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

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