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

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 68Ga yielded the corresponding radiometal labeled target compound 68Ga-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 68Ga-cyclooctyne-DOTA derivative 68Ga-1 with an azide bearing barbiturate 3. This approach offers a valuable alternative for providing the desired 68Ga-radiolabeled target compound. But, in this case, the strain induced cycloaddition of the reported pre-labeled cyclooctyne-DOTA derivative 68Ga-1 with azides was proven to be slow at room temperature and heating was necessary for acceptable reaction times.

► Synthesis of a 68Ga-labeled matrix metalloproteinase inhibitor.
► Post- and pre-labeling approaches were conducted and compared to each other.
► A 68Ga-pre-labeled cyclooctyne derivative was provided for labeling azides directly.