Preclinical Studies of Radiopharmaceutical Based on Thermo-Sensitive Copolymer and Samarium-153 for Local Radionuclide Therapy of Solid Tumors

Results of the study of pharmacokinetic properties of the novel radiopharmaceutical, ¹⁵³Sm-labelled thermosensitive copolymer, designed for local radiotherapy of solid tumors are presented. We studied the pharmacokinetic properties of a new radiopharmaceutical based on a temperature-sensitive copolymer and samarium-153 (CASP‑CM, ¹⁵³Sm – Collapsing Aqueous Solution of Polymer, Chelated by Samarium-153) for local radiotherapy of solid tumors. The biodistribution study was conducted on F1 and C57Bl/6 mices with S37 implanted subcutaneously with sarcoma and B16 melanoma, respectively, with intratumoral administration of the drug. In addition, biological studies of the local irritating action, acute and subchronic toxicity of the non-radioactive analogue CASP-CM, ¹⁵²Sm are presented. The results showed that the greatest amount of activity was observed in the tumor tissue (i.e. at the injection site). 7 days after the injection, the activity level in the sarcoma S37 tissue was 57.2 % of the administered dose, and in the B16 melanoma tissue – 42.2 % of the administered dose. At the same time, the retention of the labeled drug with tumor tissue of S37 sarcoma is higher than with B16 melanoma tissue, especially in the later stages of the study. The peak activity in the liver was 1.14 %/g. A transient increase in the concentration of the labeled drug was observed in the stomach (up to 4.22 %/ g after 5 min), lungs (up to 1.15 %/ g after 1 h) and skin (up to 1.34 %/g after 1 h), however then the concentration rapidly decreased. An increased level of activity was observed in the kidneys, since most of it was excreted through the urinary system. The concentration of activity in the thyroid gland, spleen, heart, brain, small intestine, muscle tissue and femur was below 1 %/g throughout the study period. Statistically significant differences between the levels of activity in the internal organs and tissues in mice with S37 sarcoma and B16 melanoma were practically not detected. The study of local tolerance, acute toxicity and subchronic toxicity of a model non-radioactive preparation using different routes of administration (subcutaneous and intramuscular) in mice, rats and rabbits showed that the model preparation CASP-CM,¹⁵²Sm, when administered subcutaneously, does not lead to the development of pronounced local pathological reactions; according to the degree of danger of acute and chronic toxic action, it is of low toxicity. On the basis of the data obtained, it is also possible to make a conclusion about the safety of the polymer carrier of samarium isotope based on poly-N-isopropylacrylamide. In conclusion, the presented results allow us to suggest that the radiopharmaceutical has exciting potential for local tumor therapy.

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