Hylarides M D, Wilbur D S, Reed M W, Hadley S W, Schroeder J R, Grant L M
NeoRx Corporation, Seattle, Washington 98119.
Bioconjug Chem. 1991 Nov-Dec;2(6):435-40. doi: 10.1021/bc00012a010.
Protein sulfhydryl reactive N-(4-[125I]iodophenethyl)maleimide (IPEM, 5) was obtained from N-[4-(tri-n-butylstannyl)phenethyl]maleimide in 59-100% radiochemical yield. Conjugation of 5 to NR-ML-05 Fab, a murine anti-melanoma antibody Fab fragment that had been previously reduced with dithiothreitol (DTT), was effected in an average of 85% yield. Results from in vitro chemical challenges and serum stability studies on the IPEM conjugate of NR-ML-05 Fab (6) indicated a stable covalent attachment of the radioiodine. A biodistribution study of the IPEM conjugate in tumor-bearing athymic nude mice showed lack of significant accumulation of radioiodine in the thyroid and stomach which was an indication of in vivo stability. The observed uptake in tumor was consistent with that obtained for Chloramine-T- or p-iodobenzoate-labeled NR-ML-05 Fab conjugates.
蛋白巯基反应性N-(4-[¹²⁵I]碘苯乙基)马来酰亚胺(IPEM, 5)由N-[4-(三正丁基锡烷基)苯乙基]马来酰亚胺制得，放射化学产率为59 - 100%。5与NR-ML-05 Fab（一种先前已用二硫苏糖醇(DTT)还原的鼠抗黑色素瘤抗体Fab片段）的缀合平均产率为85%。对NR-ML-05 Fab的IPEM缀合物(6)进行的体外化学挑战和血清稳定性研究结果表明，放射性碘形成了稳定的共价连接。在荷瘤无胸腺裸鼠中对IPEM缀合物进行的生物分布研究显示，甲状腺和胃中放射性碘没有明显积累，这表明其在体内具有稳定性。观察到的肿瘤摄取情况与用氯胺-T或对碘苯甲酸酯标记的NR-ML-05 Fab缀合物的摄取情况一致。
