Biodistribution in tumour-bearing mice of two Y-90-labelled biotins using three-step tumour targeting

Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (Y-90) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of Y-90 through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of Y-90 bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and Y-90-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of Y-90 was observed in animals administered Y-90-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of Y-90-DTPA-biotin. Despite the lower levels of accumulation in the tumour after injection of Y-90-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of Y-90-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal Y-90-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.