Novel radiopharmaceutical, Sm-153-labelled thermoresponsive polymer, for local radiotherapy of solid tumors

«Radiation and Risk», 2018, vol. 27, No. 1, pp.66-76

DOI: 10.21870/0131-3878-2018-27-1-66-76

Authors

Petriev V.M.^1,2 – Lead. Researcher, D. Sc., Biol., Prof. of MEPhI. A. Tsyb MRRC, Obninsk. National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Moscow. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: (484) 399-71-00; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Tishchenko V.K.¹ – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk.
Smorizanova O.A.¹ – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk.
Mikaylovskaya A.A.¹ – Senior Researcher, C. Sc., Biol. A. Tsyb MRRC, Obninsk.
Bol’bit N.M.³ – Lead. Technologist, C. Sc., Chem. Branch of L. Karpov Research Institute of Physical Chemistry, Obninsk.
Duflot V.R.³ – Director, D. Sc., Chem. Branch of L. Karpov Research Institute of Physical Chemistry, Obninsk.
Gayvoronsky A.V.³ – Engineer. Branch of L. Karpov Research Institute of Physical Chemistry, Obninsk.
Morozova N.B.⁴ – Research Assistant, C. Sc., Biol. P. Hertsen Moscow Oncology Research Center, Moscow
Yakubovskaya R.I.⁴ – Head of Dep., D. Sc., Biol. P. Hertsen Moscow Oncology Research Center, Moscow

Abstract

Results of the study of pharmacokinetic properties of the novel radiopharmaceutical, ¹⁵³Sm-labelled thermoresponsive polymer, designed for local radiotherapy of solid tumors are presented. The pharmacokinetics of the drug in F1 mice bearing subcutaneous sarcoma S37 and in С57Bl/6 mice with subcutaneous melanoma B16. The radiopharmaceutical was injected into tumor xenografts (0.18-0.37 MBq, 0.1 ml). The mice were sacrificed under anesthesia in 5 min, 1, 3, 24, 72 and 168 h after the drug administration. The organs of interest were excised, weighed and radioactivity was measured in an automated gamma-counter. The highest radioactivity was in the tumor tissue (i.e. at the site of injection). In 7 days after injection the radioactivity level in sarcoma S37 was 57.2% of injected dose (ID) and 42.2% ID was in melanoma B16. The radiolabeled compound exhibited a higher tumor retention in sarcoma S37 bearing mice compared to the retention in melanoma B16 tumor xenografts, especially at later time following the radiopharmaceutical administration. The peak radioactivity in the liver was 1.14% ID/g. The transient uptake of radiolabeled compound was registered in the stomach (up to 4.22% ID/g in 5 min), the lungs (up to 1.15% ID/g in 1 h) and the skin (up to 1.34% ID/g in 1 h), later it declined rapidly. High level of radioactivity was registered in kidneys as the most of the radiopharmaceutical excreted in the urine. The activity level in the thyroid gland, spleen, heart, brain, intestine, muscle and femur was lower than 1% ID/g throughout the study. The activity in the soft organs and tissues in sarcoma S37 bearing mice and in melanoma B16 beating mice was roughly of similar level. In conclusion, the presented results allow us to suggest that theradiopharmaceutical has exciting potential for local tumor therapy.

Key words
radiopharmaceutical, thermoresponsive polymer, ¹⁵³Sm, pharmacokinetic properties, radionuclide therapy, radiobiological effects, sarcoma S37, melanoma B16, coefficient of differential accumulation, N-izopropilakrilamid, N-Methacrylonitrile, diethylentriaminepentaacetic acid.

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