THE STUDY OF THE ACUTE TOXICITY OF NEW RADIOPHARMACEUTICALS 99mTc-1-thio-D-glucose IN THE EXPERIMENT

DOI: https://doi.org/10.29296/24999490-2019-01-09

R.V. Zelchan(1), A.A. Medvedeva(1), O.D. Bragina(1), I.G. Sinilkin(1), V.I. Chernov(1, 2), E.S. Stasyuk(2), E.A. Tagirova(2), V.S. Skuridin(2) 1Tomsk National Research Medical Center, Kooperativny Street, 5, Tomsk, 634009, Russian Federation; 2National Research Tomsk Polytechnic University, Tomsk Polytechnic University, Lenina Avenue, 30, Tomsk, 634050, Russian Federation E-mail: r.zelchan@yandex.ru

The aim of the study. To investigate the overall acute toxicity of a new radiopharmaceutical in laboratory animals under the selected experimental conditions. Materials and methods. The study was performed on 80 white outbred rats (weight of males 220–260 g, the weight of females 180–240 g, aged of 10 weeks) and 80 white outbred mice (the weight of males 37–40 g, the weight of females 27–29 g, aged of 10 weeks). The studied drug was administered to the animals intravenously and intraperitoneally at three dose levels. Animal monitoring and the assessment of the toxic effect of the studied drug were carried out in strict accordance with the «Guidelines for preclinical drug research», edited by A.N. Mironov. Results. During the entire follow-up period after the administration of the drug, no animal death was observed. Also, no change was revealed in the behavior and in the reflex activity of animals. During the autopsy, there were no macroscopic changes in the main internal organs of the prepared animals. The results of the study showed the actual values of LD50 to be in the range of high doses and are not achievable under the selected experimental conditions. Сonclusion. The results of the presented study showed the safety of the use of the drug 99mTc-1-thio-D-glucose under the selected experimental conditions. According to the results of the study, the drug was classified as referred to a class of moderately toxic substances
Keywords: 
radiopharmaceutical, technetium-99m, glucose derivatives, oncology, acute toxicity

Список литературы: 
  1. Federal`naya celevaya programma «Razvitie farmacevticheskoy i medicinskoy promyshlennosti Rossiyskoy Federacii na period do 2020 g. 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)]
  2. 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)]
  3. 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 teranostics of malignant tumors. Vestnik rentgenologii i radiologii. 2016; 97 (5): 306–13 (in Russian)]
  4. 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.
  5. 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)]
  6. Seidensticker M, Ulrich G, Muehlberg FL, Pethe A et al. Tumor cell uptake of 99mTc-labeled 1-thio-β-D-glucose and 5-thio-D-glucose in comparison with 2-deoxy-2-[18F]fluoro-D-glucose in vitro: kinetics, dependencies, blockage and cell compartment of accumulation. Mol. Imaging Biol. 2014; 16 (2): 189–98. DOI: 10.1007/s11307-013-0690-3.
  7. Stasyuk E.S., Skuridin V.S., Ilina E.A., Rogov A.S., Nesterov E.A., Sadkin V.L., Larionova L.A., Varlamova N.V., Zelchan R.V. Development new radiopharmaceutical based on 5-thio-d- glucose labeled technetium-99m. IOP Conference Series: Materials Science and Engineering «VIII International Scientific Conference «Issues of Physics and Technology in Science, Industry and Medicine»». 2016; 012044.
  8. Zel`chan R.V., Medvedeva A.A., Sinilkin I.G., Bragina O.D., Chernov V.I., Stasyuk E.S., Il`ina E.A., Skuridin V.S. Izuchenie funkcional`noy prigodnosti tumorotropnogo radiofarmpreparata 99mTc-1-TIO-D-glyukoza v e`ksperimente. Molekulyarnaya medicina. 2018; 16 (2): 54 – 57. DOI: 10.29296/24999490-2018-02-
  9. [Zelchan R.V., Medvedeva A.A., Sinilkin I.G., Bragina O.D., Chernov V.I., Stasyuk E.S., Ilina E.A., Skuridin V.S. Study of functional suitability tumor tropism radiopharmaceuticals 99mTs-1-THIO-D-glucose in the experiment. Molekulyarnaya meditsina. 2018; 16 (2): _–_ (in Russian). DOI: 10.29296/24999490-2018-02- (in Russian)]
  10. Mironov A.N. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv. M., 2012; 944.
  11. [Mironov A.N. Rukovodstvo po provedeniyu doklinicheskih issledovanij lekarstvennyh sredstv. M., 2012; 944 (in Russian)]