Wada K, Watanabe T, Tadokoro M, Sakamoto J, Murayama H, Sakuma S, Takagi H
Second Department of Surgery, Nagoya University School of Medicine, Japan.
Nihon Geka Gakkai Zasshi. 1992 Mar;93(3):266-73.
In order to improve cancer imaging with radiolabeled antibodies, three factors appeared to be of particular importance: (1) The selection of the most favorable monoclonal antibody directed to tumor-associated antigen. (2) The use of F(ab')2 or Fab fragments. (3) Selection of the most convenient isotope. Monoclonal antibody CEA 102 was produced by immunization by purified CEA, and its F(ab')2 fragments were compared with whole IgG as a radiotracer for radioimmunodetection of the colorectal cancer. Fragments were eliminated from the circulation twice as fast as whole IgG, and tumor-to-background ratio was achieved more than 1 at 2-3 days with F(ab')2, but 6-7 days with whole IgG in tumor bearing nude mice. In clinical study, F(ab')2 demonstrated clear image on the 1 at day after injection, whereas achievement of the image was possible on the 3rd day in whole IgG. These results indicated that fragments are preferred over whole IgG. Therefore fragments make it possible to preclude dual isotope subtraction methods, and omit the long delays before imaging. They also make it possible to use short half life radionuclides with excellent photon properties, such as 123I and 99mTc.
为了利用放射性标记抗体改善癌症成像,有三个因素显得尤为重要:(1)选择针对肿瘤相关抗原的最适宜单克隆抗体。(2)使用F(ab')2或Fab片段。(3)选择最便利的同位素。通过用纯化的癌胚抗原(CEA)免疫制备了单克隆抗体CEA 102,并将其F(ab')2片段与完整IgG作为放射性示踪剂用于结直肠癌的放射免疫检测进行比较。片段从循环中清除的速度比完整IgG快两倍,在荷瘤裸鼠中,F(ab')2在2 - 3天时肿瘤与背景比值超过1,而完整IgG则需6 - 7天。在临床研究中,F(ab')2在注射后第1天显示出清晰图像,而完整IgG在第3天才有可能成像。这些结果表明片段比完整IgG更具优势。因此,片段使得无需采用双同位素减法方法,并且省去成像前的长时间延迟。它们还使得使用具有优异光子特性的短半衰期放射性核素成为可能,如123I和99mTc。