was calculated for each curve. Slope index values for all doses were significantly greater than control values (P(t) less than 0.0001). Each incremental dose increase was also significantly greater than the previous dose level. Oleic acid dose versus slope index fitted a linear regression model with r . 0.94. Repeat dosing produced index values with standard deviations less than the group sample standard deviations. We feel this technique may have application in the clinical study of pulmonary permeability edema.« less

Impact of intracellular metallothionein on metal biouptake and partitioning dynamics at bacterial interfaces.

PubMed

Présent, Romain M; Rotureau, Elise; Billard, Patrick; Pagnout, Christophe; Sohm, Bénédicte; Flayac, Justine; Gley, Renaud; Pinheiro, José P; Duval, Jérôme F L

2017-11-08

Genetically engineered microorganisms are alternatives to physicochemical methods for remediation of metal-contaminated aquifers due to their remarkable bioaccumulation capacities. The design of such biosystems would benefit from the elaboration of a sound quantitative connection between performance in terms of metal removal from aqueous solution and dynamics of the multiscale processes leading to metal biouptake. In this work, this elaboration is reported for Escherichia coli cells modified to overexpress intracellular metallothionein (MTc), a strong proteinaceous metal chelator. Depletion kinetics of Cd(ii) from bulk solution following biouptake and intracellular accumulation is addressed as a function of cell volume fraction using electroanalytical probes and ligand exchange-based analyses. It is shown that metal biouptake in the absence and presence of MTc is successfully interpreted on the basis of a formalism recently developed for metal partitioning dynamics at biointerfaces with integration of intracellular metal speciation. The analysis demonstrates how fast sequestration of metals by intracellular MTc bypasses metal excretion (efflux) and enhances the rate of metal depletion to an extent such that complete removal is achieved at sufficiently large cell volume fractions. The magnitude of the stability constant of nanoparticulate metal-MTc complexes, as derived from refined analysis of macroscopic bulk metal depletion data, is further confirmed by independent electrochemical measurement of metal binding by purified MTc extracts.

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.

(99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab.

PubMed

Ma, Qingjie; Min, Kaiyin; Wang, Ting; Chen, Bin; Wen, Qiang; Wang, Fan; Ji, Tiefeng; Gao, Shi

2015-07-01

Functional imaging can help clinicians assess the individual response of advanced nonsquamous non-small cell lung cancer (NSCLC) to chemoradiation therapy plus bevacizumab. Our purpose is to investigate the ability of (99m)Tc-3PRGD2 single photon emission computed tomography/computed tomography (SPECT/CT) in predicting the early response to treatment. Patients with advanced nonsquamous NSCLC diagnosed by histological or cytological examination were imaged with (99m)Tc-3PRGD2 SPECT/CT at 3 time points: 1-3 days before the start of treatment (SPECT1), 40 Gy radiotherapy with 2 cycles of chemotherapy plus bevacizumab (SPECT2) and 4 weeks after chemoradiotherapy plus bevacizumab (SPECT3). The images were evaluated semiquantitatively by measuring the tumor to non-tumor ratio (T/N) and calculating the percentage change in T/N ratio. Short-term outcome was assessed by the treatment response evaluation according to the Response Evaluation Criteria in Solid Tumors criteria as: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were divided two groups: responders (CR and PR) and nonresponders (SD and PD). To determine a threshold for percent reduction in T/N ratios, receiver-operating characteristic (ROC) curve analysis was used. Patients were grouped again based on the threshold of P1 (the change percentage from SPECT1 to SPECT2) and P2 (the change percentage from SPECT1 to SPECT3): P1 responders and P1 nonresponders; P2 responders and P2 nonresponders. Patients were followed up starting 4 weeks after completion of therapy and then every 3 months for the first 2 years and every 6 months after 2 years. OS of P1 responders, P1 nonresponders, P2 responders and P2 nonresponders was estimated and graphically illustrated using the Kaplan-Meier method and the log-rank test was used to test the null hypotheses of equal OS in subgroups of patients. A total of 28 patients completed all imaging and treatment. All primary lung tumors were well visualized on SPECT1. The mean T/N ratio of SPECT1 in responders and nonresponders was not statistically different (2.73 ± 0.59 vs. 2.59 ± 0.52, p > 0.05). At SPECT2 and SPECT3, the mean T/N ratios were both lower in the responders compared with the nonresponders and had statistical significance (p < 0.05). P1 and P2 in the responders was larger than the nonresponders with significant difference (P1: 34.18 ± 21.55 % vs. 9.02 ± 14.02 %, p < 0.05; P2: 53.02 ± 15.50 % vs. 7.74 ± 37.95 %, p < 0.05). The optimal threshold of P1 that can discriminate between P1 responders and P1 nonresponders was greater than 25.9 % reduction, and that of P2 that can discriminate between P2 responders and P2 nonresponders was 34.0 % reduction. The area under the ROC curve (AUC) of P1 and P2 for determining residual disease was 0.856 and 0.909, respectively; but there was no statistical significance between them (p > 0.05). There was a significant difference for OS between P1 responders and P1 nonresponders (p < 0.05), and also for OS between P2 responders and P2 nonresponders (p < 0.05). But there was no difference between the P1 responders and P2 responders (p > 0.05), or between the P1 nonresponders and P2 nonresponders (p > 0.05). A (99m)Tc-3PRGD2 SPECT/CT after two cycles of chemoradiotherapy plus bevacizumab can predict patients who will have a better response to treatment and survival.

Novel alpha-MSH peptide analogs for melanoma targeting

NASA Astrophysics Data System (ADS)

Flook, Adam Michael

Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in-vivo tumor lesions with SPECT/CT. While all peptides exhibited high melanoma uptake, extremely high non-specific renal uptake was of concern. After synthesis of alpha-MSH peptide conjugates containing a different amino acid linker, renal uptake was drastically reduced and a lead compound had emerged, showing favorable in-vivo melanoma targeting and uptake properties with limited amounts of non-specific renal accumulation.

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.

Radiolabeled mannosylated dextran derivatives bearing an NIR-fluorophore for sentinel lymph node imaging.

PubMed

Morais, Maurício; Campello, Maria P C; Xavier, Catarina; Heemskerk, Johannes; Correia, João D G; Lahoutte, Tony; Caveliers, Vicky; Hernot, Sophie; Santos, Isabel

2014-11-19

Current methods for sentinel lymph node (SLN) mapping involve the use of radioactivity detection with technetium-99m sulfur colloid and/or visually guided identification using a blue dye. To overcome the kinetic variations of two individual imaging agents through the lymphatic system, we report herein on two multifunctional macromolecules, 5a and 6a, that contain a radionuclide ((99m)Tc or (68)Ga) and a near-infrared (NIR) reporter for pre- and/or intraoperative SLN mapping by nuclear and NIR optical imaging techniques. Both bimodal probes are dextran-based polymers (10 kDa) functionalized with pyrazole-diamine (Pz) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelating units for labeling with fac-[(99m)Tc(CO)3](+) or (68)Ga(III), respectively, mannose units for receptor targeting, and NIR fluorophore units for optical imaging. The probes allowed a clear visualization of the popliteal node by single-photon emission computed tomography (SPECT/CT) or positron emission tomography (PET/CT), as well as real-time optically guided excision. Biodistribution studies confirmed that both macromolecules present a significant accumulation in the popliteal node (5a: 3.87 ± 0.63% IA/organ; 6a: 1.04 ± 0.26% IA/organ), with minimal spread to other organs. The multifunctional nanoplatforms display a popliteal extraction efficiency >90%, highlighting their potential to be further explored as dual imaging agents.

Disease-modifying polymorphisms and C609Y mutation of RET associated with high penetrance of phaeochromocytoma and low rate of MTC in MEN2A.

PubMed

Speak, Rowena; Cook, Jackie; Harrison, Barney; Newell-Price, John

2016-01-01

Mutations of the rearranged during transfection ( RET ) proto-oncogene, located on chromosome 10q11.2, cause multiple endocrine neoplasia type 2A (MEN2A). Patients with mutations at the codon 609 usually exhibit a high penetrance of medullary thyroid cancer (MTC), but a sufficiently low penetrance of phaeochromocytoma that screening for this latter complication has been called to question. Patients with other RET mutations are at higher risk of younger age onset phaeochromocytoma if they also possess other RET polymorphisms (L769L, S836S, G691S and S904S), but there are no similar data for patients with 609 mutations. We investigated the unusual phenotypic presentation in a family with MEN2A due to a C609Y mutation in RET . Sanger sequencing of the entire RET -coding region and exon-intron boundaries was performed. Five family members were C609Y mutation positive: 3/5 initially presented with phaeochromocytoma, but only 1/5 had MTC. The index case aged 73 years had no evidence of MTC, but presented with phaeochromocytoma. Family members also possessed the G691S and S904S RET polymorphisms. We illustrate a high penetrance of phaeochromocytoma and low penetrance of MTC in patients with a RET C609Y mutation and polymorphisms G691S and S904S. These data highlight the need for life-long screening for the complications of MEN2A in these patients and support the role for the screening of RET polymorphisms for the purposes of risk stratification. C609Y RET mutations may be associated with a life-long risk of phaeochromocytoma indicating the importance of life-long screening for this condition in patients with MEN2A.C609Y RET mutations may be associated with a lower risk of MTC than often quoted, questioning the need for early prophylactic thyroid surgery discussion at the age of 5 years.There may be a role for the routine screening of RET polymorphisms, and this is greatly facilitated by the increasing ease of access to next-generation sequencing.

Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

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

Groeneveld, A.B.; den Hollander, W.; Straub, J.

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interestmore » were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N.« less

Influence of Decontaminating Agents and Swipe Materials on Laboratory Simulated Working Surfaces Wet Spilled with Sodium Pertechnetate.

PubMed

Akchata, Suman; Lavanya, K; Shivanand, Bhushan

2017-01-01

Decontamination of various working surfaces with sodium pertechnetate minor spillage is essential for maintaining good radiation safety practices as well as for regulatory compliance. To observe the influences of decontaminating agents and swipe materials on different type of surfaces used in nuclear medicine laboratory work area wet spilled with 99m-technetium (99mTc) sodium pertechnetate. Lab-simulated working surface materials. Experimental study design. Direct decontamination method on dust-free lab simulated new working surfaces [stainless steel, polyvinyl chloride (PVC), Perspex, resin] using four decontaminating agents [tap water, soap water (SW), Radiacwash, and spirit] with four different swipe material [cotton, tissue paper (TP), Whatman paper (WP), adsorbent sheet (AS)] was taken 10 samples (n = 10) for each group. Parametric test two-way analysis of variance is used with significance level of 0.005, was used to evaluate statistical differences between different group of decontaminating agent and swipe material, and the results are expressed in mean ± SD. Decontamination factor is calculated after five cleaning for each group. A total of 160 samples result calculated using four decontaminating agent (tap water, SW, Radiacwash, and spirit), four swipe material (cotton, TP, WP, and AS) for commonly used surface (stainless steel, PVC, Perspex, resin) using direct method by 10 samples (n = 10) for each group. Tap water is the best decontaminating agent compared with SW, Radiac wash and spirit for the laboratory simulated stainless steel, PVC, and Perspex surface material, whereas in case of resin surface material, SW decontaminating agent is showing better effectiveness. Cotton is the best swipe material compared to WP-1, AS and TP for the stainless steel, PVC, Perspex, and resin laboratory simulated surface materials. Perspex and stainless steel are the most suitable and recommended laboratory surface material compared to PVC and resin in nuclear medicine. Radiacwash may show better result for 99mTc labelled product and other radionuclide contamination on the laboratory working surface area.

Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer.

PubMed

Borrego, Salud; Fernández, Raquel M; Dziema, Heather; Japón, Miguel A; Marcos, Irene; Eng, Charis; Antiñolo, Guillermo

2002-11-01

The etiology of sporadic medullary thyroid carcinoma (sMTC) remains elusive. While germline gain-of-function mutations in the RET proto-oncogene cause hereditary MTC, somatic RET mutations have been described in a variable number of sMTC. So far, S836S of RET, is the only variant whose association with sMTC has been found in several European cohorts. Because RET variants seem to be associated with MTC, it is plausible that variants in genes encoding for RET coreceptors may play a role in the pathogenesis of sMTC. Recently, we described two possible low penetrance susceptibility alleles in the gene encoding RET coreceptor GFRalpha1, -193C > G and 537T > C, in a German series of sMTC. In this study, we have genotyped nine polymorphisms within GFRA1-3 genes for 51 Spanish sMTC, and 100 normal controls. Our results show that no statistical signification was found when Spanish sMTC patients were compared to controls. Taken together with the observations in the German sMTC series, the present findings suggest that GFRA1-193C > G and 537T > C could be in linkage disequilibrium with other loci responsible for the disease with a founder effect in Germany. Alternatively, the combined observations might also suggest that, if indeed the polymorphisms are functional, the effect is small.

The NIST radioactivity measurement assurance program for the radiopharmaceutical industry.

PubMed

Cessna, Jeffrey T; Golas, Daniel B

2012-09-01

The National Institute of Standards and Technology (NIST) maintains a program for the establishment and dissemination of activity measurement standards in nuclear medicine. These standards are disseminated through Standard Reference Materials (SRMs), Calibration Services, radionuclide calibrator settings, and the NIST Radioactivity Measurement Assurance Program (NRMAP, formerly the NEI/NIST MAP). The MAP for the radiopharmaceutical industry is described here. Consolidated results show that, for over 3600 comparisons, 96% of the participants' results differed from that of NIST by less than 10%, with 98% being less than 20%. Individual radionuclide results are presented from 214 to 439 comparisons, per radionuclide, for (67)Ga, (90)Y, (99m)Tc, (99)Mo, (111)In, (125)I, (131)I, and (201)Tl. The percentage of participants results within 10% of NIST ranges from 88% to 98%. Published by Elsevier Ltd.

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

PubMed Central

Choi, Ji Young; Iacobazzi, Rosa Maria; Perrone, Mara; Margiotta, Nicola; Cutrignelli, Annalisa; Jung, Jae Ho; Park, Do Dam; Moon, Byung Seok; Denora, Nunzio; Kim, Sang Eun; Lee, Byung Chul

2016-01-01

The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. 99mTc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [99mTc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that 99mTc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation. PMID:27399688

Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation.

PubMed

Thurgar, Elizabeth; Barton, Samantha; Karner, Charlotta; Edwards, Steven J

2016-03-01

Typically occurring on the external genitalia, anogenital warts (AGWs) are benign epithelial skin lesions caused by human papillomavirus infection. AGWs are usually painless but can be unsightly and physically uncomfortable, and affected people might experience psychological distress. The evidence base on the clinical effectiveness and cost-effectiveness of treatments for AGWs is limited. To systematically review the evidence on the clinical effectiveness of medical and surgical treatments for AGWs and to develop an economic model to estimate the cost-effectiveness of the treatments. Electronic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Web of Science) were searched from inception (or January 2000 for Web of Science) to September 2014. Bibliographies of relevant systematic reviews were hand-searched to identify potentially relevant studies. The World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov were searched for ongoing and planned studies. A systematic review of the clinical effectiveness literature was carried out according to standard methods and a mixed-treatment comparison (MTC) undertaken. The model implemented for each outcome was that with the lowest deviance information criterion. A de novo economic model was developed to assess cost-effectiveness from the perspective of the UK NHS. The model structure was informed through a systematic review of the economic literature and in consultation with clinical experts. Effectiveness data were obtained from the MTC. Costs were obtained from the literature and standard UK sources. Of 4232 titles and abstracts screened for inclusion in the review of clinical effectiveness, 60 randomised controlled trials (RCTs) evaluating 19 interventions were included. Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of treatment. Podophyllotoxin 0.5% solution (Condyline(®), Takeda Pharmaceutical Company Ltd; Warticon(®) solution, Stiefel Laboratories Ltd) was found to be the most effective topical treatment evaluated. Networks for other outcomes included fewer treatments, which restrict conclusions on the comparative effectiveness of interventions. In total, 84 treatment strategies were assessed using the economic model. Podophyllotoxin 0.5% solution first line followed by carbon dioxide (CO2) laser therapy second line if AGWs did not clear was most likely to be considered a cost-effective use of resources at a willingness to pay of £20,000-30,000 per additional quality-adjusted life-year gained. The result was robust to most sensitivity analyses conducted. Limited reporting in identified studies of baseline characteristics for the enrolled population generates uncertainty around the comparability of the study populations and therefore the generalisability of the results to clinical practice. Subgroup analyses were planned based on type, number and size of AGWs, all of which are factors thought to influence treatment effect. Lack of data on clinical effectiveness based on these characteristics precluded analysis of the differential effects of treatments in the subgroups of interest. Despite identification of 60 studies, most comparisons in the MTC are informed by only one RCT. Additionally, lack of head-to-head RCTs comparing key treatments, together with minimal reporting of results in some studies, precluded comprehensive analysis of all treatments for AGWs. The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinically more effective at completely clearing AGWs after treatment. However, the evidence base informing the MTC is limited. A head-to-head RCT that evaluates the comparative effectiveness of interventions used in clinical practice would help to discern the potential advantages and disadvantages of the individual treatments. The results of the economic analysis suggest that podophyllotoxin 0.5% solution is likely to represent a cost-effective first-line treatment option. More expensive effective treatments, such as CO2 laser therapy or surgery, may represent cost-effective second-line treatment options. No treatment and podophyllin are unlikely to be considered cost-effective treatment options. There is uncertainty around the cost-effectiveness of treatment with imiquimod, trichloroacetic acid and cryotherapy. This study is registered as PROSPERO CRD42013005457. The National Institute for Health Research Health Technology Assessment programme.

How a tertiary medical nuclear medicine department at the Himalayan area in India can be established and function in an exemplary manner. Basic rules revisited.

PubMed

Dhingra, Vandana Kumar; Saini, Sunil; Basu, Sandip

2015-01-01

We describe and discuss the various medical, social and financial aspects of setting up, and optimizing, working conditions of a tertiary Nuclear Medicine Department. This department was established in a North Indian state which comprises 93% of hilly area. During the first three years after establishment we have developed infrastructure, cooperation with other departments, improved radiation safety and cost effectiveness of our work and designed future perspectives. The facility was established in a cancer center of a tertiary care hospital where a medical college infrastructure was developed. National guidelines formulated by the Atomic Energy Regulatory Board (AERB) were followed. Our department served a population area of 10.08 million inhabitants. Over the first three years 2,400 patients underwent diagnostic scans and 106 patients underwent low dose radioiodine treatment for thyrotoxicosis. To optimize resources and at the same time, enhance their effectivity, we procured our (99)Mo/ (99m)Tc generator every other week and arranged our daily programme accordingly. Fractionation of cold kits allowed us to perform low cost in-vivo procedures on a daily basis and to save the department's running costs by 30%-50%. We run continuing education nuclear medicine programmes for referring physicians, medical students and paramedical workers which were included in routine practice which led to a consistent growth in patients referral. The need for a positron emission tomography/computed tomography (PET/CT) scan and high dose treatment department for thyroid cancer was strongly felt. Our nuclear medicine department in a peripheral region of a developing country applied better logistics by procuring new generator every fortnight, fractionating the cold kits and by organizing complete teaching programmes.

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.

Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

PubMed

Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

2002-11-06

In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.

PubMed

Deiana, Serena; Harrington, Charles R; Wischik, Claude M; Riedel, Gernot

2009-01-01

The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.

IDACstar: A MCNP Application to Perform Realistic Dose Estimations from Internal or External Contamination of Radiopharmaceuticals.

PubMed

Ören, Ünal; Hiller, Mauritius; Andersson, M

2017-04-28

A Monte Carlo-based stand-alone program, IDACstar (Internal Dose Assessment by Computer), was developed, dedicated to perform radiation dose calculations using complex voxel simulations. To test the program, two irradiation situations were simulated, one hypothetical contamination case with 600 MBq of 99mTc and one extravasation case involving 370 MBq of 18F-FDG. The effective dose was estimated to be 0.042 mSv for the contamination case and 4.5 mSv for the extravasation case. IDACstar has demonstrated that dosimetry results from contamination or extravasation cases can be acquired with great ease. An effective tool for radiation protection applications is provided with IDACstar allowing physicists at nuclear medicine departments to easily quantify the radiation risk of stochastic effects when a radiation accident has occurred. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

2D dose distribution images of a hybrid low field MRI-γ detector

NASA Astrophysics Data System (ADS)

Abril, A.; Agulles-Pedrós, L.

2016-07-01

The proposed hybrid system is a combination of a low field MRI and dosimetric gel as a γ detector. The readout system is based on the polymerization process induced by the gel radiation. A gel dose map is obtained which represents the functional part of hybrid image alongside with the anatomical MRI one. Both images should be taken while the patient with a radiopharmaceutical is located inside the MRI system with a gel detector matrix. A relevant aspect of this proposal is that the dosimetric gel has never been used to acquire medical images. The results presented show the interaction of the 99mTc source with the dosimetric gel simulated in Geant4. The purpose was to obtain the planar γ 2D-image. The different source configurations are studied to explore the ability of the gel as radiation detector through the following parameters; resolution, shape definition and radio-pharmaceutical concentration.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis.

PubMed

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC 50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

Multibus-based parallel processor for simulation

NASA Technical Reports Server (NTRS)

Ogrady, E. P.; Wang, C.-H.

1983-01-01

A Multibus-based parallel processor simulation system is described. The system is intended to serve as a vehicle for gaining hands-on experience, testing system and application software, and evaluating parallel processor performance during development of a larger system based on the horizontal/vertical-bus interprocessor communication mechanism. The prototype system consists of up to seven Intel iSBC 86/12A single-board computers which serve as processing elements, a multiple transmission controller (MTC) designed to support system operation, and an Intel Model 225 Microcomputer Development System which serves as the user interface and input/output processor. All components are interconnected by a Multibus/IEEE 796 bus. An important characteristic of the system is that it provides a mechanism for a processing element to broadcast data to other selected processing elements. This parallel transfer capability is provided through the design of the MTC and a minor modification to the iSBC 86/12A board. The operation of the MTC, the basic hardware-level operation of the system, and pertinent details about the iSBC 86/12A and the Multibus are described.

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

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

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

Determination of the influence factors of the radiopharmaceutical vials dimensions used for activimeter calibration at IPEN.

PubMed

Martins, E W; Potiens, M P A

2012-07-01

This paper presents the establishment of a quality control program and correction factors for the geometry of the vials used for distribution of radiopharmaceutical and activimeters calibration. The radiopharmaceutical produced by IPEN 67Ga, 131I, 201Tl and 99mTc had been tested using two different vials. Results show a maximum variation of 22% for 201Tl, and the minimum variation was 2.98% for 131I. The correction factors must be incorporated in the routine calibration of the activimeters. Copyright © 2011 Elsevier Ltd. All rights reserved.

Intra-articular triamcinolone hexacetonide and osmic acid in persistent synovitis of the knee.

PubMed

Anttinen, J; Oka, M

1975-01-01

43 rheumatoid knees with persistent effusion were treated by intra-articular injections of triamcinolone hexacetonide (40 mg) or combined triamcinolone - osmic acid. Both treatments produced long-lasting improvements in the treated knees. Osmic acid seemed to potentiate the effect of the steroid. This demonstrated by measurement of joint circumference and local 99mTc uptake. In the general clinical evaluation the difference between the treatments was not noticeable. The percentage of 'excellent' and 'good' improvements was 36 at 12 months in the steroid-group and 44 in the steroid-osmic acid group.

Development of a high performance (188)W/(188)Re generator by using a synthetic alumina.

PubMed

Lee, Jun Sig; Lee, Jong-Soup; Park, Ul-Jae; Son, Kwang-Jae; Han, Hyon-Soo

2009-01-01

A synthetic alumina functionalized with a sulfate moiety has been developed as the column material of (99)Mo/(99m)Tc and (188)W/(188)Re generators. This material is synthesized by a sol-gel processing. In order to characterize the adsorbent for the (188)W/(188)Re separation, both batch and column contact experiments were conducted. As a result of the experiments, it is found that the maximum capacity of the adsorbent for tungsten is higher than 450mg/g. Hence it is possible to produce approximately 3Ci (188)W/(188)Re generator with only 1g of the adsorbent from (188)W solutions supplied from ORNL, USA or RIAR, Russia. A demonstration study was conducted to show the performance of an (188)W/(188)Re generator column. In this study, 1Ci of (188)W purchased from RIAR, Russia, is loaded on a 0.9cm ID column packed with 0.7g of the adsorbent. Elution of (188)Re is performed every 4-7 days by using the saline solution for more than three months. Nearly 100% of tungsten is loaded by passing 5ml of the (188)W solution (pH=8) through the dry packed column at a 1ml/min flow rate. Elution efficiency of (188)Re is 70-90% by using 5ml of the saline solution. The ratio of (188)W/(188)Re in the eluted solution is 0.002-0.003%. When a Sep-Pak containing 0.26g of acid alumina is installed as a tandem column, the ratio is decreased to less than 10(-3)%. Thin layer chromatography for the eluted (188)Re solution shows 100% radiochemical purity. Also, alumina content in the eluted solution shows less than 10ppm. Through this study, the performance of this adsorbent was successfully demonstrated. By using the developed adsorbent, minimization of the generator column and consequently the volume of eluant could be possible while maintaining the quality of (188)Re just as much as that available in the market.

Serum level of vascular endothelial growth factor is influenced by erythropoietin treatment in peritoneal dialysis patients. (Grupo de Estudios Peritoneales de Madrid).

PubMed

del Peso, G; Selgas, R; Bajo, M A; Fernández de Castro, M; Aguilera, A; Cirugeda, A; Jiménez, C

2000-01-01

Some patients on long-term peritoneal dialysis (PD) develop a hyperpermeability state, owing to peritoneal neoangiogenesis. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, has been implicated in most diseases characterized by microvascular neoformation. Erythropoietin (EPO) is able to induce endothelial proliferation in vitro. Our aim was to elucidate whether VEGF serum levels are influenced by EPO treatment, and whether VEGF serum level maintains a relationship with peritoneal transport data. We analyzed serum levels of VEGF in 35 PD patients (18 males, 17 females). Mean age was 58 years, with a mean time on PD of 98 +/- 75 months. Of the 35 patients, 19 were on automated peritoneal dialysis, and 16 were on continuous ambulatory peritoneal dialysis. Seven patients had diabetes. Peritoneal transport parameters were: urea mass transfer coefficient (MTC), 19.5 +/- 6.6 mL/min; creatinine MTC, 9.9 +/- 4.7 mL/min; net ultrafiltration, 491 +/- 166 mL per 4-hour dwell. Twenty seven patients were under therapy with recombinant human erythropoietin (rHuEPO). Mean serum VEGF levels were 347 +/- 203 pg/mL (range 66-857 pg/mL), with most patients in the normal range (60-700 pg/mL). VEGF levels did not correlate with age, sex, primary renal disease, diabetes, type of PD, time on PD, peritonitis, and cumulative glucose load. We found no correlation with urea MTC, creatinine MTC, ultrafiltration rate, or protein effluent levels. However, a significant negative correlation with residual renal function was seen (r = -0.39, p < 0.05). Patients treated with rHuEPO showed significantly higher serum levels of VEGF than non treated patients (375 +/- 220 pg/mL vs 251 +/- 75 pg/mL, p < 0.05), although they had similar residual renal function. We conclude that increased serum VEGF levels are associated with EPO treatment. Consequently, VEGF might have a role in the EPO effects found in PD patients. Whether both agents are related to peritoneal neoangiogenesis requires further research.

Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor.

PubMed Central

Stolk, J.; Camps, J.; Feitsma, H. I.; Hermans, J.; Dijkman, J. H.; Pauwels, E. K.

1995-01-01

BACKGROUND--The neutrophil elastase inhibitor, secretory leucocyte protease inhibitor (SLPI), is a potential therapeutic tool in inflammatory lung diseases such as cystic fibrosis and pulmonary emphysema. The distribution and disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was investigated in healthy humans and in patients with cystic fibrosis or alpha 1-antitrypsin-associated emphysema. METHODS--To distinguish aerosolised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI in the lungs were studied by gamma radiation imaging. RESULTS--The deposition of 99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in patients with cystic fibrosis or emphysema only well ventilated areas showed deposition of the aerosol. The disappearance rate of 99mTc-rSLPI was biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of the slow phase was more than 24 hours. CONCLUSIONS--Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrophil derived elastase. It may be more difficult to neutralise the burden of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis. Images PMID:7638807

The separation of 99Tc from low and medium-level radioactive wastes and its determination by inductively coupled plasma mass spectrometry.

PubMed

Hepiegne, P; Dall'ava, D; Clement, R; Degros, J P

1995-06-01

A chemical separation method has been developed for the determination of (99)Tc in various types of radioactive wastes. Such a method includes (i) fusion with NaOH, (ii) extraction in a column containing methyltrioctylammonium chloride, (iii) extraction by solvent with N-benzoyl-N-phenylhydroxylamine and, (iv) measurement by inductively-coupled plasma mass spectrometry (ICP-MS). From the performance standpoint, the recovery of (99)Tc, using (99m)Tc as a yield tracer, is higher than 70%. This analytical method, as developed, ensures effective decontamination with respect to the radionuclides, insofar the decontamination factors are greater than 10(+5), whenever the residual activity may be measured. Taking into account a 3sigma counting error, the detection limit obtained with the ICP-MS technique is 1.9 mBq/ml; the method enabling hence to detect activities as low as 0.3 Bq/g, with analysed samples of 0.2 g and a radiochemical yield of 70%. Studies have been dedicated to the (99)Tc measurement, using the electrothermal vaporization ICP-MS technique, which lowers the detection limit by a factor 10, with the standard solution (0.3 pg/ml), compared with the previous ICP-MS technique.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

PubMed

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

Investigation of the MTC noise estimation with a coupled neutronic/thermal-hydraulic dedicated model - 'Closing the loop'

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

Demaziere, C.; Larsson, V.

2012-07-01

This paper investigates the reliability of different noise estimators aimed at determining the Moderator Temperature Coefficient (MTC) of reactivity in Pressurized Water Reactors. By monitoring the inherent fluctuations in the neutron flux and moderator temperature, an on-line monitoring of the MTC without perturbing reactor operation is possible. In order to get an accurate estimation of the MTC by noise analysis, the point-kinetic component of the neutron noise and the core-averaged moderator temperature noise have to be used. Because of the scarcity of the in-core instrumentation, the determination of these quantities is difficult, and several possibilities thus exist for estimating themore » MTC by noise analysis. Furthermore, the effect of feedback has to be negligible at the frequency chosen for estimating the MTC in order to get a proper determination of the MTC. By using an integrated neutronic/thermal- hydraulic model specifically developed for estimating the three-dimensional distributions of the fluctuations in neutron flux, moderator properties, and fuel temperature, different approaches for estimating the MTC by noise analysis can be tested individually. It is demonstrated that a reliable MTC estimation can only be provided if the core is equipped with a sufficient number of both neutron detectors and temperature sensors, i.e. if the core contain in-core detectors monitoring both the axial and radial distributions of the fluctuations in neutron flux and moderator temperature. It is further proven that the effect of feedback is negligible for frequencies higher than 0.1 Hz, and thus the MTC noise estimations have to be performed at higher frequencies. (authors)« less

The impact of major trauma network triage systems on patients with major burns.

PubMed

Nizamoglu, Metin; O'Connor, Edmund Fitzgerald; Bache, Sarah; Theodorakopoulou, Evgenia; Sen, Sankhya; Sherren, Peter; Barnes, David; Dziewulski, Peter

2016-12-01

Trauma is a leading cause of death and disability worldwide. Patients presenting with severe trauma and burns benefit from specifically trained multidisciplinary teams. Regional trauma systems have shown improved outcomes for trauma patients. The aim of this study is to determine whether the development of major trauma systems have improved the management of patients with major burns. A retrospective study was performed over a four-year period reviewing all major burns in adults and children received at a regional burns centre in the UK before and after the implementation of the regional trauma systems and major trauma centres (MTC). Comparisons were drawn between three areas: (1) Patients presenting before the introduction of MTC and after the introduction of MTC. (2) Patients referred from MTC and non-MTC within the region, following the introduction of MTC. (3) Patients referred using the urban trauma protocol and the rural trauma protocol. Following the introduction of regional trauma systems and major trauma centres (MTC), isolated burn patients seen at our regional burns centre did not show any significant improvement in transfer times, admission resuscitation parameters, organ dysfunction or survival when referred from a MTC compared to a non-MTC emergency department. There was also no significant difference in survival when comparing referrals from all hospitals pre and post establishment of the major trauma network. No significant outcome benefit was demonstrated for burns patients referred via MTCs compared to non-MTCs. We suggest further research is needed to ascertain whether burns patients benefit from prolonged transfer times to a MTC compared to those seen at their local hospitals prior to transfer to a regional burns unit for further specialist care. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

PubMed Central

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages. PMID:27879160

Widespread Environmental Contamination with Mycobacterium tuberculosis Complex Revealed by a Molecular Detection Protocol

PubMed Central

Santos, Nuno; Santos, Catarina; Valente, Teresa; Gortázar, Christian; Almeida, Virgílio; Correia-Neves, Margarida

2015-01-01

Environmental contamination with Mycobacterium tuberculosis complex (MTC) has been considered crucial for bovine tuberculosis persistence in multi-host-pathogen systems. However, MTC contamination has been difficult to detect due to methodological issues. In an attempt to overcome this limitation we developed an improved protocol for the detection of MTC DNA. MTC DNA concentration was estimated by the Most Probable Number (MPN) method. Making use of this protocol we showed that MTC contamination is widespread in different types of environmental samples from the Iberian Peninsula, which supports indirect transmission as a contributing mechanism for the maintenance of bovine tuberculosis in this multi-host-pathogen system. The proportion of MTC DNA positive samples was higher in the bovine tuberculosis-infected than in presumed negative area (0.32 and 0.18, respectively). Detection varied with the type of environmental sample and was more frequent in sediment from dams and less frequent in water also from dams (0.22 and 0.05, respectively). The proportion of MTC-positive samples was significantly higher in spring (p<0.001), but MTC DNA concentration per sample was higher in autumn and lower in summer. The average MTC DNA concentration in positive samples was 0.82 MPN/g (CI95 0.70–0.98 MPN/g). We were further able to amplify a DNA sequence specific of Mycobacterium bovis/caprae in 4 environmental samples from the bTB-infected area. PMID:26561038

Midwest Transportation Consortium : 2004-2005 annual report.

DOT National Transportation Integrated Search

2005-01-01

Introduction: The Midwest Transportation Consortium (MTC) recently completed its sixth year of : operation. The MTC has become an established portion of the research and educational : programs at ISU and its partner universities. The MTC continues to...

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

PubMed

Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi

2017-02-01

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.

Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging

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

Russo, Paolo; Curion, Assunta S.; Mettivier, Giovanni

2011-03-15

Purpose: The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. Methods: The room-temperature CdTe pixel detector (1 mm thick) has 256x256 square pixels arranged with a 55 {mu}m pitch (sensitive area 14.08x14.08 mm{sup 2}), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diametermore » at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. Results: For {sup 99m}Tc, at 50 mm distance, a background-subtracted sensitivity of 6.5x10{sup -3} cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3x10{sup -2} cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq {sup 99m}Tc and prior localization with standard gamma camera lymphoscintigraphy. Conclusions: The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.« less

Bone-seeking TRAP conjugates: surprising observations and their implications on the development of gallium-68-labeled bisphosphonates

PubMed Central

2012-01-01

Background Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable. Findings Two trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga-71 nuclear magnetic resonance data prove that Ga(III) is not located in the chelating cavity of TRAP and must therefore be bound by the conjugated bisphosphonate units. Conclusion The intrinsic Ga-68 chelating properties of TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga-68-based bone seekers for PET, it appears sufficient to equip branched scaffolds with multiple bisphosphonate units, which serve both Ga-68-binding and bone-targeting purposes. PMID:22464278

[Restoration filtering based on projection power spectrum for single-photon emission computed tomography].

PubMed

Kubo, N

1995-04-01

To improve the quality of single-photon emission computed tomographic (SPECT) images, a restoration filter has been developed. This filter was designed according to practical "least squares filter" theory. It is necessary to know the object power spectrum and the noise power spectrum. The power spectrum is estimated from the power spectrum of a projection, when the high-frequency power spectrum of a projection is adequately approximated as a polynomial exponential expression. A study of the restoration with the filter based on a projection power spectrum was conducted, and compared with that of the "Butterworth" filtering method (cut-off frequency of 0.15 cycles/pixel), and "Wiener" filtering (signal-to-noise power spectrum ratio was a constant). Normalized mean-squared errors (NMSE) of the phantom, two line sources located in a 99mTc filled cylinder, were used. NMSE of the "Butterworth" filter, "Wiener" filter, and filtering based on a power spectrum were 0.77, 0.83, and 0.76 respectively. Clinically, brain SPECT images utilizing this new restoration filter improved the contrast. Thus, this filter may be useful in diagnosis of SPECT images.

Extravasation of a therapeutic dose of 131I-metaiodobenzylguanidine: prevention, dosimetry, and mitigation.

PubMed

Bonta, Dacian V; Halkar, Raghuveer K; Alazraki, Naomi

2011-09-01

After the extravasation of a therapeutic dose of (131)I-metaiodobenzylguanidine that produced a radiation burn to a patient's forearm, we instituted a catheter placement verification protocol. Before therapy infusion, proper placement is verified by administering 37 MBq of (99m)Tc-pertechnetate through the catheter, and monitoring activity at the administration site and on the contralateral extremity. A dosimetric model describing both high-rate and low-rate dose components was developed and predicted that the basal epidermal layer received a radiation dose consistent with the observed moist desquamation radiation skin toxicity. No extravasation incidents have occurred since the verification procedure was instituted. To protect against radiation injury from extravasation of therapeutic radionuclides, test administration of a small (99m)Tc dose with probe monitoring of comparable sites in both upper extremities appears to be an effective preventive measure.

A gluten-free vegan meal for gastric emptying scintigraphy: establishment of reference values and its utilization in the evaluation of diabetic gastroparesis.

PubMed

Somasundaram, Vijay Harish; Subramanyam, Padma; Palaniswamy, Shanmuga Sundaram

2014-11-01

The aim of this study was to describe the preparation of radiolabeled idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS) meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study was to establish normal emptying rates for this meal and present our experience in using it in the evaluation of diabetic gastroparesis. The meal was prepared using a universally available packaged mix labeled with 1 mCi 99mTc sulfur colloid, and the stability of labeling was tested up to 4 hours in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20-78 years; 54 women, 59 men) underwent GES study using the idli meal. Gastric retention at one-half, 1, 2, and 4 hours after ingestion of the meal was estimated, and the normal limits were set using the fifth and 95th percentile values at each period. Having established its normal emptying rates, the idli meal was further used to evaluate 70 patients suspected with diabetic gastroparesis. The idli meal, with a calorific value ≈282 kcal, has a relatively higher fat content (8% of total mass) than EWS. More than 96% of 99mTc sulfur colloid remained bound to the meal after 4 hours suspension in simulated gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours and 4 hours, respectively, indicated delayed gastric emptying, whereas retention less than 30% at 1 hour suggested rapid emptying. Among patients suspected with diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid emptying was seen in 4.2%. Radiolabeled idli meal is a good alternative to EWS meal for routine GES, especially among patients with specific dietary restrictions.

Imaging of spatially extended hot spots with coded apertures for intra-operative nuclear medicine applications

NASA Astrophysics Data System (ADS)

Kaissas, I.; Papadimitropoulos, C.; Potiriadis, C.; Karafasoulis, K.; Loukas, D.; Lambropoulos, C. P.

2017-01-01

Coded aperture imaging transcends planar imaging with conventional collimators in efficiency and Field of View (FOV). We present experimental results for the detection of 141 keV and 122 keV γ-photons emitted by uniformly extended 99mTc and 57Co hot-spots along with simulations of uniformly and normally extended 99mTc hot-spots. These results prove that the method can be used for intra-operative imaging of radio-traced sentinel nodes and thyroid remnants. The study is performed using a setup of two gamma cameras, each consisting of a coded-aperture (or mask) of Modified Uniformly Redundant Array (MURA) of rank 19 positioned on top of a CdTe detector. The detector pixel pitch is 350 μm and its active area is 4.4 × 4.4 cm2, while the mask element size is 1.7 mm. The detectable photon energy ranges from 15 keV up to 200 keV with an energy resolution of 3-4 keV FWHM. Triangulation is exploited to estimate the 3D spatial coordinates of the radioactive spots within the system FOV. Two extended sources, with uniform distributed activity (11 and 24 mm in diameter, respectively), positioned at 16 cm from the system and with 3 cm distance between their centers, can be resolved and localized with accuracy better than 5%. The results indicate that the estimated positions of spatially extended sources lay within their volume size and that neighboring sources, even with a low level of radioactivity, such as 30 MBq, can be clearly distinguished with an acquisition time about 3 seconds.

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

PubMed

Newberg, Andrew B; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S; Wintering, Nancy

2014-01-01

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to measure cerebral blood flow (CBF) and (123)I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand.

PubMed

Kularatne, Sumith A; Wang, Kevin; Santhapuram, Hari-Krishna R; Low, Philip S

2009-01-01

Prostate cancer (PCa) is a major cause of mortality and morbidity in Western society today. Current methods for detecting PCa are limited, leaving most early malignancies undiagnosed and sites of metastasis in advanced disease undetected. Major deficiencies also exist in the treatment of PCa, especially metastatic disease. In an effort to improve both detection and therapy of PCa, we have developed a PSMA-targeted ligand that delivers attached imaging and therapeutic agents selectively to PCa cells without targeting normal cells. The PSMA-targeted radioimaging agent (DUPA-(99m)Tc) was found to bind PSMA-positive human PCa cells (LNCaP cell line) with nanomolar affinity (K(D) = 14 nM). Imaging and biodistribution studies revealed that DUPA-(99m)Tc localizes primarily to LNCaP cell tumor xenografts in nu/nu mice (% injected dose/gram = 11.3 at 4 h postinjection; tumor-to-muscle ratio = 75:1). Two PSMA-targeted optical imaging agents (DUPA-FITC and DUPA-rhodamine B) were also shown to efficiently label PCa cells and to internalize and traffic to intracellular endosomes. A PSMA-targeted chemotherapeutic agent (DUPA-TubH) was demonstrated to kill PSMA-positive LNCaP cells in culture (IC(50) = 3 nM) and to eliminate established tumor xenografts in nu/nu mice with no detectable weight loss. Blockade of tumor targeting upon administration of excess PSMA inhibitor (PMPA) and the absence of targeting to PSMA-negative tumors confirmed the specificity of each of the above targeted reagents for PSMA. Tandem use of the imaging and therapeutic agents targeted to the same receptor could allow detection, staging, monitoring, and treatment of PCa with improved accuracy and efficacy.

Experimental Study of Nasopharyngeal Carcinoma Radionuclide Imaging and Therapy Using Transferred Human Sodium/Iodide Symporter Gene

PubMed Central

Zhong, Xing; Shi, Changzheng; Gong, Jian; Guo, Bin; Li, Mingzhu; Xu, Hao

2015-01-01

Purpose The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene. Methods A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and 99mTc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6–24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting. Results 131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated 99mTc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins. Conclusions The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC. PMID:25615643

Rhenium and technetium complexes that bind to amyloid-β plaques.

PubMed

Hayne, David J; North, Andrea J; Fodero-Tavoletti, Michelle; White, Jonathan M; Hung, Lin W; Rigopoulos, Angela; McLean, Catriona A; Adlard, Paul A; Ackermann, Uwe; Tochon-Danguy, Henri; Villemagne, Victor L; Barnham, Kevin J; Donnelly, Paul S

2015-03-21

Alzheimer's disease is associated with the presence of insoluble protein deposits in the brain called amyloid plaques. The major constituent of these deposits is aggregated amyloid-β peptide. Technetium-99m complexes that bind to amyloid-β plaques could provide important diagnostic information on amyloid-β plaque burden using Single Photon Emission Computed Tomography (SPECT). Tridentate ligands with a stilbene functional group were used to form complexes with the fac-[M(I)(CO)3](+) (M = Re or (99m)Tc) core. The rhenium carbonyl complexes with tridentate co-ligands that included a stilbene functional group and a dimethylamino substituent bound to amyloid-β present in human frontal cortex brain tissue from subjects with Alzheimer's disease. This chemistry was extended to make the analogous [(99m)Tc(I)(CO)3](+) complexes and the complexes were sufficiently stable in human serum. Whilst the lipophilicity (log D7.4) of the technetium complexes appeared ideally suited for penetration of the blood-brain barrier, preliminary biodistribution studies in an AD mouse model (APP/PS1) revealed relatively low brain uptake (0.24% ID g(-1) at 2 min post injection).

Medullary thyroid cancer: the functions of raf-1 and human achaete-scute homologue-1.

PubMed

Chen, Herbert; Kunnimalaiyaan, Muthusamy; Van Gompel, Jamie J

2005-06-01

Medullary thyroid cancer (MTC) is a prototypic neuroendocrine tumor of the thyroid C cells. Other than surgery, there are no curative therapies for MTC. In this review, we detail recent studies that suggest that targeting specific signaling pathways may be a viable strategy to control MTC tumor progression. Specifically, we discuss the role of the raf-1 and achaete-scute homologue-1 pathways in the MTC tumor growth and differentiation.

Quantitatively accurate activity measurements with a dedicated cardiac SPECT camera: Physical phantom experiments

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

Pourmoghaddas, Amir, E-mail: apour@ottawaheart.ca; Wells, R. Glenn

Purpose: Recently, there has been increased interest in dedicated cardiac single photon emission computed tomography (SPECT) scanners with pinhole collimation and improved detector technology due to their improved count sensitivity and resolution over traditional parallel-hole cameras. With traditional cameras, energy-based approaches are often used in the clinic for scatter compensation because they are fast and easily implemented. Some of the cardiac cameras use cadmium-zinc-telluride (CZT) detectors which can complicate the use of energy-based scatter correction (SC) due to the low-energy tail—an increased number of unscattered photons detected with reduced energy. Modified energy-based scatter correction methods can be implemented, but theirmore » level of accuracy is unclear. In this study, the authors validated by physical phantom experiments the quantitative accuracy and reproducibility of easily implemented correction techniques applied to {sup 99m}Tc myocardial imaging with a CZT-detector-based gamma camera with multiple heads, each with a single-pinhole collimator. Methods: Activity in the cardiac compartment of an Anthropomorphic Torso phantom (Data Spectrum Corporation) was measured through 15 {sup 99m}Tc-SPECT acquisitions. The ratio of activity concentrations in organ compartments resembled a clinical {sup 99m}Tc-sestamibi scan and was kept consistent across all experiments (1.2:1 heart to liver and 1.5:1 heart to lung). Two background activity levels were considered: no activity (cold) and an activity concentration 1/10th of the heart (hot). A plastic “lesion” was placed inside of the septal wall of the myocardial insert to simulate the presence of a region without tracer uptake and contrast in this lesion was calculated for all images. The true net activity in each compartment was measured with a dose calibrator (CRC-25R, Capintec, Inc.). A 10 min SPECT image was acquired using a dedicated cardiac camera with CZT detectors (Discovery NM530c, GE Healthcare), followed by a CT scan for attenuation correction (AC). For each experiment, separate images were created including reconstruction with no corrections (NC), with AC, with attenuation and dual-energy window (DEW) scatter correction (ACSC), with attenuation and partial volume correction (PVC) applied (ACPVC), and with attenuation, scatter, and PVC applied (ACSCPVC). The DEW SC method used was modified to account for the presence of the low-energy tail. Results: T-tests showed that the mean error in absolute activity measurement was reduced significantly for AC and ACSC compared to NC for both (hot and cold) datasets (p < 0.001) and that ACSC, ACPVC, and ACSCPVC show significant reductions in mean differences compared to AC (p ≤ 0.001) without increasing the uncertainty (p > 0.4). The effect of SC and PVC was significant in reducing errors over AC in both datasets (p < 0.001 and p < 0.01, respectively), resulting in a mean error of 5% ± 4%. Conclusions: Quantitative measurements of cardiac {sup 99m}Tc activity are achievable using attenuation and scatter corrections, with the authors’ dedicated cardiac SPECT camera. Partial volume corrections offer improvements in measurement accuracy in AC images and ACSC images with elevated background activity; however, these improvements are not significant in ACSC images with low background activity.« less

Multimodal molecular imaging reveals high target uptake and specificity of 111In and 68Ga labeled fibrin-binding probes for thrombus detection in rats

PubMed Central

Oliveira, Bruno L.; Blasi, Francesco; Rietz, Tyson A.; Rotile, Nicholas J.; Day, Helen; Caravan, Peter

2016-01-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Methods Radiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA) or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging. Results All three radiotracers showed similar affinity to soluble fibrin fragment DD(E) (Ki = 0.53–0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0 ± 0.2% ID/g) with low off-target accumulation. Both radiotracers underwent fast systemic elimination (t1/2 = 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation and/or degradation. Triple isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. Conclusion 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity, and represent useful PET and SPECT probes for thrombus detection. PMID:26251420

Functional discrepancy between two liver lobes after hemilobe biliary drainage in patients with jaundice and bile duct cancer: an appraisal using (99m)Tc-GSA SPECT/CT fusion imaging.

PubMed

Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Noda, Yoshihiro; Hata, Yasuhiro; Murata, Yoriko; Kozuki, Akihito; Tokumaru, Teppei; Nakamura, Toshio; Uka, Kiminori

2014-11-01

To determine the functional discrepancy between the two liver lobes using technetium 99m ((99m)Tc) diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ( GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ) single photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging following preoperative biliary drainage and portal vein embolization ( PVE portal vein embolization ) in patients with jaundice who have bile duct cancer ( BDC bile duct cancer ). This retrospective study was approved by the institutional review board, with waiver of informed consent. Preoperative (99m)Tc- GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin SPECT/CT fusion images from 32 patients with extrahepatic BDC bile duct cancer were retrospectively reviewed. Patients were classified into four groups according to the extent of biliary drainage and presence of a preoperative right PVE portal vein embolization : right lobe drainage group (right drainage), bilateral lobe drainage group (bilateral drainage), left lobe drainage group (left drainage), and left lobe drainage with right PVE portal vein embolization group (left drainage with right PVE portal vein embolization ). Percentage volume and percentage function were measured in each lobe using fusion imaging. The ratio between percentage function and percentage volume (the function-to-volume ratio) was calculated for each lobe, and the results were compared among the four groups. Statistical analysis was performed with Wilcoxon signed-rank tests and Mann-Whitney U tests. The median values for the function-to-volume ratio in the right drainage, bilateral drainage, left drainage, and left drainage with right PVE portal vein embolization group were 1.12, 1.05, 1.02, and 0.81 in the right lobe; and 0.51, 0.88, 0.96, and 1.17 in the left lobe. Significant differences in the function-to-volume ratio were observed among the four groups (right drainage vs bilateral drainage vs left drainage vs left drainage with right PVE portal vein embolization ; with P < .002, P = .023, and P < .002 for the right lobe and P < .001, P = .023, and P < .002 for the left lobe). Hepatic lobar function significantly differs between the two lobes, depending on the extent of biliary drainage and the presence of portal vein embolization.

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.

Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Against Medullary Thyroid Cancer?

PubMed

Damaskos, Christos; Garmpis, Nikolaos; Valsami, Serena; Spartalis, Eleftherios; Antoniou, Efstathios A; Tomos, Periklis; Karamaroudis, Stefanos; Zoumpou, Theofano; Pergialiotis, Vasilios; Stergios, Konstantinos; Michaelides, Constantinos; Kontzoglou, Konstantinos; Perrea, Despina; Nikiteas, Nikolaos; Dimitroulis, Dimitrios

2016-10-01

Medullary thyroid cancer (MTC) is highly malignant, metastatic and recurrent, remaining generally incurable, and responsible for approximately 14% of all thyroid carcinoma-related deaths. MTC can metastasize to lymph nodes, trachea and distant organs, such as brain, lungs, liver and bones. MTC cells are resistant to chemotherapy and traditional external therapies are not showing definite clinical benefits. Scientists are trying to understand the molecular background of carcinogenesis and histone deacetylase (HDAC) seems to play a potential role to gene transcription. On the other hand, HDAC inhibitors (HDACI) hamper the HDAC action giving promising results as new anticancer drugs. The purpose of this review was to evaluate the current status of research considering the role of HDACIs in MTC treatment and to present the latest trends in MTC treatment protocols. This literature review was accomplished using the MEDLINE database. The key words/phrases were; HDACI, medullary thyroid cancer, HDACI in the therapy of neuroendocrine tumors, HDACI in MTC. Forty-one articles were selected from the total number of the search's results. Only sixteen papers focus on the use of HDACIs in the treatment of MTC. In order to extract our conclusions, we took into account some studies whose main topic does not strictly refer to the MTC but they contain noteworthy and useful information. Only English articles published up to August 2016 were assessed and used for writing this review. Molecules, such as valproid acid (VPA), vorinostat, suberoyl bis-hydroxamic acid (SBHA), depsipeptide, belinostat, m-carboxycinnamic acid bis-hydroxamine (CBHA) and AB3 have shown promising antitumor effects against MTC. HDACIs represent a promising field for targeted therapy both for its anticancer properties, as well as for augmenting radiotherapeutic modalities. More trials are needed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Radiopharmaceutical development of a freeze-dried kit formulation for the preparation of [99mTc-EDDA-HYNIC-D-Phe1, Tyr3]-octreotide, a somatostatin analog for tumor diagnosis.

PubMed

Guggenberg, Elisabeth Von; Mikolajczak, Renata; Janota, Barbara; Riccabona, Georg; Decristoforo, Clemens

2004-10-01

[(99m)Tc-EDDA-HYNIC-D-Phe(1),Tyr(3)]-Octreotide ((99m)Tc-EDDA/HYNIC-TOC) is a promising new radiopharmaceutical with the potential to replace [(111)In-DTPA-D-Phe(1)]-Octreotide ((111)In-DTPA-OCT) as the radiopharmaceutical for somatostatin receptor scintigraphy due to the advantage of improved image quality, lower radiation dose for the patient, and daily availability. Here we describe the development of a freeze-dried kit formulation based on the Tricine/EDDA exchange labeling approach for the preparation of this radiopharmaceutical in a clinical setting. Three parameters were of major importance to achieve a suitable formulation with a radiochemical purity (RCP) >90%: addition of bulking agent, the pH of the freeze-drying solution, and the content of stannous chloride. The final formulation consisted of 20 mg Tricine, 10 mg EDDA, 50 mg Mannitol, 20 microg SnCl(2). 2H(2)O, and 20 microg [HYNIC-D-Phe(1), Tyr(3)]-Octreotide (HYNIC-TOC). Radiolabeling was performed by addition of 0.2 M Na(2)HPO(4) to adjust the pH to 6-7, followed by 0.5-2 GBq (99m)Tc sodium pertechnetate, in a total volume of 2 mL and incubation for 10 min in a boiling water bath. Mean RCP values of 10 batches showed values >90% over a storage period of up to 1 year, a high stability up to 24 h of the final preparation, and retained biological activity. The developed kit formulation forms the basis for further clinical evaluation of this promising new radiopharmaceutical. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Improving core surgical training in a major trauma centre.

PubMed

Morris, Daniel L J; Bryson, David J; Ollivere, Ben J; Forward, Daren P

2016-06-01

English Major Trauma Centres (MTCs) were established in April 2012. Increased case volume and complexity has influenced trauma and orthopaedic (T&O) core surgical training in these centres. To determine if T&O core surgical training in MTCs meets Joint Committee on Surgical Training (JCST) quality indicators including performance of T&O operative procedures and consultant supervised session attendance. An audit cycle assessing the impact of a weekly departmental core surgical trainee rota. The rota included allocated timetabled sessions that optimised clinical and surgical learning opportunities. Intercollegiate Surgical Curriculum Programme (ISCP) records for T&O core surgical trainees at a single MTC were analysed for 8 months pre and post rota introduction. Outcome measures were electronic surgical logbook evidence of leading T&O operative procedures and consultant validated work-based assessments (WBAs). Nine core surgical trainees completed a 4 month MTC placement pre and post introduction of the core surgical trainee rota. Introduction of core surgical trainee rota significantly increased the mean number of T&O operative procedures led by a core surgical trainee during a 4 month MTC placement from 20.2 to 34.0 (p<0.05). The mean number of hip hemiarthroplasty procedures led by a core surgical trainee during a 4 month MTC placement was significantly increased (0.3 vs 2.4 [p=0.04]). Those of dynamic hip screw fixation (2.3 vs 3.6) and ankle fracture fixation (0.7 vs 1.6) were not. Introduction of a core surgical trainee rota significantly increased the mean number of consultant validated WBAs completed by a core surgical trainee during a 4 month MTC placement from 1.7 to 6.6 (p<0.0001). Introduction of a departmental core surgical trainee rota utilising a 'problem-based' model can significantly improve T&O core surgical training in MTCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight

PubMed Central

Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels. PMID:28817602

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

PubMed

Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

Glomus Tumor of the Neck Detected With 99mTc EDDA HYNIC-TOC.

PubMed

Girotto, Neva; Bogović-Crnčić, Tatjana; Grbac-Ivanković, Svjetlana; Valković-Zujić, Petra

2017-10-01

A 54-year-old woman was referred to thyroid evaluation because of a lump on the left side of the neck. Ultrasound exam did not show any thyroid abnormality, but highly perfused nodule at the left common carotid artery bifurcation was found. Because of the specific location, somatostatin receptor scintigraphy with Tc EDDA HYNIC-TOC was performed, starting with perfusion images and followed with SPECT/CT imaging at 2 and 4 hours. Well-perfused nodule with intensive accumulation and no other visible pathology in the body raised suspicion of a glomus tumor, consistent with MR exam performed later. Subsequent surgical removal confirmed carotid paraganglioma.

99mTc Sestamibi Thyroid Scan in Amiodarone-Induced Thyrotoxicosis Type I.

PubMed

Patel, Niraj R; Tamara, Luis A; Lee, Ho

2016-07-01

Amiodarone-induced thyrotoxicosis (AIT) type I describes inducement of clinical hyperthyroidism by excessive thyroidal iodine in the setting of latent Graves disease, and therapy differs from that used for AIT type II. A 65-year-old man previously on amiodarone for atrial fibrillation developed clinical hyperthyroidism. Diagnosis of AIT was made, but the type was not clear. Tc sestamibi thyroid scan showed diffusely increased uptake and retention in an enlarged thyroid gland, a pattern consistent with AIT type I. Methimazole was initiated and controlled the thyrotoxicosis. I iodide thyroid scan and uptake study performed later was consistent with Graves disease.

Absent Cerebellar Circulation With Intact Cerebral Blood Flow on a 99mTc Bicisate "Brain Death" Study.

PubMed

Schmidt, Matthew Q; Schraml, Frank V

2017-12-01

A 55-year old woman presented in an obtunded state and was found to have a subarachnoid hemorrhage. After endovascular repair, her condition deteriorated, and brain death was suspected. A Tc bicisate brain blood flow study was performed, which showed a complete absence of blood flow to the cerebellum despite intact circulation to the cerebral hemispheres. These atypical findings are likely a result of a transient intracranial pressure differential and the timing of the study. A timely and accurate declaration of brain death has important psychosocial and ethical implications, particularly when organ donation is being considered.

Influence of Decontaminating Agents and Swipe Materials on Laboratory Simulated Working Surfaces Wet Spilled with Sodium Pertechnetate

PubMed Central

Akchata, Suman; Lavanya, K; Shivanand, Bhushan

2017-01-01

Context: Decontamination of various working surfaces with sodium pertechnetate minor spillage is essential for maintaining good radiation safety practices as well as for regulatory compliance. Aim: To observe the influences of decontaminating agents and swipe materials on different type of surfaces used in nuclear medicine laboratory work area wet spilled with 99m-technetium (99mTc) sodium pertechnetate. Settings and Design: Lab-simulated working surface materials. Experimental study design. Materials and Methods: Direct decontamination method on dust-free lab simulated new working surfaces [stainless steel, polyvinyl chloride (PVC), Perspex, resin] using four decontaminating agents [tap water, soap water (SW), Radiacwash, and spirit] with four different swipe material [cotton, tissue paper (TP), Whatman paper (WP), adsorbent sheet (AS)] was taken 10 samples (n = 10) for each group. Statistical Analysis: Parametric test two-way analysis of variance is used with significance level of 0.005, was used to evaluate statistical differences between different group of decontaminating agent and swipe material, and the results are expressed in mean ± SD. Results: Decontamination factor is calculated after five cleaning for each group. A total of 160 samples result calculated using four decontaminating agent (tap water, SW, Radiacwash, and spirit), four swipe material (cotton, TP, WP, and AS) for commonly used surface (stainless steel, PVC, Perspex, resin) using direct method by 10 samples (n = 10) for each group. Conclusions: Tap water is the best decontaminating agent compared with SW, Radiac wash and spirit for the laboratory simulated stainless steel, PVC, and Perspex surface material, whereas in case of resin surface material, SW decontaminating agent is showing better effectiveness. Cotton is the best swipe material compared to WP-1, AS and TP for the stainless steel, PVC, Perspex, and resin laboratory simulated surface materials. Perspex and stainless steel are the most suitable and recommended laboratory surface material compared to PVC and resin in nuclear medicine. Radiacwash may show better result for 99mTc labelled product and other radionuclide contamination on the laboratory working surface area. PMID:28680198

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

Walker, Katherine L.; Judenhofer, Martin S.; Cherry, Simon R.

In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. Furthermore, such high-resolution systems have relatively poor sensitivity (typically 0.01% to 0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatialmore » resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO 4- xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. In conclusion, UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.« less

Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

PubMed

Vyas, Tushar K; Babbar, A K; Sharma, R K; Singh, Shashi; Misra, Ambikanandan

2006-03-01

The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more rapid and larger extent of transport of clonazepam into the rat brain with intranasal CMME, which may prove useful in treating acute status epileptics. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

PubMed Central

Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2011-01-01

ABSTRACT Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract. PMID:21552677

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.

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.

Management of hip fractures pre- and post-Major Trauma Centre activation.

PubMed

Wong, Ken; Rich, James; Yip, Grace; Loizou, Constantinos; Hull, Peter

2015-10-01

In April 2012, the activation of the regional trauma networks in England was carried out to improve the organisation of trauma care. NHS Trusts that could meet the highest standard of care to complex trauma were designated Major Trauma Centres (MTCs). MTCs receive patients fulfilling certain triage criteria, as well as secondary transfers from nearby trauma units. While complex trauma care is streamlined with this new organisation, the impact this would have on the rest of the trauma workload within MTCs as well as non-MTC hospitals is uncertain. We investigate whether the management of hip fracture cases had suffered as a result of a trauma unit becoming a MTC. Summary data was collated from the National Hip Fracture Database website for the periods of April 2011-April 2012 (the 'pre-MTC' activation period) and April 2012-April 2013 (the 'post-MTC' activation period). As our primary outcome, we compared the time to surgery within 36h between MTCs and non-MTCs for the periods detailed above. Other outcome measures were: reasons for delay to surgery, length of acute stay, proportion of cases meeting Best Practice Tariff criteria. A total of 54,897 and 55,998 fNOF patients were included for all hospitals in England in the pre- and post-MTC periods respectively. For MTCs, a weighted mean average of 66.6% patients had surgery within 36h in the pre-MTC period versus 71.4% of patients in the post MTC period (p<0.0001). For non-MTCs, a weighted mean average of 70.0% of patients had surgery within 36h in the pre-MTC period versus 73.8% of patients in the post-MTC period (p<0.0001). Non-MTCs in both pre- and post-MTC activation periods were therefore better in percentage of patients receiving surgery within 36h. The data presented suggests that the creation of MTCs has not had a deleterious effect on the management of hip fracture patients. This paper aims to stimulate the important discussion of maintaining a consistently improving standard throughout the spectrum of trauma care, in conjunction with the development of regional Major Trauma Networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

A travelling standard for radiopharmaceutical production centres in Italy

NASA Astrophysics Data System (ADS)

Capogni, M.; de Felice, P.; Fazio, A.

Short-lived radionuclides, γ, β+ and/or β- emitters, such as 18F, and 99mTc, particularly useful for nuclear medicine applications, both diagnostic and in radiotherapy, can be produced with high-specific activity in a small biomedical cyclotron or by a radionuclide generator. While [18F]Fludeoxyglucose ([18F]FDG) is a widely used radiopharmaceutical for positron emission tomography, the development of innovative diagnostic techniques and therapies involves the use of new radio-labelled molecules and emerging radionuclides, such as 64Cu and 124I. During the last 3 years, an extensive supply of [18F]FDG was started by many production sites in Italy, and new radiopharmaceuticals are being studied for future nuclear medical applications. Therefore, a special nuclear medicine research programme for primary standard development and transferral to the end-users has been carried out by the ENEA-INMRI. Because of the short half-lives of these nuclides, a portable well-type ionisation chamber was established as a secondary travelling standard. This device has been calibrated and transported to the radiopharmaceutical production centres in Italy where the local instrumentation, typically radionuclide calibrators, has been calibrated by a simple comparison, with an uncertainty level lower than 2%.

Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.

PubMed

Wang, Xuejuan; Yang, Zhi; Lin, Baohe; Zhang, Yan; Zhai, Shizhen; Zhao, Qichao; Xie, Qing; Liu, Fei; Han, Xuedi; Li, Jinfeng; Ouyang, Tao

2016-06-21

We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection. 99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection. The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively. 99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

PubMed

Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2016-01-01

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

On-resonance Variable Delay Multi Pulse Scheme for Imaging of Fast-exchanging Protons and semi-solid Macromolecules

PubMed Central

Xu, Jiadi; Chan, Kannie W.Y.; Xu, Xiang; Yadav, Nibhay; Liu, Guanshu; van Zijl, Peter C. M.

2016-01-01

Purpose To develop an on-resonance variable delay multi-pulse (VDMP) scheme to image magnetization transfer contrast (MTC) as well as the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above about 1 kHz. Methods A train of high power binomial pulses was applied at the water resonance. The inter-pulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions due to their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. Results Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA) and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method showing strong gray/white matter contrast for the slowly transferring MTC protons while the TFP map was more uniform across the brain but somewhat higher in gray matter. Conclusions The new method provides a simple way of imaging fast-exchanging protons, as well as MTC components with a slow transfer rate. PMID:26900759

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.

Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation.

PubMed

Feldman, G L; Edmonds, M W; Ainsworth, P J; Schuffenecker, I; Lenoir, G M; Saxe, A W; Talpos, G B; Roberson, J; Petrucelli, N; Jackson, C E

2000-07-01

Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

PubMed

Rosario, P W; Calsolari, M R

2017-02-01

This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctn<47 pg/ml and stimulated Ctn<655.2 pg/ml. Among patients with basal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium. © Georg Thieme Verlag KG Stuttgart · New York.

Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study.

PubMed

Mathiesen, Jes Sloth; Habra, Mouhammed Amir; Bassett, John Howard Duncan; Choudhury, Sirazum Mubin; Balasubramanian, Sabapathy Prakash; Howlett, Trevor A; Robinson, Bruce G; Gimenez-Roqueplo, Anne-Paule; Castinetti, Frederic; Vestergaard, Peter; Frank-Raue, Karin

2017-06-01

The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Retrospective analysis. International collaboration. Included were 13 A883F carriers. The intervention was thyroidectomy. Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level. Copyright © 2017 Endocrine Society

A Prestressed Cable Network Model of the Adherent Cell Cytoskeleton

PubMed Central

Coughlin, Mark F.; Stamenović, Dimitrije

2003-01-01

A prestressed cable network is used to model the deformability of the adherent cell actin cytoskeleton. The overall and microstructural model geometries and cable mechanical properties were assigned values based on observations from living cells and mechanical measurements on isolated actin filaments, respectively. The models were deformed to mimic cell poking (CP), magnetic twisting cytometry (MTC) and magnetic bead microrheometry (MBM) measurements on living adherent cells. The models qualitatively and quantitatively captured the fibroblast cell response to the deformation imposed by CP while exhibiting only some qualitative features of the cell response to MTC and MBM. The model for CP revealed that the tensed peripheral actin filaments provide the key resistance to indentation. The actin filament tension that provides mechanical integrity to the network was estimated at ∼158 pN, and the nonlinear mechanical response during CP originates from filament kinematics. The MTC and MBM simulations revealed that the model is incomplete, however, these simulations show cable tension as a key determinant of the model response. PMID:12547813

A prestressed cable network model of the adherent cell cytoskeleton.

PubMed

Coughlin, Mark F; Stamenović, Dimitrije

2003-02-01

A prestressed cable network is used to model the deformability of the adherent cell actin cytoskeleton. The overall and microstructural model geometries and cable mechanical properties were assigned values based on observations from living cells and mechanical measurements on isolated actin filaments, respectively. The models were deformed to mimic cell poking (CP), magnetic twisting cytometry (MTC) and magnetic bead microrheometry (MBM) measurements on living adherent cells. The models qualitatively and quantitatively captured the fibroblast cell response to the deformation imposed by CP while exhibiting only some qualitative features of the cell response to MTC and MBM. The model for CP revealed that the tensed peripheral actin filaments provide the key resistance to indentation. The actin filament tension that provides mechanical integrity to the network was estimated at approximately 158 pN, and the nonlinear mechanical response during CP originates from filament kinematics. The MTC and MBM simulations revealed that the model is incomplete, however, these simulations show cable tension as a key determinant of the model response.

67 FR 24495 - United States v. Microsoft Corporation; Public Comments; Notice (MTC-00003461 - MTC-00007629)

Federal Register 2010, 2011, 2012, 2013, 2014

2002-05-03

... (web-serving software), Linux, Perl, and those who are building a compatible & free version of MS`s..., Argument from Design Argument from Design-Web & Multimedia [email protected] http://www.ardes.com MTC-00003464... organization could be a good target for this effort. Their web address is http:// www.gnu.org/. This effort...

The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells.

PubMed

Vitagliano, Donata; De Falco, Valentina; Tamburrino, Anna; Coluzzi, Sabrina; Troncone, Giancarlo; Chiappetta, Gennaro; Ciardiello, Fortunato; Tortora, Giampaolo; Fagin, James A; Ryan, Anderson J; Carlomagno, Francesca; Santoro, Massimo

2011-02-01

Oncogenic conversion of the RET tyrosine kinase is a frequent feature of medullary thyroid carcinoma (MTC). ZD6474 (vandetanib) is an ATP-competitive inhibitor of RET, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptors kinases. In this study, we have studied ZD6474 mechanism of action in TT and MZ-CRC-1 human MTC cell lines, carrying cysteine 634 to tryptophan (C634W) and methionine 918 to threonine (M918T) RET mutation respectively. ZD6474 blunted MTC cell proliferation and RET, Shc and p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation. Single receptor knockdown by RNA interference showed that MTC cells depended on RET for proliferation. Adoptive expression of the ZD6474-resistant V804M RET mutant rescued proliferation of TT cells under ZD6474 treatment, showing that RET is a key ZD6474 target in these MTC cells. Upon RET inhibition, adoptive stimulation of EGFR partially rescued TT cell proliferation, MAPK signaling, and expression of cell-cycle-related genes. This suggests that simultaneous inhibition of RET and EGFR by ZD6474 may overcome the risk of MTC cells to escape from RET blockade through compensatory over-activation of EGFR.

Surgical strategy for the treatment of sporadic medullary thyroid carcinoma: our experience.

PubMed

Lupone, G; Antonino, A; Rosato, A; Zenone, P; Iervolino, E M; Grillo, M; De Palma, M

2012-01-01

Medullary thyroid carcinoma (MTC) is a rare disease which accounts for approximately 5-9% of all thyroid cancers and originates from the calcitonin-screening parafollicular C cells. MTC can be divided into two subgroups: sporadic (75%) or inherited (25%). The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. The purpose of the study is to review our single institution's experience with MTC since 1998 and to evaluate surgical strategy, patterns of lymph node metastases and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent sporadic medullary thyroid carcinoma. A retrospective review of 26 patients treated for MTC at the "Antonio Cardarelli" Hospital referral center, in Naples, between 1998 and 2012. There were 18 female and 8 male patients, median age at presentation was 55 years, and median follow-up for survivors was 5 years. Total thyroidectomy was performed in all 26 patients; central compartment (CC) node dissection (level VI) in 12 (46%) patients; central plus lateral compartment (LC) node dissection (levels II, III, and IV) in 7 (27%) patients. 4 patients (15%) underwent reoperation for loco-regional recurrent/persistent MTC. Results. After a median post-surgical follow-up of 5 years (range 1-10 years), 63 % of patients were living disease-free, 15% were living with disease and/or persistently elevated calcitonin levels after surgery, 11% were deceased due to MTC and 11 % were lost to follow-up. We agree with most authors advocating for a total thyroidectomy and prophylactic central neck dissection in the setting of clinically detected MTC. Lateral neck dissection may be best reserved for patients with positive preoperative imaging. Nevertheless MTC has a high rate of lymph node metastases that are sub optimally detected preoperatively in the central compartment by neck ultrasound or intra-operatively by the surgeon, and reoperation is associated with a higher rate of surgical complications. In our limited experience, patients with thyroid confined nodular pathology, without nodal disease and unknown preoperative diagnosis of MTC, underwent only total thyroidectomy with a good prognosis.

The Perceived Relationship Among Personnel Readiness, Job Performance and Work Demands: A Case for Physical Ability Testing

DTIC Science & Technology

2012-09-01

under fire (MANUF) (DoN, 2008a). The MTC is an 880 yard sprint (DoN, 2008a). Figure 2 illustrates the layout of MANUF. The AL is a continuous...00-8:59 0 9:00-9:59 0 10:00-10:59 0 11:00-11:59 0 12:00-12:59 0 13:00+ 0 I don’t remember my time *54. Select your 450 meter swim time. (Time...55. Select your calorie(s) burned on the elliptical machine. O G-99 0 100-199 0 200-299 0 300-399 0 400 + 0 I don’t remember 73 An Examination

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.

Wild boar tuberculosis in Iberian Atlantic Spain: a different picture from Mediterranean habitats

PubMed Central

2013-01-01

Background Infections with Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex (MTC) are shared between livestock, wildlife and sporadically human beings. Wildlife reservoirs exist worldwide and can interfere with bovine tuberculosis (TB) eradication efforts. The Eurasian wild boar (Sus scrofa) is a MTC maintenance host in Mediterranean Iberia (Spain and Portugal). However, few systematic studies in wild boar have been carried out in Atlantic regions. We describe the prevalence, distribution, pathology and epidemiology of MTC and other mycobacteria from wild boar in Atlantic Spain. A total of 2,067 wild boar were sampled between 2008 and 2012. Results The results provide insight into the current status of wild boar as MTC and Mycobacterium avium complex (MAC) hosts in temperate regions of continental Europe. The main findings were a low TB prevalence (2.6%), a low proportion of MTC infected wild boar displaying generalized TB lesions (16.7%), and a higher proportion of MAC infections (4.5%). Molecular typing revealed epidemiological links between wild boar and domestic – cattle, sheep and goat – and other wildlife – Eurasian badger (Meles meles) and red fox (Vulpes vulpes) – hosts. Conclusions This study shows that the likelihood of MTC excretion by wild boar in Atlantic habitats is much lower than in Mediterranean areas. However, wild boar provide a good indicator of MTC circulation and, given the current re-emergence of animal TB, similar large-scale surveys would be advisable in other Atlantic regions of continental Europe. PMID:24010539

Novel Multiplex Real-Time PCR Diagnostic Assay for Identification and Differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis Complex Strains▿†

PubMed Central

Reddington, Kate; O'Grady, Justin; Dorai-Raj, Siobhan; Maher, Majella; van Soolingen, Dick; Barry, Thomas

2011-01-01

Tuberculosis (TB) in humans is caused by members of the Mycobacterium tuberculosis complex (MTC). Rapid detection of the MTC is necessary for the timely initiation of antibiotic treatment, while differentiation between members of the complex may be important to guide the appropriate antibiotic treatment and provide epidemiological information. In this study, a multiplex real-time PCR diagnostics assay using novel molecular targets was designed to identify the MTC while simultaneously differentiating between M. tuberculosis and M. canettii. The lepA gene was targeted for the detection of members of the MTC, the wbbl1 gene was used for the differentiation of M. tuberculosis and M. canettii from the remainder of the complex, and a unique region of the M. canettii genome, a possible novel region of difference (RD), was targeted for the specific identification of M. canettii. The multiplex real-time PCR assay was tested using 125 bacterial strains (64 MTC isolates, 44 nontuberculosis mycobacteria [NTM], and 17 other bacteria). The assay was determined to be 100% specific for the mycobacteria tested. Limits of detection of 2.2, 2.17, and 0.73 cell equivalents were determined for M. tuberculosis/M. canettii, the MTC, and M. canettii, respectively, using probit regression analysis. Further validation of this diagnostics assay, using clinical samples, should demonstrate its potential for the rapid, accurate, and sensitive diagnosis of TB caused by M. tuberculosis, M. canettii, and the other members of the MTC. PMID:21123525

On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules.

PubMed

Xu, Jiadi; Chan, Kannie W Y; Xu, Xiang; Yadav, Nirbhay; Liu, Guanshu; van Zijl, Peter C M

2017-02-01

To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T 2 components in MTC and separated out using a variable mixing time. Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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.

A sensitive and rapid radiolabelling method for the in vivo pharmacokinetic study of lentinan.

PubMed

Zhang, Yu; Zheng, Ziming; Yang, Xiawen; Pan, Xianglin; Yin, Lianglan; Huang, Xiao; Li, Qiang; Shu, Yamin; Zhang, Qilin; Wang, Kaiping

2018-06-20

The aim of this study is to establish a rapid and sensitive method for detecting lentinan (LNT) in biosamples and to evaluate the pharmacokinetics of LNT in mice and rats. A diethylenetriaminepentaacetic acid (DTPA) derivative of LNT (DTPA-LNT) was synthesized first to allow labelling with 99m-technetium (99mTc). After purification and identification, 99mTc-DTPA-LNT was intravenously administered to mice (2 mg kg-1) and rats at different doses (0.5, 2 and 8 mg kg-1). The results showed that the 99mTc-labelling method was suitable for the quantification of the LNT concentration in biological samples, with satisfactory linearity (r2 > 0.998), precision (<7%), accuracy (95.01-104.51%) and total recovery (∼90%). The blood concentration-time profiles of 99mTc-DTPA-LNT were consistent with the two-compartment model and showed a rapid distribution phase and a slow elimination, and no significant difference in the blood level of LNT was found among the tested doses (0.5, 2 and 8 mg kg-1). LNT was predominantly incorporated into the liver and spleen, and there was a small amount of aggregation in the bile, kidneys, lungs and stomach. Approximately 40% of the administered radioactivity was detected in urine and faeces within 24 h post-dosing. In addition, SPECT imaging of 99mTc-DTPA-LNT was performed to visually reveal the pharmacokinetic characteristics of LNT. These findings provide a reference for further study and for use of LNT and other β-glucans.

Developing and Testing a Scale of Moral Thinking and Communication (MTC) Functioning: A Preliminary Study and Its Implications for Moral Development and Education

ERIC Educational Resources Information Center

Lee, Chi-Ming Angela; Thoma, Stephen J.

2018-01-01

The purpose of this study was to develop and test a scale assessing students' moral thinking and communication (MTC) functioning as well as to explore the implications for moral development and education. The rationale of MTC functioning, including interaction of four independent competencies: moral awareness, moral judgement, moral discourse, and…

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.

Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of 111In- and 68Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats.

PubMed

Oliveira, Bruno L; Blasi, Francesco; Rietz, Tyson A; Rotile, Nicholas J; Day, Helen; Caravan, Peter

2015-10-01

We recently showed the high target specificity and favorable imaging properties of 64Cu and Al18F PET probes for noninvasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with 68Ga, 111In, or 99mTc as thrombus imaging agents for PET and SPECT. In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in 2 animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging. Radiotracers were synthesized using a known fibrin-binding peptide conjugated to 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DOTA-MA), or a diethylenetriamine ligand (DETA-propanoic acid [PA]), followed by labeling with 68Ga (FBP14, 68Ga-NODAGA), 111In (FBP15, 111In-DOTA-MA), or 99mTc (FBP16, 99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics, and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed 125I-labeled thrombi and with a nonbinding control probe using SPECT/PET/CT imaging. All 3 radiotracers showed affinity similar to soluble fibrin fragment DD(E) (inhibition constant=0.53-0.83 μM). After the kidneys, the highest uptake of 68Ga-FBP14 and 111In-FBP15 was in the thrombus (1.0±0.2 percentage injected dose per gram), with low off-target accumulation. Both radiotracers underwent fast systemic elimination (half-life, 8-15 min) through the kidneys, which led to highly conspicuous thrombi on PET and SPECT images. 99mTc-FBP16 displayed low target uptake and distribution consistent with aggregation or degradation. Triple-isotope imaging experiments showed that both 68Ga-FBP14 and 111In-FBP15, but not the nonbinding derivative 64Cu-D-Cys-FBP8, detected the location of the 125I-labeled thrombus, confirming high target specificity. 68Ga-FBP14 and 111In-FBP15 have high fibrin affinity and thrombus specificity and represent useful PET and SPECT probes for thrombus detection. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

High-resolution atmospheric inversion of urban CO2 emissions during the dormant season of the Indianapolis Flux Experiment (INFLUX)

NASA Astrophysics Data System (ADS)

Lauvaux, Thomas; Miles, Natasha L.; Deng, Aijun; Richardson, Scott J.; Cambaliza, Maria O.; Davis, Kenneth J.; Gaudet, Brian; Gurney, Kevin R.; Huang, Jianhua; O'Keefe, Darragh; Song, Yang; Karion, Anna; Oda, Tomohiro; Patarasuk, Risa; Razlivanov, Igor; Sarmiento, Daniel; Shepson, Paul; Sweeney, Colm; Turnbull, Jocelyn; Wu, Kai

2016-05-01

Based on a uniquely dense network of surface towers measuring continuously the atmospheric concentrations of greenhouse gases (GHGs), we developed the first comprehensive monitoring systems of CO2 emissions at high resolution over the city of Indianapolis. The urban inversion evaluated over the 2012-2013 dormant season showed a statistically significant increase of about 20% (from 4.5 to 5.7 MtC ± 0.23 MtC) compared to the Hestia CO2 emission estimate, a state-of-the-art building-level emission product. Spatial structures in prior emission errors, mostly undetermined, appeared to affect the spatial pattern in the inverse solution and the total carbon budget over the entire area by up to 15%, while the inverse solution remains fairly insensitive to the CO2 boundary inflow and to the different prior emissions (i.e., ODIAC). Preceding the surface emission optimization, we improved the atmospheric simulations using a meteorological data assimilation system also informing our Bayesian inversion system through updated observations error variances. Finally, we estimated the uncertainties associated with undetermined parameters using an ensemble of inversions. The total CO2 emissions based on the ensemble mean and quartiles (5.26-5.91 MtC) were statistically different compared to the prior total emissions (4.1 to 4.5 MtC). Considering the relatively small sensitivity to the different parameters, we conclude that atmospheric inversions are potentially able to constrain the carbon budget of the city, assuming sufficient data to measure the inflow of GHG over the city, but additional information on prior emission error structures are required to determine the spatial structures of urban emissions at high resolution.

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.

(99m)Tc-labeled SWL specific peptide for targeting EphA2 receptor.

PubMed

Liu, Yu; Lan, Xiaoli; Wu, Tao; Lang, Juntao; Jin, Xueyan; Sun, Xun; Wen, Qiong; An, Rui

2014-07-01

EphA2, one member of the Eph receptor family, is widely expressed in multiple aggressive cancers. SWL, a small peptide identified by phage display, has high binding affinity to EphA2, suggesting that it could be exploited for targeted molecular imaging. Therefore, a novel peptide-based probe, (99m)Tc-HYNIC-SWL, was developed and its potential to specifically target EphA2-positive tumors was investigated. The SWL peptide was labeled with hydrazinonicotinic acid (HYNIC), followed by (99m)Tc labeling. Immunofluorescence staining was carried out to detect the expression of EphA2 in A549 lung cancer cells and OCM-1 melanoma cells. Saturation binding experiments were performed by incubating A549 cells with increasing concentrations of radiolabeled peptide in vitro. To test the probe in vivo, nude mice bearing either A549 or OCM-1 derived tumors were established, injected with (99m)Tc-HYNIC-SWL, and subjected to SPECT imaging. Mice injected with excess unlabeled SWL were used as a specific control. Ex vivo γ-counting of dissected tissues from the mice was also performed to evaluate biodistribution. Immunofluorescence staining showed that A549 cells intensively expressed EphA2, while OCM-1 cells had little expression. (99m)Tc-HYNIC-SWL displayed high binding affinity with A549 cells (KD=2.6±0.7nM). From the SPECT images and the results of the biodistribution study, significantly higher uptake of the tracer was seen in A549 tumors (1.44±0.12 %ID/g) than in OCM-1 tumors (0.43±0.20 %ID/g) at 1h after injection. Pre-injection with excess unlabeled peptide in A549-bearing nude mice, significantly reduced tumor uptake of the radiolabeled probe (0.58±0.20 %ID/g) was seen. These data suggest that (99m)Tc-HYNIC-SWL specifically targets EphA2 in tumors. The expression of EphA2 can be noninvasively investigated using (99m)Tc-HYNIC-SWL by SPECT imaging. The in vitro and in vivo characteristics of (99m)Tc-HYNIC-SWL make it a promising probe for EphA2-positive tumor imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Apatinib-treated advanced medullary thyroid carcinoma: a case report.

PubMed

Chen, Kan; Gao, Yun; Shi, Fei; Cao, Guangqiang; Bao, Jiandong

2018-01-01

Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor. The patient was treated with thyroid lobectomy but developed MTC with extensive metastasis. The levels of serum calcitonin and carcino-embryonic antigen were much higher than the normal range. Apatinib was given at a dose of 500 mg daily and adjusted according to tolerance. Sixteen weeks following apatinib administration, the patient achieved a partial response, which lasted more than 9 weeks. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of advanced MTC.

Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis.

PubMed

Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

2016-01-01

Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

Wavelet-based multiscale analysis of minimum toe clearance variability in the young and elderly during walking.

PubMed

Khandoker, Ahsan H; Karmakar, Chandan K; Begg, Rezaul K; Palaniswami, Marimuthu

2007-01-01

As humans age or are influenced by pathology of the neuromuscular system, gait patterns are known to adjust, accommodating for reduced function in the balance control system. The aim of this study was to investigate the effectiveness of a wavelet based multiscale analysis of a gait variable [minimum toe clearance (MTC)] in deriving indexes for understanding age-related declines in gait performance and screening of balance impairments in the elderly. MTC during walking on a treadmill for 30 healthy young, 27 healthy elderly and 10 falls risk elderly subjects with a history of tripping falls were analyzed. The MTC signal from each subject was decomposed to eight detailed signals at different wavelet scales by using the discrete wavelet transform. The variances of detailed signals at scales 8 to 1 were calculated. The multiscale exponent (beta) was then estimated from the slope of the variance progression at successive scales. The variance at scale 5 was significantly (p<0.01) different between young and healthy elderly group. Results also suggest that the Beta between scales 1 to 2 are effective for recognizing falls risk gait patterns. Results have implication for quantifying gait dynamics in normal, ageing and pathological conditions. Early detection of gait pattern changes due to ageing and balance impairments using wavelet-based multiscale analysis might provide the opportunity to initiate preemptive measures to be undertaken to avoid injurious falls.

High efficiency microfluidic beta detector for pharmacokinetic studies in small animals

NASA Astrophysics Data System (ADS)

Convert, Laurence; Girard-Baril, Frédérique; Renaudin, Alan; Grondin, Étienne; Jaouad, Abdelatif; Aimez, Vincent; Charette, Paul; Lecomte, Roger

2011-10-01

New radiotracers are continuously being developed to improve diagnostic efficiency using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). The characterization of their pharmacokinetics requires blood radioactivity monitoring over time during the scan and is very challenging in small animals because of the low volume of blood available. In this work, a prototype microfluidic blood counter made of a microchannel atop a silicon substrate containing PIN photodiodes is proposed to improve beta detection efficiency in a small volume by eliminating unnecessary interfaces between fluid and detector. A flat rectangular-shaped epoxy channel, 36 μm×1.26 mm cross section and 31.5 mm in length, was microfabricated over a die containing an array of 2×2 mm 2 PIN photodiodes, leaving only a few micrometers of epoxy floor layer between the fluid and the photodiode sensitive surface. This geometry leads to a quasi 2D source, optimizing geometrical detection efficiency that was estimated at 41% using solid angle calculation. CV- IV measurements were made at each fabrication step to confirm that the microchannel components had no significant effects on the diodes' electrical characteristics. The chip was wire-bonded to a PCB and connected to charge sensitive preamplifier and amplifier modules for pulse shaping. Energy spectra recorded for different isotopes showed continuous beta distribution for PET isotopes and monoenergetic conversion electron peaks for 99mTc. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 26% to 33% for PET tracers ( 18F, 13N, 11C, 68Ga) and more than 2% for 99mTc. Input functions were successfully simulated with 18F, confirming the setup's suitability for pharmacokinetic modeling of PET and SPECT radiotracers in animal experiments. By using standard materials and procedures, the fabrication process is well suited to on-chip microfluidic functionality, allowing full characterization of new radiotracers.