CLINICAL TRIALS WITH RADIOLABELED ANTIBODIES

对原发灶和转移灶的准确检测和解剖定位 损伤仍然是大多数人类管理中的主要问题之一 癌症。我们最近在NIH临床中心启动了临床试验 中心使用以下技术检测和定位结直肠癌病变 放射性标记单抗B72.3。参数将被系统化 研究了单抗本地化的效率和 癌症病变的伽马扫描的效率包括：(A) 放射性核素偶联单抗的剂量和比活度；(B)比较 使用完整的IgG、F(ab‘)2和Fab’；(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 肿瘤的肿块，如抗原含量；(F)循环的存在 抗原；(G)人抗鼠免疫球蛋白的存在和/或不存在 抗体；(H)单抗和片段的代谢；(I)单抗的结合。 希望这些研究也将有助于建立一个理性的 为特定单抗的后续治疗使用奠定了基础 通过效应细胞介导或补体介导与毒素偶联 机制，或使用放射性标记多种同位素之一的单抗。 后一个目标可以通过对活检材料的直接分析来实现 (包括肿瘤和正常组织)从接受放射性标记的单抗到 定义“放射定位指数”或潜在的“治疗指数” (即，每克肿瘤通过CPM结合的单抗的量的比率 每克正常组织的结合量)。

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).