一种¹⁸⁶Re络合物共轭双膦酸盐对动物模型中转移性骨痛缓解的治疗效果。

Therapeutic effects of a 186Re-complex-conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model.

作者信息

Ogawa Kazuma, Mukai Takahiro, Asano Daigo, Kawashima Hidekazu, Kinuya Seigo, Shiba Kazuhiro, Hashimoto Kazuyuki, Mori Hirofumi, Saji Hideo

机构信息

Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

出版信息

J Nucl Med. 2007 Jan;48(1):122-7.

PMID:17204708

Abstract

UNLABELLED

Previously, based on the concept of bifunctional radiopharmaceuticals, we developed a highly stable (186)Re-mercaptoacetylglycylglycylglycine (MAG3) complex-conjugated bisphosphonate, [[[[(4-hydroxy-4,4-diphosphonobutyl)carbamoylmethyl]carbamoylmethyl]carbamoylmethyl]carbamoylmethanethiolate] oxorhenium(V) ((186)Re-MAG3-HBP), for the treatment of painful bone metastases. This agent showed a superior biodistribution as a bone-seeking agent in normal mice when compared with (186)Re-1-hydroxyethylidene-1,1-diphosphonate ((186)Re-HEDP). In this study, we evaluated the therapeutic effects of (186)Re-MAG3-HBP using an animal model of bone metastasis.

METHODS

The model was prepared by injecting syngeneic MRMT-1 mammary tumor cells into the left tibia of female Sprague-Dawley rats. (186)Re-MAG3-HBP (55.5, 111, or 222 MBq/kg) or (186)Re-HEDP (55.5 MBq/kg) was then administered intravenously 21 d later. To evaluate the therapeutic effects and side effects, tumor size and peripheral blood cell counts were determined. Palliation of bone pain was evaluated by a von Frey filament test.

RESULTS

In the rats treated with (186)Re-HEDP, tumor growth was comparable with that in untreated rats. In contrast, when (186)Re-MAG3-HBP was administered, tumor growth was significantly inhibited. Allodynia induced by bone metastasis was attenuated by treatment with (186)Re-MAG3-HBP or (186)Re-HEDP, but (186)Re-MAG3-HBP tended to be more effective.

CONCLUSION

These results indicate that (186)Re-MAG3-HBP could be useful as a therapeutic agent for the palliation of metastatic bone pain.

摘要

未标记

此前，基于双功能放射性药物的概念，我们开发了一种高度稳定的（186）铼-巯基乙酰甘氨酰甘氨酰甘氨酸（MAG3）复合物偶联双膦酸盐，[[[[(4-羟基-4,4-二膦酸丁基)氨基甲酰甲基]氨基甲酰甲基]氨基甲酰甲基]氨基甲酰甲硫醇盐]氧铼（V）（（186）铼-MAG3-HBP），用于治疗疼痛性骨转移。与（186）铼-1-羟基亚乙基-1,1-二膦酸盐（（186）铼-HEDP）相比，该药物在正常小鼠中作为亲骨剂显示出更好的生物分布。在本研究中，我们使用骨转移动物模型评估了（186）铼-MAG3-HBP的治疗效果。

方法

通过将同基因MRMT-1乳腺肿瘤细胞注射到雌性Sprague-Dawley大鼠的左胫骨制备模型。然后在21天后静脉注射（186）铼-MAG3-HBP（55.5、111或222 MBq/kg）或（186）铼-HEDP（55.5 MBq/kg）。为了评估治疗效果和副作用，测定肿瘤大小和外周血细胞计数。通过von Frey细丝试验评估骨痛的缓解情况。