Mechanistic Studies of Gd³⁺‐Based MRI Contrast Agents for Zn²⁺ Detection: Towards Rational Design

Abstract

A series of novel pyridine-based Gd(3+) complexes have been prepared and studied as potential MRI contrast agents for Zn(2+) detection. By independent assessment of molecular parameters affecting relaxivity, we could interpret the relaxivity changes observed upon Zn(2+) binding in terms of variations of the rotational motion.

Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

“…Other zinc-sensing conjugates for Gd 3+ that should be mentioned are pyridine-based ligands. Although these sensors worked in vitro, the authors who introduced these agents concluded that they were not suitable candidates for in vivo use because of their low stability and small, non-monotonic response to Zn 2+ [ 61 ]. In addition to Zn 2+ -responsive Gd 3+ -based MR contrast agents, other approaches have been suggested for detecting Zn 2+ in tissues.…”

Smart MRI Agents for Detecting Extracellular Events In Vivo: Progress and Challenges

“…The first reported agent that could detect Zn 2+ with in vivo application is a manganese porphyrin-derivative, Mn(III)-(DPA-C 2 ) 2 -TPPS 3 , that could detect contrast enhancement in T 1 -weighted images from the hippocampus and the caudate-putamen [40,41]. Subsequently, several gadolinium-based Zn 2+ -responsive CAs have been reported; however, few have made the critical transition from in vitro to in vivo imaging [42][43][44][45]. The typical strategy for zinc-responsive agents is to alter the aminopolycarboxylate macrocyclic ring with a zinc-binding ligand; examples are included in Figure 4.…”

MRI‐based Sensors for In Vivo Imaging of Metal Ions in Biology

“…The relaxivity of the obtained sensor was increased by almost 150 % at high magnetic field B 0 (7.0 T) in the presence of Zn 2+ compared to Ca 2+ and Mg 2+ . Although other strategies for improving Zn 2+ sensing with MRI were proposed, none of the above mentioned sensors have been used in vivo .…”