The Pre-clinical Test’s Results of the Efficiency of the Radiopharmaceutical Preperation "DTPA-Microspheres of Albumin, 90Y"

Purpose: Development of technology for producing a radiopharmaceutical based on 90Y labeled modified human blood albumin microspheres, and the study of the functional suitability of this drug in experimental animals. Material and methods: The research team studied the following characteristics of the drug: the distribution and excretion of the drug after its intra-arterial administration; the mechanism of action of the drug in animals with model pathology; therapeutic efficacy of the drug in animals with a liver tumor model. The following physicochemical characteristics of the developed radiopharmaceutical were announced: modified with DTPA and labeled 90Y human blood albumin microspheres, particle size 25-40 microns, radiochemical impurities less than 5.0%, 90Sr radionuclide impurities less than 0.002%, the amount of chemical impurities (Na, Al, Ca, Fe, Cu, Zn, Cd, Pb) not more than 10 μg / GBq, volumetric activity up to 150 mCi / ml at the date of preparation. Sprague Dawley female rats were taken as experimental animals (body weight 220-260 g). Studies were conducted on a model pathology - hepatocellular carcinoma, which occurs in 85% of all malignant tumors of the human liver. Results: in 2018-2019, nine pilot batches of the radiopharmaceutical product satisfying the declared characteristics were developed. Stable inhibition of the growth of tumor lesions by 7.62% was noted. The quality of life in animals with orthotopic tumor foci of hepatocarcinoma treated was better than in animals not treated. Life expectancy in the group of animals treated with the drug was higher than in the group of animals that did not receive treatment by 7.1%. The distribution of the drug was characterized by pulmonary bypass, not exceeding 9% of the injected activity and minimal forwarding into the circulating blood. The radiopharmaceutical was firmly held at the injection site and remained almost unchanged throughout the study. Binding to the tumor site of the drug was characterized by retention of at least 78% of the introduced activity. Conclusion: Conducted preclinical studies of the pharmacokinetics of the drug show its potential suitability for the treatment of liver cancer by radionuclide embolization. According to the results of preclinical studies of the therapeutic effectiveness of the radiopharmaceutical, it should be considered effective for use.