Transcobalamin II receptor imaging via radiolabeled diethylene-triaminepentaacetate cobalamin analogs

Rapidly dividing cells up-regulate the number of transcobalamin II receptors during DNA replication. We have developed diethylene-triaminepentaacetate (DTPA) cobalamin analogs for the purpose of imaging transcobalamin II receptors in malignant and nonmalignant tissue.

Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs were synthesized. In vitro binding of the analogs to the transcobalamin proteins was assessed by the unsaturated vitamin B12 binding capacity assay and compared to DTPA and cyanocobalamin. The biodistribution of the 111In-DTPA cobalamin analogs was measured at 24 hr after injection into sarcoma-bearing mice and non-tumor-bearing mice and pigs.

Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs and DTPA were 94.0%, 90.4%, 66.4%, and 3.6%, respectively, as efficient in binding to the transcobalamin proteins when compared to cyanocobalamin. At 24 hr after administration, the cobalamin analogs had 5-17 times and 20-29 times, respectively, the amount of uptake within the resected tissue samples and transplanted sarcomas when compared to 111In-DTPA.

The radiolabeled DTPA cobalamin analogs are biologically active. Preliminary animal studies suggest that the analogs could be effective in vivo transcobalamin II receptor imaging agents.