BACKBONE-SUBSTITUTED DTPA LIGANDS FOR Y-90 RADIOIMMUNOTHERAPY
BACKBONE-SUBSTITUTED DTPA LIGANDS FOR Y-90 RADIOIMMUNOTHERAPY
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DOI：
10.1021/bc00009a008
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发表时间：
1991-05-01
影响因子：
4.7
通讯作者：
GANSOW, OA
中科院分区：
文献类型：
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作者：
BRECHBIEL, MW;GANSOW, OA
合成了四个新的双功能二亚乙基三胺五乙酸（DTPA）配体，为Y-90的放射免疫治疗提供了一种改进的螯合剂。新的DTPA配体含有取代到DTPA的碳骨架上的4-异硫氰酸根合苄基（pSCNBz），用于连接免疫蛋白。通过肽途径将甲基策略性地结合到配体的主链上，以提供2-pSCNBz-5-Me-DTPA（2）和3-Me-6-pSCNBz-DTPA（3）。预期添加这些官能团会在空间上阻碍放射性金属从螯合物中释放。还制备了一种新的单取代配体3-pSCNBz-DTPA（4），以确定连接基团的位置变化是否对钇络合物的体内稳定性产生影响。此外，通过改进已知方法，制备了二取代DTPA配体2-pSCNBz-6-Me-DTPA（1）。
Four new bifunctional diethylenetriaminepentaacetic acid (DTPA) ligands were synthesized to provide an improved chelating agent for radioimmunotherapy with Y-90. The new DTPA ligands contained a 4-isothiocyanatobenzyl group (pSCNBz) substituted onto the carbon backbone of DTPA for use in linkage to immunoprotein. Methyl groups were strategically incorporated onto the backbone of the ligands via a peptide route to provide 2-pSCNBz-5-Me-DTPA (2) and 3-Me-6-pSCNBz-DTPA (3). Addition of these functionalities was expected to sterically hinder the release of radiometal from the chelate. A new monosubstituted ligand, 3-pSCNBz-DTPA (4), was also prepared in order to determine whether a shift in position of the linking group had an effect on the in vivo stability of the yttrium complex. Additionally, by modification of known methods, a disubstituted DTPA ligand, 2-pSCNBz-6-Me-DTPA (1), was prepared.