McQuarrie S A, Baum R P, Golberg L, Niesen A, Golberg K, Noujaim A A, McEwan A J
Cross Cancer Institute, Edmonton, Canada.
J Nucl Biol Med (1991). 1994 Dec;38(4 Suppl 1):140-4.
The monoclonal antibody (MoAb) 174H.64 (Truscint SQ, Biomira Inc.) is a murine-derived MoAb reacting with an extracellular surface component of the cytoskeletal matrix ectopically expressed on squamous-cell carcinoma cell-surface membranes. A chimeric form of this MoAb has also been produced by genetically modifying the Fc portion of the MoAb by the insertion of a human Fc fragment. During this process the isotype was altered from an IgG1 (murine) to an IgG3 (chimeric). Pilot and phase I/II clinical trials of the murine and chimeric 99mTc-labelled 174H.64 MoAbs have been undertaken at selected European and North American sites. As part of this evaluation serum, urine and image data were collected at specific time intervals and used to obtain a kinetic model to describe the in vivo distribution of the MoAbs. A two-compartment model of the form: C(t) = C1 e-lambda 1t + Cz e-lambda zt was found to best describe the serum distribution of radioactivity of both the murine and chimeric MoAbs. The initial distribution half-lives were 2.9 +/- 0.7 hours and 2.7 +/- 0.2 hours, and the terminal elimination half-lives were 17.6 +/- 3.8 hours and 22.5 +/- 1.3 hours for the murine and chimeric MoAbs, respectively. No significant difference was found between the kinetic model parameters of two MoAbs at the 95% level. Assuming a similar clinical efficacy, these MoAbs could then be used interchangeably, with the chimeric MoAb offering potential advantages in reducing HAMA response.
单克隆抗体（MoAb）174H.64（Truscint SQ，Biomira公司）是一种源自小鼠的单克隆抗体，可与鳞状细胞癌细胞表面膜上异位表达的细胞骨架基质的细胞外表面成分发生反应。通过插入人Fc片段对该单克隆抗体的Fc部分进行基因改造，还产生了这种单克隆抗体的嵌合形式。在此过程中，同种型从IgG1（小鼠）变为IgG3（嵌合）。已在选定的欧洲和北美地点对小鼠和嵌合的99mTc标记的174H.64单克隆抗体进行了先导试验和I/II期临床试验。作为该评估的一部分，在特定时间间隔收集血清、尿液和图像数据，并用于获得动力学模型，以描述单克隆抗体在体内的分布。发现形式为：C(t)=C1e-lambda 1t + Cz e-lambda zt的双室模型最能描述小鼠和嵌合单克隆抗体的放射性血清分布。小鼠和嵌合单克隆抗体的初始分布半衰期分别为2.9±0.7小时和2.7±0.2小时，终末消除半衰期分别为17.6±3.8小时和22.5±1.3小时。在95%水平上，两种单克隆抗体的动力学模型参数之间未发现显著差异。假设具有相似的临床疗效，那么这些单克隆抗体可以互换使用，嵌合单克隆抗体在降低人抗鼠抗体（HAMA）反应方面具有潜在优势。
