Evaluation of the [formula omitted] monoclonal antibody and the use of technetium-99m-labeled [formula omitted] Fab′ for the detection of pan adenocarcinoma

Abstract

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 × 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 l 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.