Complementary strategies for developing Gd-free high-field T₁ MRI contrast agents based on Mn(III) porphyrins

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jm401124bMn(III) porphyrin (MnP) holds the promise of addressing the emerging challenges associated with Gd-based clinical MRI contrast agents (CAs), namely, Gd-related adverse effect and decreasing sensitivity at high clinical magnetic fields. Two complementary strategies for developing new MnPs as Gd-free CAs with optimized biocompatibility were established to improve relaxivity or clearance rate. MnPs with distinct and tunable pharmacokinetic properties can consequently be constructed for different in vivo applications at clinical field of 3 T.This work was mainly supported by NSERC through a Discovery Grant awarded to X-a.Z (# 489075). X-a.Z. is also grateful to the University of Toronto Scarborough, Canada Foundation for Innovation, and Ontario Research Fund. H-L.C. is supported by NSERC through a Discovery Grant and by the SickKids Foundation. T.J.S. acknowledges financial support from the Ontario Institute for Cancer Research (Investigator Award) and NSERC (Discovery Grant)