Kitamura K, Takahashi T, Noguchi A, Tsurumi H, Takashina K, Okuzumi J, Yamaguchi T
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Tohoku J Exp Med. 1991 Jul;164(3):203-11. doi: 10.1620/tjem.164.203.
The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.
在将鼠单克隆抗体A7与新制癌菌素（A7-NCS）的二硫键连接共轭物静脉注射给裸鼠后，研究了其药代动力学。共轭物从循环中的消失呈双相性：早期快速阶段之后是一个慢得多的阶段。共轭物从血液循环中清除的半衰期为12小时，显示出与游离抗体几乎相同的动力学。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析表明，在将共轭物注射给裸鼠后，A7-NCS中的二硫键至少在48小时内是稳定的。源自人结肠癌SW1116的肿瘤中的共轭物浓度在注射后24小时达到最大值，并在另外24小时内保持高位。被动血凝抑制试验表明，共轭形式的NCS可以有效地递送至靶组织。本报告表明，A7-NCS在循环中足够稳定，能够在不释放NCS的情况下到达靶肿瘤。
