Zirconium tetraazamacrocycle complexes display extraordinary stability and provide a new strategy for zirconium-89-based radiopharmaceutical development.
Zirconium tetraazamacrocycle complexes display extraordinary stability and provide a new strategy for zirconium-89-based radiopharmaceutical development.
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DOI：
10.1039/c6sc04128k
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发表时间：
2017-03-01
期刊：
影响因子：
8.4
通讯作者：
Wadas TJ
中科院分区：
文献类型：
--
作者：
Pandya DN;Bhatt N;Yuan H;Day CS;Ehrmann BM;Wright M;Bierbach U;Wadas TJ
89 Zr-四氮杂大环配合物显示出非凡的稳定性。我们报告我们的初步调查使用四氮杂大环作为锆-89螯合剂。本文报道了几种锆四氮杂大环配合物的合成和表征，并利用单晶X射线衍射分析确定了锆1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸（Zr-DOTA）的第一晶体结构。在评估了几种放射性类似物后，我们发现89 Zr-DOTA上级89 Zr-DFO，89 Zr-DFO是临床上唯一用于89 Zr-放射性药物应用的89 Zr-络合物。最后，我们提供了这些复合物在体外和体内的意外和非凡的稳定性的理由。这些结果可以为开发更安全，更强大的免疫PET试剂提供信息，用于精确医学应用。
89Zr–Tetraazamacrocycle complexes display extraordinary stability. We report our initial investigations into the use of tetraazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of several Zr tetraazamacrocycle complexes, and definitively describe the first crystal structure of zirconium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Zr–DOTA) using single crystal X-ray diffraction analysis. After evaluating several radioactive analogs, we found that 89Zr–DOTA is superior to 89Zr–DFO, the only 89Zr-complex to be used clinically in 89Zr-radiopharmaceutical applications. Finally, we provide a rationale for the unanticipated and extraordinary stability of these complexes in vitro and in vivo. These results may inform the development of safer and more robust immuno-PET agents for precision medicine applications.