Gd-Free MRI Contrast Agents Based on Mn-Porphyrin
Current clinical MRI contrast agents (CAs) are predominantly based on gadolinium (Gd3+) complexes. With a high paramagnetic dipole moment, relatively long electron relaxation time, and a large ionic radius to form stable multidentate chelate, Gd3+ has been a preferred and obvious choice for the development of MRI CAs. The NMR paramagnetic relaxation enhancement properties of Gd T1 agents have been well studied, as summarized in the classic Solomon, Bloembergen and Morgan (SBM) model. Challenges remain however, since conventional Gd-chelates exhibit lower-than-anticipated T1 relaxivity, especially at high clinical field of 3T, and sub-optimal stability, restricting the applications for future targeted molecular or cellular imaging. In this talk, I will present our efforts on the development of Gd-free CAs based on Mn3+-porphyrin (MnP). Despite the fact Mn3+ has only 4 unpaired electrons, in contrast to 7 for Gd3+ and 5 for Mn2+, rationally designed MnPs could achieve higher T1 relaxivity, especially at high clinic fields. Furthermore, as synthetic metal-ligand complex, MnP is remarkably more stable against metal dissociation or transmetallation in vitro and in vivo, even though Mn3+ is a relatively small metal ion. I will highlight our challenges to use the existing relaxation model to interpret these desirable yet “abnormal” behaviors of MnP as potentially better MRI T1 agent. Finally, the advantages of MnP for constructing next generation molecular/cellular imaging probes, will be summarized.