Cancer Drug Delivery 1984-01-01

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.

J Powe, K Y Pak, C H Paik, Z Steplewski, M A Ebbert, D Herlyn, C Ernst, A Alavi, W C Eckelman, R C Reba

Index: Cancer Drug Deliv. 1(2) , 125-35, (1984)

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Abstract

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.