Otsuji E, Yamaguchi T, Yamaoka N, Kotani T, Kato M, Taniguchi K, Kiyamura K, Takahashi T
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Pancreas. 1995 Apr;10(3):265-73. doi: 10.1097/00006676-199504000-00008.
Much recent research has focused on the use of monoclonal antibodies (MAbs) in the immunodetection of solid tumors. Fab fragments of MAbs are more suitable for immunoscintigraphy than intact MAbs. Recently, human-mouse chimeric antibodies have been developed in an effort to reduce human antimouse antibody (HAMA) production by murine MAbs in humans. In this study, 125I-labeled murine and chimeric Fab fragments of the MAb A7 were injected i.v. into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft. The radioactivity in tumors and in normal tissues was subsequently measured. The tumor tissue/blood ratio (T/B) of 125I-labeled murine and chimeric Fab fragments of MAb A7 increased with time in a similar manner and reached 9.68 +/- 2.54 and 10.49 +/- 1.50, respectively, 24 h after injection. Moreover, the T/Bs of 125I-labeled murine and chimeric Fab fragments of MAb A7 were greater than the T/B of intact MAb A7. When mice bearing tumors that did not react with MAb A7 were studied, 125I-labeled murine and chimeric Fab fragments did not localize specifically to the tumors. These results suggests that chimeric Fab fragments of MAb A7 are useful carriers of radionuclides for the immunodetection of human pancreatic cancer, with equivalent activity to murine Fab fragments and less theoretical potential to induce a HAMA response.
近期许多研究聚焦于单克隆抗体（MAb）在实体瘤免疫检测中的应用。与完整单克隆抗体相比，单克隆抗体的Fab片段更适合免疫闪烁成像。最近，人们开发了人鼠嵌合抗体，以减少鼠源单克隆抗体在人体内产生人抗鼠抗体（HAMA）。在本研究中，将125I标记的鼠源和嵌合单克隆抗体A7的Fab片段静脉注射到携带人胰腺癌（HPC-YS）异种移植瘤的裸鼠体内。随后测量肿瘤和正常组织中的放射性。注射后24小时，125I标记的鼠源和嵌合单克隆抗体A7的Fab片段的肿瘤组织/血液比（T/B）以相似的方式随时间增加，分别达到9.68±2.54和10.49±1.50。此外，125I标记的鼠源和嵌合单克隆抗体A7的Fab片段的T/B大于完整单克隆抗体A7的T/B。当研究携带不与单克隆抗体A7反应的肿瘤的小鼠时，125I标记的鼠源和嵌合Fab片段未特异性定位于肿瘤。这些结果表明，单克隆抗体A7的嵌合Fab片段是用于人胰腺癌免疫检测的放射性核素的有用载体，其活性与鼠源Fab片段相当，且诱导HAMA反应的理论可能性较小。
