Takashina K, Kitamura K, Yamaguchi T, Noguchi A, Noguchi A, Tsurumi H, Takahashi T
First Department of Surgery, Kyoto Prefectural University of Medicine.
Jpn J Cancer Res. 1991 Oct;82(10):1145-50. doi: 10.1111/j.1349-7006.1991.tb01769.x.
The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.
鼠单克隆抗体A7（Mab A7）用几种大分子进行了化学修饰：葡聚糖、聚乙二醇和抗癌多肽新制癌菌素。随后检测了这些组合的药代动力学特性。放射免疫分析表明，所有制剂均保留了其抗原结合活性。Mab A7-新制癌菌素缀合物从血液循环中清除的动力学模式与亲本Mab A7几乎相同。在这三种制剂中，Mab A7-葡聚糖（A7-Dx）从循环中清除得最快。Mab A7-聚乙二醇（A7-PEG）的血药清除曲线最慢，其在循环中的半衰期是亲本Mab A7的两倍。在正常器官分布中，以组织：血液比值表示时，A7-Dx在肝脏、脾脏和肾脏中的摄取最高，而A7-PEG的摄取最低。尽管A7-Dx在肿瘤中的摄取较低，但在荷瘤裸鼠中，这三种缀合物之间没有显著差异。由于A7-PEG具有高血药滞留率但低正常器官摄取率，它似乎是使用抗体进行靶向癌症治疗的良好候选物。
