BackgroundManganese porphyrins have several therapeutic/imaging applications, including their use as radioprotectants (in clinical trials) and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) radionuclide52Mn (t1/2= 5.6 d) would allow long-termin vivobiodistribution studies of Mn-porphyrins, as well as a method to label and track cells/liposomes, but methods for fast and efficient radiolabelling are lacking.ResultsSeveral porphyrins were produced and radiolabelled by addition to neutralised [52Mn]MnCl2and heating using a microwave (MW) synthesiser, and compared with non-MW heating. MW radiosynthesis allowed >95 % radiochemical yields (RCY) in just 1 h. Conversely, non-MW heating at 70 °C for 1 h resulted in low RCY (0–25 % RCY) and most porphyrins did not reach radiolabelling completion after 24 h. Formation of the52Mn-complexes were confirmed with radio-HPLC by comparison with their non-radioactive55Mn counterparts. Following this, several [52Mn]Mn-porphyrins were used to radiolabel liposomes resulting in 75–86 % labelling efficiency (LE). Two lead [52Mn]Mn-porphyrins were taken forward to label MDA-MB-231 cancer cellsin vitro, achievingca.11 % LE. After 24 h, 32–45 % of the [52Mn]Mn-porphyrins was retained in cells.ConclusionsIn contrast to standard methods, MW heating allows the fast synthesis of [52Mn]Mn-porphyrins with >95 % radiochemical yields that avoid purification. [52Mn]Mn-porphyrins also show promising cell/liposome labelling properties. Our reported technique can potentially be exploited for thein vivoimaging of Mn-porphyrin therapeutics, as well as for the accuratein vivoquantification of Mn-porphyrin MRI agents.