Chemistry of bifunctional photoprobes. 6. Synthesis and characterization of high specific activity metalated photochemical probes: development of novel rhenium photoconjugates of human serum albumin and fab fragments.
Chemistry of bifunctional photoprobes. 6. Synthesis and characterization of high specific activity metalated photochemical probes: development of novel rhenium photoconjugates of human serum albumin and fab fragments.
复制标题
DOI：
10.1021/jo010782u
复制
发表时间：
2002-08
期刊：
影响因子：
--
通讯作者：
R. Rajagopalan;R. R. Kuntz-R.;U. Sharma;W. Volkert;R. Pandurangi
中科院分区：
文献类型：
--
作者：
R. Rajagopalan;R. R. Kuntz-R.;U. Sharma;W. Volkert;R. Pandurangi
描述了通过双功能螯合剂 (BFCA) 对全氟芳基叠氮化物进行官能化，该双功能螯合剂能够与 (99m)Tc（用于 γ 成像）和 (188)Re（用于放射治疗）形成高比活性复合物。还描述了含有 N(2)S(2)、N(4) 和 N(3)S 供体基团的多供体 BFCA 的合成，其中含咪唑、吡啶和吡嗪官能团，这对于调整药代动力学参数可能很重要。全氟芳基叠氮化物在 BFCA 上不同位点的官能化产生了新型双功能光不稳定螯合剂 (BFPCA)，可用于与生物分子共价连接。典型溶剂二乙胺中的代表性 Re-BFPCA 8a 可以高产率地产生分子间 NH 插入产物，且 8a 中的金属离子不会解络。通过分析技术对源自 8a 在二乙胺中光解产生的所有产物进行了表征，并提出了不同光解产物形成的合理机制。 Re-BFPCA 8a 分子间 NH 插入的高产率扩展到在水性条件下标记人血清白蛋白 (HSA) 和 Fab 片段。这里开发的光标记技术提供了一种将诊断和治疗有用的放射性示踪剂（例如，(99m)Tc、(188)Re）附着到 Fab 片段上的新方法，用于潜在的非侵入性成像和癌症治疗。
Functionalization of perfluoro aryl azides by bifunctional chelating agents (BFCAs) capable of forming high specific activity complexes with (99m)Tc (for gamma-imaging) and (188)Re (for radiotherapy) is described. The synthesis of multidonor BFCAs containing N(2)S(2), N(4), and N(3)S donor groups containing imidazole, pyridine, and pyrazine functionalities that may be important for tuning the pharmacokinetic parameters is also described. Functionalization of perfluoro aryl azides at various sites on BFCAs yields novel bifunctional photolabile chelating agents (BFPCAs) that are useful for covalent attachment to biomolecules. A representative Re-BFPCA 8a in a model solvent, diethylamine, proceeded to give a high yield of intermolecular NH insertion product without the decomplexation of the metal ion from 8a. All products originated from the photolysis of 8a in diethylamine are characterized by analytical techniques, and a plausible mechanism of formation of different photolytic products is suggested. The high yield of intermolecular NH insertion of Re-BFPCA 8a is extended to labeling of human serum albumin (HSA) and Fab fragments under aqueous conditions. The photolabeling technology developed here offers a new way to attach diagnostically and therapeutically useful radiotracers (e.g., (99m)Tc, (188)Re) to Fab fragments for potential noninvasive imaging and therapy of cancer.