Untiring Pursuit for Glucarate-Based Molecular Imaging Probes

Glucarate, a physiologic end-product of the D-glucuronic acid pathway in mammals, is a six-carbon dicarboxylic acid with a wide range of uses. Glucarate-based molecular imaging probes including [99mTc]glucarate and [18F]glucarate have been developed and demonstrated to have infarct/necrosis-avid and/or tumor-seeking properties, showing potential applications in early detection of myocardial infarction, evaluation of tissue viability, monitoring of therapeutic effectiveness, and noninvasive imaging of certain tumors including drug-resistant ones. The mechanism by which [99mTc]glucarate localizes in acute necrotic tissues has been demonstrated to be largely attributable to its binding to the positively charged histones, which become accessible after the disruption of the cell and nuclear membranes as a result of irreversible damage, while the tumor-seeking mechanism of [99mTc]glucarate has been found to be closely related to glucose transporter 5 expression. Moreover, the recently developed [18F]glucarate provides a new alternative probe for positron emission tomography imaging and may have potential advantages over [99mTc]glucarate. In this review, we present the untiring pursuit for glucarate-based molecular imaging probes as infarct/necrosis-avid agent and/or tumor-seeking agent. Moreover, the limitations and the prospects for future research of glucarate-based molecular probes are also discussed.