Lange M K, Sandhu A, Sampsel J, Hinkle G, Ignaszewski J, Martin E, Sandhu P, Martin E W
Department of Surgery, Ohio State University College of Medicine, Columbus 43210.
J Surg Res. 1993 Aug;55(2):205-13. doi: 10.1006/jsre.1993.1131.
The Neoprobe Model 1000 hand-held gamma detector, in combination with the murine monoclonal antibody (MAb) B72.3 can successfully intraoperatively target both primary and recurrent colorectal cancer. Because of the shortcomings of this system (length of time needed to clear unbound MAb and heterogeneous staining of cancer cells), new MAbs are under investigation. NR-LU-10 IgG and its FAB fragment were evaluated with the Neoprobe gamma detector in a nude mouse model. NR-LU-10 is a pancarcinoma IgG2b antibody that recognizes an oncofetal glycoprotein antigen that is expressed by most carcinomas. Animals were injected intraperitoneally with 125I-labeled IgG, 125I, or technetium 99m (99mTc)-labeled Fab fragment. The Neoprobe gamma detector and standard gamma well counts provided biodistribution and pharmacokinetic data. The Fab fragment achieved a 5:1 tumor to blood-pool background (BPB) ratio in only 66 hr, whereas the whole MAb required 14 days. Technetium did not appear to be an adequate isotope for this system because of its short half-life. Autoradiographs performed for both the 125I-labeled NR-LU-10 IgG and its 125I-labeled Fab fragment (but not 99mTc-labeled Fab) localized well in this model and gave adequate tumor to BPB and tissue ratios. Use of the 125I-labeled Fab significantly decreased the time required for clearance of the MAb radionuclide complex from the blood and tissue background, thus providing earlier tumor localization in the Radioimmunoguided Surgery (RIGS) system.
Neoprobe 1000型手持式γ探测器与鼠源单克隆抗体（MAb）B72.3联合使用，可在术中成功靶向原发性和复发性结直肠癌。由于该系统存在缺陷（清除未结合单克隆抗体所需时间长以及癌细胞染色不均一），新型单克隆抗体正在研究中。在裸鼠模型中，使用Neoprobeγ探测器对NR-LU-10 IgG及其FAB片段进行了评估。NR-LU-10是一种泛癌IgG2b抗体，可识别大多数癌表达的一种癌胚糖蛋白抗原。给动物腹腔注射125I标记的IgG、125I或锝99m（99mTc）标记的FAB片段。Neoprobeγ探测器和标准γ计数管提供了生物分布和药代动力学数据。FAB片段仅在66小时内就实现了肿瘤与血池本底（BPB）5:1的比值，而完整单克隆抗体则需要14天。由于半衰期短，锝似乎不是该系统适用的同位素。对125I标记的NR-LU-10 IgG及其125I标记的FAB片段（而非99mTc标记的FAB）进行的放射自显影在该模型中定位良好，肿瘤与BPB及组织的比值也合适。使用125I标记的FAB显著缩短了单克隆抗体放射性核素复合物从血液和组织本底清除所需的时间，从而在放射免疫导向手术（RIGS）系统中实现了更早的肿瘤定位。
