РЕЗУЛЬТАТЫ ДОКЛИНИЧЕСКИХ ИССЛЕДОВАНИЙ БЕЗОПАСНОСТИ РАДИОФАРМПРЕПАРАТА С 90Y ДЛЯ ВНУТРИАРТЕРИАЛЬНОЙ РАДИОЭМБОЛИЗАЦИИ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙ ПЕЧЕНИ

Abstract

Purpose: Performing a safety study of a radiopharmaceutical drug with yttrium-90 for intra-arterial radioembolization of inoperable patients with primary and metastatic liver cancer.
 Material and methods: The developed radiopharmaceutical is a microspheres of human blood albumin with a diameter of 25-40 microns, modified with diethylenetriaminpentaacetic acid and labeled with 90Y radionuclide. The safety of the radiopharmaceutical was studied by the following indicators: acute toxicity of lyophilized reagents, subchronic toxicity of the radiopharmaceutical on two types of animals, local irritant effect of the radiopharmaceutical therapeutic activity in equivalent terms on laboratory animals, specific toxicity (allergizing effect) of lyophilized reagents for the preparation of a radiopharmaceutical drug. Female and male BALB/C mice, Wistar rats, chinchilla rabbits, and albino Guinea pigs were taken as experimental animals. All animals were obtained from certified laboratory animal nurseries.
 Results: During acute toxicity studies, the maximum safe dose of an inactive drug was determined. In terms of per person, it exceeds the intended dose for clinical use by almost 20 times. The study of the subchronic toxicity of the radiopharmaceutical did not reveal any symptoms of intoxication. The survival rate of the animals during the entire observation period was absolute. Standard behavior and appearance were observed in animals. The dynamics of body weight was positive, and the body temperature of rats and rabbits did not exceed the limits allowed. Samples of the finished dosage form of the drug did not have a local irritant effect. The solution of inactive components of lyophilized reagents for the preparation of a radiopharmaceutical drug did not have an allergenic effect in quantities ten times higher than the doses administered to a person.
 Conclusion: According to the results of preclinical studies, the radiopharmaceutical should be considered safe for use. The results of preclinical studies allow us to recommend the drug for clinical research.