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

Abstract

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 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 {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 andmore » 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

Authors:
; ; ;  [1];  [2]; ; ; ; ;  [3]
  1. Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation)
  2. (Russian Federation)
  3. Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)
Publication Date:
OSTI Identifier:
22608296
Resource Type:
Journal Article
Resource Relation:
Journal Name: AIP Conference Proceedings; Journal Volume: 1760; Journal Issue: 1; Conference: PC'16: International conference on physics of cancer: Interdisciplinary problems and clinical applications 2016, Tomsk (Russian Federation), 22-25 Mar 2016; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANESTHESIA; ANIMAL TISSUES; BIOMEDICAL RADIOGRAPHY; CARCINOMAS; CELL CULTURES; CENTRIFUGATION; CHO CELLS; COMPARATIVE EVALUATIONS; FEMUR; GLUCOSE; LABORATORY ANIMALS; LUNGS; MAMMARY GLANDS; OVARIES; RADIOACTIVITY; RADIOPHARMACEUTICALS; SCINTISCANNING; TECHNETIUM 99; TUMOR CELLS

Citation Formats

Zeltchan, R., E-mail: r.zelchan@yandex.ru, Medvedeva, A., Sinilkin, I., Chernov, V., Tomsk Polytechnic University, Tomsk, 634050, Stasyuk, E., Rogov, A., Il’ina, E., Larionova, L., and Skuridin, V. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose. United States: N. p., 2016. Web. doi:10.1063/1.4960291.
Zeltchan, R., E-mail: r.zelchan@yandex.ru, Medvedeva, A., Sinilkin, I., Chernov, V., Tomsk Polytechnic University, Tomsk, 634050, Stasyuk, E., Rogov, A., Il’ina, E., Larionova, L., & Skuridin, V. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose. United States. doi:10.1063/1.4960291.
Zeltchan, R., E-mail: r.zelchan@yandex.ru, Medvedeva, A., Sinilkin, I., Chernov, V., Tomsk Polytechnic University, Tomsk, 634050, Stasyuk, E., Rogov, A., Il’ina, E., Larionova, L., and Skuridin, V. Tue . "Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose". United States. doi:10.1063/1.4960291.
@article{osti_22608296,
title = {Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose},
author = {Zeltchan, R., E-mail: r.zelchan@yandex.ru and Medvedeva, A. and Sinilkin, I. and Chernov, V. and Tomsk Polytechnic University, Tomsk, 634050 and Stasyuk, E. and Rogov, A. and Il’ina, E. and Larionova, L. and Skuridin, V.},
abstractNote = {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 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 {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.},
doi = {10.1063/1.4960291},
journal = {AIP Conference Proceedings},
number = 1,
volume = 1760,
place = {United States},
year = {Tue Aug 02 00:00:00 EDT 2016},
month = {Tue Aug 02 00:00:00 EDT 2016}
}
  • A comparison of stannous phytate and antimony sulfide colloid, both labeled with Tc-99m, was conducted during the performance of internal mammary lymphoscintigraphy in 46 patients. Thirteen of these patients were randomized to receive both radiotracers in two consecutive studies. The results indicated a statistical difference between agents; Tc-99m antimony sulfide allowed visualization of a greater number of more intense nodes, better delineation of the total length of the internal mammary lymph-node chain, and a more consistent visualization of supraclavicular nodes. Although previously published animal data suggest utility of Tc-99m stannous phytate for lymph-node imaging, Tc-99m antimony sulfide was shown inmore » this clinical comparison to provide a more reliable representation of lymph-node anatomy.« less
  • A series of new ligands and the corresponding technetium-99m chelates based on diamide dimercaptide donor groups were synthesized as derivatives of technetium-99m 1,2-bis(2-thioacetamido)ethane, a complex shown to be excreted by renal tubular secretion. Chelation with 99mTc resulted in single radiochemical products or the expected numbers of stereoisomers. They were purified by high-performance liquid chromatography (HPLC) and evaluated in mice as potential renal tubular function agents. The in vivo properties were sensitive to the presence of functional groups, the positional isomerism of the carboxylate group functionality, and the chelate ring stereochemistry of the ligand. The presence of methyl groups slowed renalmore » transit and decreased renal specificity. Cyclohexyl rings fused to the ethylene bridge of the center chelate ring decreased renal excretion while aromatic rings essentially abolished renal excretion. Slow hepatobiliary clearance was observed as an alternate mode of excretion. Polar groups, such as hydroxyl, carboxylate, and carboxamide, increased renal excretion rates and specificity in a stereochemically dependent manner. 99mTc chelates of 1,3-bis(2-thioacetamido)-2-hydroxypropane, 3,4-bis(2-thioacetamido)butanoate and 1,8-dimercapto-2,7-dioxo-3,6-diazanonanoate were identified as promising new renal radiopharmaceuticals.« less
  • An electrophoretic procedure is outlined for the determination of the number of ligands bound to technetium-99m radiopharmaceuticals. The approach involves use of ligands that will complex technetium in a similar fashion but that differ in charge. This approach was applied experimentally to dimercapto ligands in which the ligating sulfur atoms are separated by a flexible three-carbon chain (1,3-dimercapto compounds). Two such ligands studied are 1,3-dimercaptopropane (DMP) and dihydrothioctic acid (DHTA). The Tc compound of DHTA migrates much farther on electrophoresis than the Tc complex of DMP. However, when TcO/sub 4//sup -/ is reduced by SnCl/sub 2/ or NaBH/sub 4/ inmore » the presence of equimolar quantities of DHTA and DMP, a new compound is formed being twice as abundant as either the TcDMP or the TcDHTA compound and migrating an intermediate distance. The formation of this new complex and the 1:2:1 distribution indicates that two 1,3-dimercapto compounds are attached to the Tc-center in all three compounds.« less
  • Imidodiphosphate (IDP) is an analog of pyrophosphate and diphosphonate, with a P-N-P bond instead of P-O-P or P-C-P. We have labeled IDP with /sup 99m/ Tc quantitatively (98 per cent) using stannous ions as the reducing/complexing agent in a freeze-dried kit form. Radiobioassay of this compound was carried out in rabbits and the results were compared with those of eight other Tc-labeled bone-imaging agents, using the performance of simultaneously administered $sup 85$Sr as a reference standard. The /sup 99m/Tc-IDP concentrated 20 percent higher in the bone, and its soft-tissue and blood levels were lower than with $sup 85$Sr. By comparison,more » the concentrations in the bone of the other /sup 99m/ Tc agents were 20 percent less than that of $sup 85$Sr. Regarding blood levels, Tc-IDP performed worse than the Tc-diphosphonate but better than the pyrophosphate and the other technetium complexes. Scintillation camera images of /sup 99m/ Tc-IDP in both rabbits and dogs showed excellent details of the skeleton. In a preliminary human study, images with /sup 99m/ Tc-IDP were somewhat inferior to those comparably procured with /sup 99m/Tc-methylene diphosphonate, but count rates with the IDP complex were about twice those with the MDP compound. Because of its better bone uptake, however, it is suggested that /sup 99m/Tc-IDP may be clinically useful in spite of its relatively slow blood clearance. (auth)« less
  • An easily formulated, stable kit preparation of technetium-99m HIDA, suitable for use in humans, was developed and tested in mice and dogs. The tracer was cleared rapidly from the blood and excreted predominantly by the liver in both species. In dogs, the hepatobiliary clearance of Tc-99m HIDA was significantly greater than that of C-14 HIDA and Sn-113 HIDA. The LD/sub 50/ for HIDA in mice, 168 mg/kg, exceeded the average human dose by a factor of 1000 on a per-weight basis. Blood clearance curves for Tc-99m HIDA in 12 normal subjects were biexponential with half-times of 4.6 +- 1.0 minmore » and 31.5 +- 7.0 min, and cumulative 90-min urine samples contained 14.2 +- 1.8% of the injected dose. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and activity was present within the biliary system in 10 to 20 min. In jaundiced patients, the tracer blood clearance was delayed and urinary excretion increased, but intestinal activity, indicating biliary patency, was imaged in those patients without complete focal obstruction of the common duct. Technetium-99m HIDA is a nontoxic radiopharmaceutical useful for clinical evaluation of hepatobiliary disorders in humans.« less