Radiosynthesis of a 68Ga labeled matrix metalloproteinase inhibitor as a potential probe for PET imaging.

Claesener M, Schober O, Wagner S, Kopka K

Abstract

A matrix metalloproteinase inhibitor based on a barbiturate scaffold was conjugated with a cyclooctyne derivative of the (radio)metal chelator DOTA via strain induced azide alkyne cycloaddition. Subsequent radiolabeling with (68)Ga yielded the corresponding radiometal labeled target compound (68)Ga-4 with a yield of 87% (decay corrected). The target molecule was also synthesized by a second synthesis route, the reaction of a pre-labeled (68)Ga-cyclooctyne-DOTA derivative (68)Ga-1 with an azide bearing barbiturate 3. This approach offers a valuable alternative for providing the desired (68)Ga-radiolabeled target compound. But, in this case, the strain induced cycloaddition of the reported pre-labeled cyclooctyne-DOTA derivative (68)Ga-1 with azides was proven to be slow at room temperature and heating was necessary for acceptable reaction times.