Introduction of five potentially metabolizable linking groups between 111In-cyclohexyl EDTA derivatives and F(ab')2 fragments of anti-carcinoembryonic antigen antibody--II. Comparative pharmacokinetics and biodistribution in human colorectal carcinoma-bearing nude mice.

The five linker-containing immunoconjugates described in the preceding paper were labeled with 111In and tested for their biodistribution, pharmacokinetics and immunoscintigraphic imaging properties in tumor-xenografted nude mice. The results were compared with DTPADA and CDTAMA for reference. Results showed that, for immunoscintigraphy, the derivatives in decreasing order of effectiveness were: aliphatic (tumor/liver > 4.5 and tumor/kidney > 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/kidney > 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 vivo metabolic mechanisms of linker-immunoconjugates. Indium-111-labeled linker-immunoconjugates appear promising for tumor imaging with better contrast than what is obtained with the use of the conventional 111In-DTPA dianhydride chelate.