Labeling of a bifunctional monophosphinic acid DOTA analogue with 111In: Radiochemical aspects and preclinical results
Abstract
The complex formation of the monophosphinic analogue of DOTA bearing 4-aminobenzyl group with (111)In at a trace level was analyzed. Pharmacokinetics and biodistribution of the complex was studied in rats. / 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 (111)In at a tracer level was analyzed.
Formation of a complex between (111)In 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 (111)In-DO3AP(ABn) were separated on HPLC.
Four peaks were separated by HPLC, they probably correspond to four diastereoisomers of (111)In-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.