Srivastava P C, Buchsbaum D J, Allred J F, Brubaker P G, Hanna D E, Spicker J K
Oak Ridge National Laboratory, TN 37831-6022.
Biotechniques. 1990 May;8(5):536-45.
A new radioiodinating agent, N-(p-[125I]iodophenyl)maleimide, has been synthesized for its potential utility in the radioiodination of monoclonal antibodies and other proteins. The efficiency of incorporation of 125I in the B72.3 antibody by iodine monochloride iodination or by maleimide conjugation was 19% and 43%, respectively. The thyroid uptake following intraperitoneal administration of the two 125I-labeled antibody preparations was evaluated in nude mice implanted with LS174T colon carcinoma xenografts. The iodine monochloride preparation showed substantially greater uptake in the thyroid with values of 2.1% ID at 6 h after injection and reaching a maximum of 4.3% ID after 6 days. In contrast, the maleimide preparation showed a uniformly low uptake in thyroid of 0.1%-0.2% ID. The results of these preliminary studies demonstrate that the N-(p-[125I]iodophenyl)maleimide-labeled monoclonal antibodies showed markedly less (less than 10-fold) uptake of radioiodine in the thyroid, indicating significantly less in vivo deiodination than iodine monochloride-labeled monoclonal antibodies, while retaining some tumor localization in vivo. Studies are in progress to optimize N-(p-[125I]iodophenyl)maleimide radioiodination conditions and to improve the tumor localization.
一种新型放射性碘化剂N-(对-[125I]碘苯基)马来酰亚胺已被合成，因其在单克隆抗体和其他蛋白质的放射性碘化方面具有潜在用途。通过一氯化碘碘化或马来酰亚胺偶联将125I掺入B72.3抗体的效率分别为19%和43%。在植入LS174T结肠癌异种移植物的裸鼠中评估了腹腔注射两种125I标记抗体制剂后的甲状腺摄取情况。一氯化碘制剂在甲状腺中的摄取明显更高，注射后6小时的值为2.1%ID，6天后最高达到4.3%ID。相比之下，马来酰亚胺制剂在甲状腺中的摄取始终较低，为0.1%-0.2%ID。这些初步研究结果表明，N-(对-[125I]碘苯基)马来酰亚胺标记的单克隆抗体在甲状腺中摄取的放射性碘明显较少（小于10倍），表明其体内脱碘明显少于一氯化碘标记的单克隆抗体，同时在体内仍保留一定的肿瘤定位。目前正在进行研究以优化N-(对-[125I]碘苯基)马来酰亚胺的放射性碘化条件并改善肿瘤定位。
