Radioiodination of antibodies via N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates.
Radioiodination of antibodies via N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates.
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通过 N-琥珀酰亚胺基 2,4-二甲氧基-3-(三烷基甲锡烷基)苯甲酸酯对抗体进行放射性碘化。
DOI：
10.1021/bc00006a004
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发表时间：
1990
影响因子：
4.7
通讯作者：
Zalutsky,MR
中科院分区：
文献类型：
--
作者：
Vaidyanathan,G;Zalutsky,MR
我们以前已经表明，使用IV-琥珀酰亚胺基3-碘苯甲酸酯（SIB）的单克隆抗体（MAbs）的放射性碘标记减少放射性碘在体内的损失相比，通过使用常规方法标记的MAbs。本文描述了2，4-二甲氧基-3-（三烷基甲锡烷基）-苯甲酸IV-琥珀酰亚胺酯（烷基=Me，Bu）的合成，以及它们作为放射合成2，4-二甲氧基-3-碘苯甲酸IV-琥珀酰亚胺酯（SDMIB）的前体的用途。用SDMIB标记的MAb F（ab '）2片段保留其特异性结合肿瘤匀浆的能力。配对标记组织分布研究表明，水解SDMIB的甲状腺摄取（脱碘的指标）约为水解SIB的20倍。相比之下，当与MAb缀合时，SDMIB的甲状腺摄取仅为SIB的1.4-2.8倍，并且显著低于文献中报道的通过使用直接亲电碘化方法标记的MAb的水平。虽然用SDMIB标记的单克隆抗体比用常规方法标记的单克隆抗体对脱卤更惰性，但与原始SIB试剂相比，添加两个甲氧基降低了标记物在体内的保留。
We have previously shown that use of IV-succinimidyl 3-iodobenzoate (SIB) for radioiodination of mon-oclonal antibodies (MAbs) decreases the loss of radioiodine in vivo compared to MAbs labeled by using conventional methods. Herein, the synthesis of IV-succinimidyl 2, 4-dimethoxy-3-(trialkylstannyl)-benzoates (alkyl=Me, Bu) are described as is their use as precursors for the radiosynthesis of IV-suc-cinimidyl 2, 4-dimethoxy-3-iodobenzoate (SDMIB). A MAb F (ab') 2 fragment labeled with SDMIB retained its ability to bind specifically to tumor homogenates. Paired-label tissue distribution studies indicate that the thyroid uptake (an indicator of deiodination) of hydrolyzed SDMIB was about 20 times that of hydrolyzed SIB. In contrast, thyroid uptake for SDMIB, when conjugated to a MAb, was only 1.4-2.8 times that for SIB and was considerably lower than levels reported in the literature for MAbs labeled by using direct, electrophilic iodination methods. Although MAbs labeled with SDMIB are significantly more inert to dehalogenationthan those labeled by conventional methods, compared to theoriginal SIB reagent, addition of two methoxy groups decreased retention of label in vivo.