CLINICAL TRIALS WITH RADIOLABELED ANTIBODIES

准确检测和解剖定位原发灶和 转移性病变仍然是乳腺癌的主要问题之一。 大多数人类癌症的管理。我们最近发起了 在NIH临床中心和其他几个中心进行的临床试验 合作机构检测和定位癌症病变 使用放射性标记的单抗(MAb)B72.3。参数 正在进行系统的调查，涉及的是 单抗定位的效率和伽马扫描的效率 癌损害的影响包括：(A)单抗剂量和特异性 放射性核素偶联单抗的活性；(B)肿瘤类型 (C)放射性核素的选择；(D) 接种途径；(E)大小、位置和其他固有的 肿瘤性质，如抗原含量；(F) 循环抗原的存在；(G)存在和/或 人源性抗鼠Ig抗体的研制；(H)新陈代谢 Mab.希望这些研究也将有助于建立 为随后的特定治疗使用提供合理的基础 单抗，通过效应细胞介导与毒素偶联，或 补体介导的机制，或使用标记有补体的单抗 不同的同位素。后一个目标可以通过以下方式实现 活检材料(肿瘤和正常组织)的直接分析 从接受放射性标记的单抗的患者中确定 “放射定位指数”或潜在的“治疗指数”(即， 每克肿瘤的单抗结合量(通过CPM)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 and several other collaborating institutions to detect and localize carcinoma lesions using radiolabeled monoclonal antibody (MAb) B72.3. Parameters that are being 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) type of carcinoma (colorectal, ovarian, lung, breast) (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 development of human anti-murine Ig antibodies; (h) metabolism of MAb. 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).