Hansen H J, Jones A L, Sharkey R M, Grebenau R, Blazejewski N, Kunz A, Buckley M J, Newman E S, Ostella F, Goldenberg D M
Immunomedics, Inc., Newark, New Jersey 07103.
Cancer Res. 1990 Feb 1;50(3 Suppl):794s-798s.
This communication presents information on the quality and stability of a new conjugate of 99mTc to an anticancer antibody fragment and results of animal imaging and distribution studies. Clinical studies have proved that this labeled antibody can image tumors within 2 hours of i.v. injection. It is produced using an "instant kit," merely requiring addition of [99mTc]pertechnetate to a lyophilized vial containing the fragment and a pertechnetate-reducing agent. Within 5 min of addition of pertechnetate to the vial containing the fragment, [99mTc]pertechnetate is reduced and quantitatively bound to an intrinsic high-affinity receptor present in the Fab'. The Fab'-bound 99mTc is completely stable to challenge with diethylenetriaminepentaacetic acid and human serum albumin. Minimal oxidation and release of 99mTc bound to the fragment were observed when the labeled fragment was incubated for 24 h at 37 degrees C. Animal biodistribution studies were consistent with the known metabolic elimination of a radiolabeled Fab' fragment by the kidney. Tumor localization studies in athymic nude mice bearing xenografts of human colonic carcinoma (GW-39) predicted the positive results later demonstrated in clinical studies.
本通讯介绍了一种新的99mTc与抗癌抗体片段偶联物的质量和稳定性信息，以及动物成像和分布研究结果。临床研究证明，这种标记抗体在静脉注射后2小时内即可对肿瘤进行成像。它是使用“即时试剂盒”生产的，只需将高锝[99mTc]酸盐添加到含有片段和高锝酸盐还原剂的冻干小瓶中。在向含有片段的小瓶中添加高锝酸盐后5分钟内，高锝[99mTc]酸盐被还原并定量结合到Fab'中存在的固有高亲和力受体上。与Fab'结合的99mTc对二乙三胺五乙酸和人血清白蛋白的攻击完全稳定。当标记片段在37℃下孵育24小时时，观察到与片段结合的99mTc的氧化和释放极少。动物生物分布研究与肾脏对放射性标记的Fab'片段的已知代谢清除情况一致。在携带人结肠癌（GW - 39）异种移植瘤的无胸腺裸鼠中进行的肿瘤定位研究预测了后来临床研究中显示的阳性结果。
