Issue 3, 2022

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

Abstract

A new potential ZnII responsive MnII-based MRI CA candidate derived from pyclen-3,9-diacetate (3,9-PC2A) has been synthesized and it possesses a di-(2-picolyl)amine (DPA) moiety as an active arm. The PC2A-DPA ligand was found to form a thermodynamically stable complex with MnII (log KMnL = 15.87(6) which translates into a pMn of 8.79) which also possesses outstanding inertness towards ZnII ion triggered transmetallation (t1/2 at pH = 6.0 is 64.5 h). The [Mn(PC2A-DPA)] complex has a relatively high relaxation rate (3.11 s−1 at 1.41 T and 37 °C for a 0.96 mM complex) which is not affected by the ZnII concentration directly, yet in the co-presence of 0.7 mM human serum albumin (HSA) the relaxation rate values (both R1 and R2) increased significantly (9.08 s−1 at 1.41 T and 37 °C, for a 0.748 mM complex) 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 using phantoms in vitro while preliminary in vivo MRI experiments confirmed that the glucose stimulated ZnII secretion (GSZS) can be visualized in the prostate of a healthy mouse.

Graphical abstract: Synthesis and characterization of a stable and inert MnII-based ZnII responsive MRI probe for molecular imaging of glucose stimulated zinc secretion (GSZS)

Supplementary files

Article information

Article type
Research Article
Submitted
16 apr 2021
Accepted
06 dec 2021
First published
09 dec 2021

Inorg. Chem. Front., 2022,9, 577-583

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

R. Botár, E. Molnár, Z. Garda, E. Madarasi, G. Trencsényi, J. Kiss, F. K. Kálmán and G. Tircsó, Inorg. Chem. Front., 2022, 9, 577 DOI: 10.1039/D1QI00501D

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