Labeling monoclonal antibodies and F(ab')2 fragments with (111In) indium using cyclic DTPA anhydride and their in vivo behavior in mice bearing human tumor xenografts.

Monoclonal antibodies (MAb) and their F(ab')2 fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2 fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The 111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with 131I. F(ab')2 labeled with 111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with 131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using 131I-labeled F(ab')2 3 days after injection, it was difficult to visualize tumor grafts with 111In-labeled F(ab')2 due to persistently high renal, liver, and background activity. Increased catabolism of the 131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity for in vivo imaging studies before firm conclusions can be drawn.