Labeling of a bifunctional monophosphinic acid DOTA analogue with ¹¹¹In: Radiochemical aspects and preclinical results

Abstract

The complex formation of the bifunctional monophosphinic acid DOTA analogue DO3AP^ABn (1,4,7,10-tetraazacyclododecane-4,7,10-triacetic-1-{methyl[(4-aminophenyl)methyl] phosphinic acid}) with ¹¹¹In at a tracer level was analyzed. Formation of a complex between ¹¹¹In and DO3AP^ABn was very rapid even at room temperature and high radiolabeling yields were achieved. As introducing the methylphosphinic acid arm to the DOTA structure generated a chiral centre, more than one peak (probably corresponding to various diastereoisomers) of ¹¹¹In-DO3AP^ABn were separated on HPLC. Four peaks were separated by HPLC, they probably correspond to four diastereoisomers of ¹¹¹In-DO3AP^ABn originating from combination of chirality of complexes of DOTA-like ligands with chirality of coordinated phosphorus atom. Studies in rats showed rapid elimination of radioactivity from the blood and other organs and tissues. The results indicate that DO3AP^ABn represents a promising ligand for radiolabeling of target-specific biomolecules with radiometals.