Synthesis and characterization of a stable and inert Mn-II-based Zn-II responsive MRI probe for molecular imaging of glucose stimulated zinc secretion (GSZS)

A new potential Zn(II) responsive Mn(II)-based MRI CA candidate derived form pyclen-3,9-diacetate (3,9-PC2A) has been synthesized possessing a di-(2-picolyl)amine (DPA) moiety as an active arm. The PC2A-DPA ligand was found to form thermodynamically stable complex with Mn(II) (log KMnL=15.87(6) which translate into pMn of 8.79) which also posses an outstanding inertness towards Zn(II) ion triggered transmetallation (t1/2 at pH=6.0 is 64.5 h). The [Mn(PC2A-DPA)] complex has relatively high relaxivity (3.24 mM-1s-1 at 1.41 T and 37 oC) which is not affected by Zn(II) concentration directly, yet in the co-presence of Human Serum Albumin (HSA) relaxivity values (both r1p and r2p) increased significantly (12.14 mM-1s-1 at 1.41 T and 37 oC) owing to the efficient binding of the complex to the protein (log Kaff=3.5±0.1 M-1). The increase is large enough to visualize it by MR imaging on phantoms in vitro while in vivo MRI experiments confirmed that the glucose stimulated Zn(II) secretion (GSZS) can be visualized in a prostate of healthy mice