CLINICAL TRIALS WITH RADIOLABELED ANTIBODIES

原发灶和转移灶的准确检测和解剖定位 病变仍然是大多数人的管理中的主要问题之一 癌 我们最近在美国国立卫生研究院临床实验室 中心检测和定位结直肠癌病变使用 放射性标记的MAb B72.3。 这些参数将被系统地 研究了单克隆抗体定位的效率和 癌病变的伽马扫描的效率包括：（a） 放射性核素偶联MA B的MA B剂量和比活度;（B）比较 完整IgG、F（ab '）2和Fab'的使用;（c）放射性核素的选择; (d)接种途径;（e）大小、位置和其他固有特性 （f）肿瘤组织中的抗原含量; 抗原;（g）存在和/或不存在人抗鼠IG 抗体;（h）单克隆抗体和片段的代谢;（i）单克隆抗体的组合。 希望这些研究也有助于建立一个合理的 特定MAb后续治疗用途的基础， 通过效应细胞介导的或补体介导的 机制，或使用用多种同位素之一放射性标记的单克隆抗体。 后一个目标可以通过直接分析活检材料来实现 (both肿瘤和正常组织）， 定义“放射定位指数”或潜在的“治疗指数” (i.e.,每克肿瘤结合的MAb量[通过cpm]的比率 组织与每克正常组织的结合）。

Accurate detection and anatomic localization of both primary and metastatic lesions remains one of the major problems in the management of most human carcinomas. We have recently initiated clinical trials at the NIH Clinical Center to detect and localize colorectal carcinoma lesions using radiolabeled MAb B72.3. Parameters that will be systematically investigated concerning both the efficiency of MAb localization and the efficiency of gamma scanning of carcinoma lesions include: (a) effect of MAb dose and specific activity of radionuclide coupled MAb; (b) comparison of the use of intact IgG, F(ab')2, and Fab'; (c) choice of radionuclide; (d) route of inoculation; (e) size, location, and other inherent properties of the tumor mass such as antigen content; (f) the presence of circulating antigen; (g) the presence and/or absence of human anti-murine Ig antibodies; (h) metabolism of MAb and fragments; (i) combiantions of MAbs. It is hoped that these studies will also aid in establishing a rational basis for the subsequent therapeutic use of a particular MAb, either coupled to toxins, via effector cell-mediated or complement-mediated mechanisms, or using MAbs radiolabeled with one of a variety of isotopes. This latter goal can be accomplished by direct analyses of biopsy material (both tumor and normal tissues) from patients receiving radiolabeled MAb to define the "radiolocalization index" or potential "therapeutic index" (i.e., the ratio of the amount of MAb bound [via cpm] per gram of tumor tissue to that bound per gram of normal tissues).