INTRODUCTION OF 5 POTENTIALLY METABOLIZABLE LINKING GROUPS BETWEEN IN-111 CYCLOHEXYL EDTA DERIVATIVES AND F(AB')2 FRAGMENTS OF ANTICARCINOEMBRYONIC ANTIGEN-ANTIBODY .2. COMPARATIVE PHARMACOKINETICS AND BIODISTRIBUTION IN HUMAN COLORECTAL CARCINOMA-BEARING NUDE-MICE

The five linker-containing immunoconjugates described in the preceding paper were labeled with In-111 and tested for their biodistribution, pharmacokinetics and immunoscintigraphic tumor-xenografted nude mice. The results were compared with DTPADA and CDTAMA for reference. Result s showed that, for immunoscintigraphy, the derivatives in decreasing o rder of effectiveness were: aliphatic (tumor/liver > 4.5 and tumor/kid ney > 6.5 at 96 h), thioether (tumor/liver > 3 and tumor/kidney > 1.2 at 24 h), ethylene glycol succinate (tumor/liver > 1.7 and tumor/kidne y > 0.5 at 24 h) and disulfide (tumor/liver > 0.5 and tumor/kidney > 0 .6 at 96 h). Pharmacokinetic results were complementary with those of the biodistribution studies and provide a basis for the study of in vi vo metabolic mechanisms of linker-immunoconjugates. Indium-111-labeled linker-immunoconjugates appear promising for tumor imaging with bette r contrast than what is obtained with the use of the conventional In-1 11-DTPA dianhydride chelate.