Evaluation of the influence of preparation conditions on pharmacokinetics of bone-seeking radiopharmaceutical 188Re-labeled hydroxyethylidenediphosphonic acid monopotassium salt in rats

Abstract

The in vivo biodistributions of the monopotassium salt of hydroxyethylidenediphosphonate labeled with 188Re (188Re-KHEDP) were studied in rats for drug batches prepared with and without Re carrier. Also, the pharmacokinetics of two batches of 188Re-KHEDP that were synthesized at different temperatures (20 and 100°C) were studied. The results showed that all 188Re-KHEDP preparations accumulated in bone. The excretory pathway of 188Re-KHEDP was through the kidneys. Only kidney and thyroid 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 bone uptake and faster blood clearance. It was also found that the presence of Re carrier increased significantly the stability of 188Re-KHEDP. The skeleton-to-muscle ratio was 249.1 ± 42.1 for carrier-added 188Re-KHEDP and <21 for the carrier-free drug. The biodistributions of 188Re-KHEDP differed for drugs prepared at 20 and 100°C. The maximum skeleton-to-muscle and skeleton-to-blood ratios were 157.3 ± 24.4 and 21.4 ± 4.85 for 188Re-KHEDP prepared at 20°C and 467.2 ± 123.2 and 77.9 ± 11.9 for that prepared at 100°C. These results showed a statistically significant difference (p < 0.05) in favor of 188Re-KHEDP prepared at 100°C. The results indicated that all versions of 188Re-KHEDP had promising properties as potential therapeutic bone-metastasis agents. However, carrier-added 188Re-KHEDP and that prepared at 100°C exhibited better properties than the other types of the examined radiopharmaceutical.