Hadley S W, Wilbur D S
NeoRx Corporation, Seattle, Washington 98119.
Bioconjug Chem. 1990 Mar-Apr;1(2):154-61. doi: 10.1021/bc00002a011.
The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-[125I/131I]iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-[125I/131I]iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-[131I]iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was approximately a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate.
报道了2,3,5,6-四氟苯基5-[¹²⁵I/¹³¹I]碘代-4-戊烯酸酯（7a）和2,3,5,6-四氟苯基3,3-二甲基-5-[¹²⁵I/¹³¹I]碘代-4-戊烯酸酯（7b）与单克隆抗体的制备及偶联情况。试剂7a和7b通过其相应的5-三正丁基锡前体的碘脱锡反应以高放射化学产率制备。放射性碘标记的抗体偶联物通过在碱性pH条件下使7a或7b与蛋白质反应来制备。通过几种体外方法对这些偶联物进行评估表明，放射性标记以稳定的方式连接到抗体上，并且偶联物保持免疫反应性。已在荷瘤裸鼠中进行了7a和7b的单克隆抗体Fab片段偶联物与用N-琥珀酰亚胺基对-[¹³¹I]碘苯甲酸酯（PIB，对碘苯甲酸酯，2）标记的相同Fab片段或直接放射性碘标记的Fab片段的比较双同位素生物分布研究。7a的Fab偶联物与2的Fab偶联物共同注射表明，除颈部组织（含甲状腺）和胃外，大多数器官中的生物分布相似，颈部组织和胃中7a标记物的含量显著增加。7a的Fab偶联物与用氯胺-T法放射性碘标记的Fab片段共同注射表明，生物分布非常相似，这表明这些标记的抗体片段在体内的脱碘情况大致相当。7a的Fab偶联物与7b的Fab偶联物共同注射表明，与7a偶联物相比，7b偶联物在体内的脱碘量大约减少了2倍。
