Pak K Y, Nedelman M A, Fogler W E, Tam S H, Wilson E, Van Haarlem L J, Colognola R, Warnaar S O, Daddona P E
Research and Development Division, Centocor, Inc., Malvern, PA 19355.
Int J Rad Appl Instrum B. 1991;18(5):483-97. doi: 10.1016/0883-2897(91)90109-x.
The 323/A3 murine monoclonal antibody, initially described as reactive to breast carcinomas, is found by immunohistological analyses to have broad cross reactivity with adenocarcinomas of diverse histologic origin. The 323/A3 antigen is similar to the tumor-associated 17-1A antigen as revealed by immunoblot and cross-competition cell binding studies. We have investigated the potential use of the 323/A3 monoclonal antibody for tumor imaging as a Fab' molecule labeled with 99mTc. In vitro studies demonstrate that 323/A3 Fab' has high affinity (2-3 x 10(9) M-1) with no significant loss of immunoreactivity compared to the intact IgG. In vivo studies demonstrate that 99mTc 323/A3 Fab' can rapidly detect human breast and colon tumor xenografts growing in athymic nude mice. Distinct breast tumor visualization is observed as early as 1 h post intravenous administration with the 99mTc 323/A3 Fab'. Distinct colon tumor visualization is observed by 3 h (the earliest time point imaged). Tumor-to-blood ratios are higher for 99mTc 323/A3 Fab' than with a 99mTc-labeled nonspecific isotype-matched Fab' antibody. These results suggest that 99mTc 323/A3 Fab' can detect 17-1A antigen and may have potential clinical utility for the rapid diagnostic imaging of adenocarcinomas.
323/A3鼠单克隆抗体最初被描述为对乳腺癌有反应，通过免疫组织学分析发现它与多种组织学来源的腺癌具有广泛的交叉反应性。免疫印迹和交叉竞争细胞结合研究表明，323/A3抗原与肿瘤相关的17-1A抗原相似。我们研究了用99mTc标记的Fab'分子形式的323/A3单克隆抗体在肿瘤成像中的潜在用途。体外研究表明，与完整的IgG相比，323/A3 Fab'具有高亲和力（2 - 3×10⁹ M⁻¹），且免疫反应性无明显丧失。体内研究表明，99mTc 323/A3 Fab'能快速检测无胸腺裸鼠体内生长的人乳腺和结肠肿瘤异种移植物。静脉注射99mTc 323/A3 Fab'后1小时即可观察到明显的乳腺肿瘤显像。在3小时（成像的最早时间点）可观察到明显的结肠肿瘤显像。99mTc 323/A3 Fab'的肿瘤与血液比值高于99mTc标记的非特异性同型匹配Fab'抗体。这些结果表明，99mTc 323/A3 Fab'能检测17-1A抗原，可能对腺癌的快速诊断成像具有潜在的临床应用价值。
