Mixed bis(thiosemicarbazone) ligands for the preparation of copper radiopharmaceuticals: synthesis and evaluation of tetradentate ligands containing two dissimilar thiosemicarbazone functions.
Mixed bis(thiosemicarbazone) ligands for the preparation of copper radiopharmaceuticals: synthesis and evaluation of tetradentate ligands containing two dissimilar thiosemicarbazone functions.
复制标题
用于制备铜放射性药物的混合双（缩氨基硫脲）配体：含有两个不同的缩氨基硫脲官能团的四齿配体的合成和评估。
DOI：
10.1021/jm9605703
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Green,MA
中科院分区：
文献类型：
--
作者：
Lim,JK;Mathias,CJ;Green,MA
A series of four “mixed” bis(thiosemicarbazone) keto aldehyde derivatives containing dissimilar thiosemicarbazone functions were synthesized and evaluated as ligands for preparation of radiocopper-labeled radiopharmaceuticals. The pyruvaldehyde-based mixed bis(thiosemicarbazone) ligands CH3C[NNHC(S)NH2]CH[NNHC(S)NHMe] (4a), CH3C[NNHC(S)NHMe]CH[NNHC(S)NH2] (4b), CH3C[NNHC(S)NH2]CH[NNHC(S)NMe2] (4c), and CH3C[NNHC(S)NHMe]CH[NNHC(S)NMe2] (4d) were obtained by reaction of thiosemicarbazide,N4-methylthiosemicarbazide, orN4,N4-dimethylthiosemicarbazide with pyruvaldehyde 2-thiosemicarbazones that had been generated by oxidative cleavage of the appropriate pyruvic aldehyde dimethyl acetal 2-thiosemicarbazone. The67Cu-labeled complexes of ligands4a−dwere prepared and screened in a rat model to assess the potential of each chelate as a62Cu radiopharmaceutical for imaging with positron emission tomography. In the rat model the67Cu complexes of ligands4a−dexhibit significant uptake into the brain and heart after intravenous injection, following trends similar to those previously reported for the related bis(thiosemicarbazone) complexes, Cu−PTS, Cu−PTSM, and Cu−PTSM2(derived from pyruvaldehyde bis(thiosemicarbazone), pyruvaldehyde bis(N4-methylthiosemicarbazone), and pyruvaldehyde bis(N4,N4-dimethylthiosemicarbazone), respectively). Ultrafiltration studies using solutions of dog and human serum albumin reveal that the67Cu complexes of ligands4a−d, like the Cu(II) complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), interact more strongly with human albumin than dog albumin.
