STUDY OF FUNCTIONAL SUITABILITY TUMOR TROPISM RADIOPHARMACEUTICALS 99MTС-1-THIO-D-GLUCOSE IN THE EXPERIMENT

DOI: https://doi.org/10.29296/24999490-2018-03-11

R.V. Zelchan(1), A.A. Medvedeva(1), I.G. Sinilkin(1), O.D. Bragina(1), V.I. Chernov(1, 2), E.S. Stasyuk(2), E.A. Ilina(2), V.S. Skuridin(2) 1-Tomsk National Research Medical Center, Kooperativny by-street, 5, Tomsk, 634009, Russian Federation; 2-National Research Tomsk Polytechnic University, Tomsk Polytechnic University, Lenina Avenue, 30, Tomsk, 634050, Russian Federation E-mail: [email protected]

Aim of the study: to study the possibility of the use of glucose derivative labeled with 99mTc for cancer imaging in the experiment. Materials and method: the study was performed in cell culture of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). In tubes with cells in an amount of 3 million, there was introduced 25 MBq glucose derivative labeled with 99mTc and incubated for 30 minutes at room temperature. After a centrifugation of the tube with cells the supernatant was removed. Then the measurement of radioactivity in tubes with normal and tumor cells was made. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions model in mice, the rewas used carcinoma Lewis. Following anesthesia, mice were injected intravenously with the 25 MBq glucose derivative labeled with 99mTc. After 15 minutes planar scintigraphy was performedin a matrix of 512×512 pixels for 5 minutes. Results. By means of the measurement of the radioactivity of normal and malignant cells after incubation with the glucose derivative labeled with 99mTc radioactivity of malignant cells was found to be higher. Mean values of radioactivity levels in normal cells were of 0,3±0,15 MBq Mean values of the level of radioactivity in the malignant cells were of 1,07±0,6 MBq. All examined animals were revealed to have increased accumulation of the glucose derivative labeled with 99mTc at the tumor site. The accumulation of the glucose derivative labeled with 99mTc in the tumor was on average twice as high as compared to the symmetric region. The mean value of the index tumor/background ratio was 2,15±0,35. Conclusion. The present study demonstrated glucose derivative labeled with 99mTc to be a prospective radiopharmaceutical for the cancer visualization. In addition, high accumulation of the glucose derivative labeled with 99mTcin the culture of cancer cells and in animals tumor tissue demonstrates tumor tropism of the radiopharmaceutical
Keywords: 
radiopharmaceuticals, glucose derivatives, oncology
Список литературы: 
  1. Nacional`noe rukovodstvo po radionuklidnoy diagnostike. Pod red. Lishmanov Yu.B., Chernov V.I., Tomsk: STT. 2010; Tom 1. [Nacional’noe rukovodstvo po radionuklidnoj diagnostike. Pod red. Lishmanov Ju.B., Chernov V.I., Tomsk: STT. 2010; Tom 1 (in Russian)]
  2. Van Noorden R. Radioisotopes: The medical testing crisis. Nature. 2013; 504 (7479): 202–4.
  3. Chernov V.I., Bragina O.D., Sinilkin I.G., Tickaya A.A., Zel`chan R.V. Radioimmunoterapiya v lechenii zlokachestvennyh obrazovaniy. Sibirskiy onkologicheskiy zhurnal. 2016; 15 (2): 101–6. [Chernov V.I., Bragina O.D., Sinilkin I.G., Tickaya A.A., Zel’chan R.V. Radioimmunotherapy in the treatment of malignant tumors. Sibirskij onkologicheskij zhurnal. 2016; 15 (2): 101–6 (in Russian)]
  4. Chernov V.I., Bragina O.D., Sinilkin I.G., Medvedeva A.A., Zel`chan R.V. Radionuklidnaya teranostika zlokachestvennyh obrazovaniy. Vestnik rentgenologii i radiologii. 2016; 97 (5): 306–13. [Chernov V.I., Bragina O.D., Sinilkin I.G., Medvedeva A.A., Zel’chan R.V. Radionuclide terorectics of malignant tumors. Vestnik rentgenologii i radiologii. 2016; 97 (5): 306–13 (in Russian)]
  5. Chernov V.I., Bragina O.D., Sinilkin I.G., Medvedeva A.A., Zel`chan R.V. Radioimmunoterapiya: sovremennoe sostoyanie problemy. Voprosy onkologii. 2016; 62 (1): 24–30. [Chernov V.I., Bragina O.D., Sinilkin I.G., Medvedeva A.A., Zel’chan R.V. Radioimmunotherapy: the current state of the problem. Voprosy onkologii. 2016; 62 (1): 24–30 (in Russian)]
  6. Baum R.P., Schmuecking M., Bonnet R. F-18 FDG PET for metabolic 3D-radiation treatment planning of non-small cell lung cancer. Eur. J. Nucl. Med. and Mol. Imag. 2002; 43: 96–9.
  7. Jacobson MS, Hung JC, Mays TL, Mullan BP. The planning and design of a new PET radiochemistry facility. Mol. Imaging Biol. 2002; 4 (2): 119–27.
  8. Takekawa H., Takaoka K., Tsukamoto E. et al. Visualization of lung cancer with 99mTc-tetrofosmin imaging: a comparison with 201T1. Nucl. Med. Commun. 1997; 18: 341–5.
  9. Usov V.Yu., Ryanel` Yu.E`., Medvedeva A.A., Popadich S., Slonimskaya E.M., Velichko S.A., Barysheva E.V., Kolesnikov S.A. Mammoscintigrafiya s 99mTc-tehnetrilom, v ocenke sostoyaniya pervichnoy opuholi pri himioterapii raka molochnoy zhelezy. Medicinskaya vizualizaciya. 2002; 2: 86. [Usov V.Yu., Ryanel’ Yu.E., Medvedeva A.A., Popadich S., Slonimskaya E.M., Velichko S.A., Barysheva E.V., Kolesnikov S.A. Mammotsvintigrafiya with 99mTc-technetril, in assessing the condition of the primary tumor in chemotherapy for breast cancer. Medicinskaya vizualizaciya. 2002; 2: 86 (in Russian)]
  10. Chernov V.I., Zel`chan R.V., Tickaya A.A., Sinilkin I.G., Chizhevskaya S.Yu., Surkova P.V., Choynzonov E.L. Primenenie gamma-scintigrafii s 99mTc-tehnetrilom v kompleksnoy diagnostike i ocenke e`ffektivnosti neoad``yuvantnoy himioterapii zlokachestvennyh opuholey gortani i gortanoglotki. Medicinskaya radiologiya i radiacionnaya bezopasnost`. 2011; 56 (2): 38–43. [Chernov V.I., Zel’chan R.V., Tickaja A.A., Sinilkin I.G., Chizhevskaja S.Ju., Surkova P.V., Chojnzonov E.L. The use of gamma scintigraphy with 99mTc-technetril in complex diagnostics and evaluation of neoadjuvant chemotherapy of malignant tumors of the larynx and hypopharynx. Medicinskaja radiologija i radiacionnaja bezopasnost’. 2011; 56 (2): 38–43 (in Russian)]
  11. Chernov V.I., Kravchuk T.L., Zel`chan R.V., Gol`dberg V.E. E`kg-sinhronizirovannaya perfuzionnaya tomoscintigrafiya miokarda s 99mTc-tehnetrilom v ocenke ostroy i hronicheskoy kardiotoksichnosti himioterapevticheskih preparatov. Medicinskaya radiologiya i radiacionnaya bezopasnost`. 2012; 57 (4): 32–9. [Chernov V.I., Kravchuk T.L., Zel’chan R.V., Gol’dberg V.E. ECG-synchronized perfusion tomoscintigraphy of myocardium with 99mTc-technetril in the assessment of acute and chronic cardiotoxicity of chemotherapeutic drugs. Medicinskaya radiologiya i radiacionnaya bezopasnost’. 2012; 57 (4): 32–9 (in Russian)]
  12. Cheng D., Rusckowski M., Wang Y., Liu Y., Liu G., Liu X., Hnatowich D. A Brief Evaluation of Tumor Imaging in Mice with 99mTc-glucarate Including a Comparison with 18F-FDG. Curr. Radiopharm. 2011; 4 (1): 5–9.
  13. Chernov V.I., Medvedeva A.A., Sinilkin I.G., Zel`chan R.V., Bragina O.D., Skuridin V.S. Opyt razrabotki innovacionnyh radiofarmpreparatov v Tomskom NII onkologii. Sibirskiy onkologicheskiy zhurnal. 2015; 2: 45–7. [Chernov V.I., Medvedeva A.A., Sinilkin I.G., Zel’chan R.V., Bragina O.D., Skuridin V.S. Experience in the development of innovative radiopharmaceuticals in the Tomsk Institute of Oncology. Sibirskij onkologicheskij zhurnal. 2015; 2: 45–7 (in Russian)]
  14. Welling M.M., Alberto R. Performance of a 99mTc-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue in the detection of infections and tumours in mice: a comparison with [18F]FDG. Nucl. Med. Commun. 2010; 31 (3): 239–48.
  15. Federal`naya celevaya programma «Razvitie farmacevticheskoy i medicinskoy promyshlennosti Rossiyskoy Federacii na period do 2020 goda i dal`neyshuyu perspektivu». Doklinicheskie issledovaniya radiofarmacevticheskogo preparata na osnove mechennoy 99mTs proizvodnoy glyukozy dlya radionuklidnoy diagnostiki onkologicheskih zabolevaniy. Gosudarstvennyy kontrakt №14.N08.11.0033 ot 19.05.2015. [The federal target program «Development of the Pharmaceutical and Medical Industry of the Russian Federation for the period up to 2020 and beyond». Preclinical studies radiopharmaceutical based on 99mTc-labeled derivative of glucose for radionuclide diagnosis of cancer. State contract №14.N08.11.0033 on 19/05/2015 (in Russian)]