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Design Strategies for Responsive Fluorine‐19 Magnetic Resonance Probes Using Paramagnetic Metal Complexes

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Responsive fluorine (19F) MRI agents can be created by using paramagnetic metals that quench or perturb the 19F signal of the coordinated fluorinated ligand. Through careful ligand design, these agents can interact with analytes and abnormal cellular conditions to change their magnetic properties to produce a “turn on” mechanism or alter their 19F signal.


Abstract

Magnetic resonance imaging (MRI) is a powerful and widely used in vivo imaging technique that enables whole body imaging without ionizing radiation. In clinical practice, 1H MRI is employed for imaging anatomical and physiological states via monitoring of protons in water and lipids. In order to monitor biochemical processes at the molecular level, several research groups are exploring responsive MRI agents that alter their signal upon interaction with an analyte or biological environment of interest. Fluorine (19F) MRI agents are promising due to the 19F nucleus having similar magnetic resonance (MR) properties to proton and the absence of endogenous 19F in living systems, resulting in no background signal. In order to make responsive 19F MR agents for molecular imaging and analysis, fluorinated platforms must be developed in which their 19F MR signal changes after interacting with a target analyte. A promising strategy is to use paramagnetic metals to modulate the 19F MR signal by altering the relaxation rates and/or chemical shift of an appended 19F imaging tag. In this concept, we provide an overview of the theoretical principles and molecular design strategies that have been exploited in the design of responsive 19F MR agents, with a specific focus on agents based on small molecule paramagnetic metal ion chelates.

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