Оценка влияния условий приготовления остеотропного препарата «188Re гидроксиэтилидендифосфоновая кислота» на его фармакокинетику в организме крыс

Abstract

In this experimental work, in vivo biodistributions of a bone-seeking radiopharmaceutical, monopotassium salt of hydroxyethylidenediphosphonate labeled by 188Re (188Re-KHEDP), have been studied in rats for drug batches obtained under different conditions. First, we have evaluated 188Re-KHEDP samples prepared with and without 188Re carrier. Then we have studied the pharmacokinetics of two batches of 188Re-KHEDP, which were synthesized at different temperatures (20 and 100°С). Results showed that all preparations of 188Re-KHEDP accumulated in the skeletal system. The excretory pathway of 188Re-KHEDP was through the kidney. Only kidney and thyroid gland exhibited a relatively high drug uptake among the soft tissue organs. The results showed that carrier-added 188Re-KHEDP had better pharmacokinetic parameters than the carrier-free radiopharmaceutical, as manifested by higher skeletal uptake, faster blood clearance, and relatively lower absorption in soft tissues. It was also found that the presence of an 188Re carrier significantly increases the stability of 188Re-KHEDP. The bone-to-muscle ratio was 249.1 ± 42.1 in the 188Re-KHEDP prepared with carrier and below 21 in the carrier-free batch. The biodistribution patterns of 188Re-KHEDP were found to differ for the drugs prepared at 20 and 100°C. The maximum bone-to-muscle and bone-to-blood ratios were 157.3 ± 24.4 and 21/4 ± 4.85 in for 188Re-KHEDP heated to 20°C against 467.2 ± 123.2 and 77.9 ± 11.9 for 188Re-KHEDP heated to 100°C. These results showed a significant (p < 0.05) difference in favor of 188Re-KHEDP heated to 100°C. The results indicated that all variants of 188Re-KHEDP had promising properties as potential therapeutic bone-seeking agents, but carrier-added 188Re-KHEDP and 188Re-KHEDP heated to 100°C exhibited better properties than other types of examined radiopharmaceuticals.