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

被引:6
作者
Shiryaeva, V. K. [1 ]
Petriev, V. M. [1 ]
Bryukhanova, A. A. [1 ]
Smoryzanova, O. A. [1 ]
Skvortsov, V. G. [1 ]
Shvert, O. E. [1 ]
机构
[1] Minist Hlth & Social Dev Russian Federat, Med Radiol Res Ctr, Obninsk, Kaluga Region, Russia
关键词
1-hydroxyethylidenediphosphoric acid; rhenium-188; METASTASES; DIPHOSPHONATE; PROSTATE; PAIN;
D O I
10.1007/s11094-012-0818-9
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:443 / 448
页数:6
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