Pharmacokinetic properties and antitumor efficacy of a new radiopharmaceutical based on Sm-153 and thermoresponsive carrier in a tumor model of hepatocholangioma RS-1

«Radiation and Risk», 2019, vol. 28, No. 2, pp.124-133

DOI: 10.21870/0131-3878-2019-28-2-124-133

Authors

Petriev V.M.^1,2 – Lead. Researcher, D. Sc., Biol., Prof. of MEPhI. 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.
Smoryzanova O.A.¹ – Senior Researcher, C. Sc., Biol.
Mikailovskaya A.A.¹ – Senior Researcher, C. Sc., Biol.
Bolbit N.M.³ – Lead. Technologist, C. Sc., Chem.
Duflot V.R.³ – Director, D. Sc., Chem.
Morozova N.B.⁴ – Research Assistant, C. Sc., Biol.
Yakubovskaya R.I.⁴ – Head of Dep., D. Sc., Biol. P. Hertsen MORC.

¹A. Tsyb MRRC, Obninsk, Russia
²National Research Nuclear University MEPhI, Moscow, Russia
³L. Karpov Research Institute of Physical Chemistry, Obninsk, Russia
⁴P. Hertsen Moscow Oncology Research Center, Moscow

Abstract

Thermoresponsive polymers have attracted great interest due to their unique properties. A new radiopharmaceutical (RPC) based on thermoresponsive polymer as a carrier and ^153Sm was developed for application in local radiotherapy of solid cancer. When heated above 37 °C, it collapses and forms unsoluble gel that restricts its motility at the site of injection and distribution the radioactivity throughout the body. All studies were performed in Wistar rats with subcutaneous tumor xenografts of hepatocholagioma RS-1 after single intratumoral administration of RPC. The pharmacokinetic properties were studied by radioactivity measurements the samples of organs and tissues after injection of 0.18-0.37 MBq (5-10 mCi) in a volume of 0.1 ml. To evaluate the antitumor efficacy, animals were treated with 37 MBq (1 mCi) or 18.5 MBq (0.5 mCi) of RPC. The results revealed that the greatest amount of injected radioactivity remained in tumor. The tumor concentrations of radiopharmaceutical were 92.50%, 85.91%, 85.85%, 74.72%, 71.51% and 68.74% of injected dose (ID) at 5 min, 1, 3, 24, 72 and 168 h post-injection, respectively. The amounts of radioactivity in other organs and tissues did not exceed 1% of ID/g. RPC didn’t exert significant antitumor efficacy. Tumor growth inhibition index reached 37.3% and 30.6%, and increase of average life span was 25.5% and 20.9% in groups of animals after treatment with 37 MBq and 18.5 MBq of RPC, respectively. In conclusion, a new radiopharmaceutical based on thermoresponsive polymer and ¹⁵³Sm is a promising agent for local radiotherapy of cancer.

Key words
Thermoresponsive polymer, poly(N-isopropylacrylamide), ¹⁵³Sm, radiopharmaceutical, local radiotherapy, radiotherapy of cancer, intratumoral injection, Wistar rats, hepatocholangioma PC-1, antitumor efficacy.

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