In vivo instability of reduction-mediated 99mTc-labeled monoclonal antibody

A murine monoclonal antibody that reacts with human osteogenic sarcoma (OST7) was reduced and directly labeled with 99mTc without any loss of immunoreactivity. No fragmentation of the antibody was detected by high performance liquid chromatography after the labeling. However, SDS-PAGE analysis of the labeled antibody demonstrated the presence of low molecular weight species. Although more than 95% of the radioactivity remained bound at the antibody after incubation with human serum for 24 h, 99mTc-labeled OST7 was cleared faster from the circulation than 125I-labeled OST7 or 111In-labeled OST7 in mice. Urinary and fecal excretion of 99mTc were higher than those of 125I. When the 125I-labeled antibody was dual-labeled with 99mTc, the blood clearance of 99mTc was faster than that of 125I, suggesting release of 99mTc from the antibody in vivo. 99mTc-labeled OST7, however, gave a higher tumor-to-blood ratio than 125I- or 111In-labeled OST7 in mice bearing human osteogenic sarcoma. The 99mTc-labeled antibody prepared by the direct method was unstable in vivo, but retained a good tumor targeting ability.