CLINICAL TRIALS WITH RADIOLABELED ANTIBODIES

原发性和非原发性肿瘤的准确检测和解剖定位 转移性病变仍然是癌症治疗中的主要问题之一， 管理大多数人类癌症。 我们最近发起了 NIH临床中心和其他几个临床试验 合作机构检测和定位癌病变 使用放射性标记的单克隆抗体（MAb）B72.3。 参数 正在进行系统的调查， 单克隆抗体定位效率和γ扫描效率 包括：（a）MAb剂量和特异性 放射性核素偶联MA B活性;（B）型癌 （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 肿瘤块的性质，如抗原含量;（f）肿瘤块的性质，如抗原含量; （g）循环抗原的存在; 人抗鼠IG抗体的开发;（h） mAb. 希望这些研究也有助于建立 一个合理的基础，随后的治疗使用的特定 单克隆抗体，通过效应细胞介导或 补体介导的机制，或使用单克隆抗体放射性标记的一个 各种同位素的混合物。 后一个目标可以通过以下方式实现： 直接分析活检材料（肿瘤和正常组织） 从接受放射性标记单克隆抗体的患者中， “放射定位指数”或潜在的“治疗指数”（即， 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 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).