188Re(CO)3-Dipicolylamine-Alendronate: A New Bisphosphonate Conjugate for the Radiotherapy of Bone Metastases
188Re(CO)3-Dipicolylamine-Alendronate: A New Bisphosphonate Conjugate for the Radiotherapy of Bone Metastases
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DOI：
10.1021/bc100071k
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发表时间：
2010-05-01
影响因子：
4.7
通讯作者：
Blower, Philip J.
中科院分区：
文献类型：
--
作者：
de Rosales, Rafael Torres Martin;Finucane, Ciara;Blower, Philip J.
使用含有铼-188 (Re-188) 等 β 发射体的靶向化合物来缓解骨转移引起的疼痛是一种公认且有效的治疗形式。在这里，我们描述了 Re-188(CO)(3)-二吡啶胺 (DPA)-阿仑膦酸盐的有效合成和临床前评估，这是一种用于骨转移姑息治疗的新型双功能双膦酸盐。 Re-188(CO)(3)-DPA-阿仑膦酸盐可以使用基于试剂盒的方法分两步轻松合成，具有高比活性和产率（18.8 GBq/mg，放射化学产率> = 96%），与临床批准的双膦酸盐Re-186/188-HEDP相比，它形成惰性的单一物种，并已充分表征。体内成像和生物分布研究表明，Re-188(CO)(3)-DPA-alendronate 在高代谢骨活性区域的靶向和积累方面优于 Re-188-HEDP，同时具有低软组织摄取。除了这些研究之外，还描述了一种简单方便的纯化其前体 fac-[Re-188(CO)(3)(H2O)(3)](+) 的新方法。
The palliation of pain due to bone metastases using targeted compounds containing beta-emitters such as rhenium-188 (Re-188) is an accepted and effective form of treatment. Here, we describe the efficient synthesis and preclinical evaluation of Re-188(CO)(3)-dipicolylamine(DPA)-alendronate, a novel bifunctional bisphosphonate for the palliative treatment of bone metastases. Re-188(CO)(3)-DPA-alenclronate can be easily synthesized with high specific activities and yields (18.8 GBq/mg, radiochemical yield >= 96%) in two steps using kit-based methodology, and in contrast with the clinically approved bisphosphonate Re-186/188-HEDP, it forms inert, single species that have been well-characterized. In vivo imaging and biodistribution studies demonstrate that Re-188(CO)(3)-DPA-alendronate is superior to Re-188-HEDP in targeting and accumulating in areas of high metabolic bone activity while having low soft-tissue uptake. In addition to these studies, a simple and convenient new method for purifying its precursor, fac-[Re-188(CO)(3)(H2O)(3)](+), is described.