Untiring Pursuit for Glucarate-Based Molecular Imaging Probes
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REVIEW ARTICLE
Untiring Pursuit for Glucarate-Based Molecular Imaging Probes Dongjian Zhang,1,2 Qiaomei Jin,1,2 Meng Gao,1,2 Cuihua Jiang,1,2 Yicheng Ni,3 Jian Zhang 1,2 1
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu Province, People’s Republic of China 2 Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, No.100, Shizi Street, Hongshan Road, Nanjing, 210028, Jiangsu Province, People’s Republic of China 3 Theragnostic Laboratory, Campus Gasthuisberg, KU Leuven, 3000, Leuven, Belgium
Abstract Glucarate, a physiologic end-product of the D-glucuronic acid pathway in mammals, is a sixcarbon 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. Key words: [99mTc]glucarate, [18F]glucarate, Necrosis-avid property, Tumor-seeking property, Molecular imaging, Histones, GLUT-5
Introduction Glucarate (Fig. 1), a physiologic end-product of the Dglucuronic acid pathway in mammals, is a six-carbon dicarboxylic acid that has been widely used in food, pharmaceutical, and chemical industries [1–4]. Initially, it was used as a transchelator of Tc-99m for radiolabeling
Dongjian Zhang and Qiaomei Jin contributed equally to this work. Correspondence to: Jian Zhang; e-mail: [email protected]
antibody fragments [5–7]. Accidentally, it was found that when Tc-99m-labeled glucarate ([99mTc]glucarate, Fig. 1) was intravenously injected alone, it could specifically localize in zones of cerebral and myocardial injuries shortly after acute infarction in animals [8–12]. Further studies demonstrated that [99mTc]glucarate could be used for very early noninvasive detection of both reperfused and persistently occluded acute experimental myocardial infarc
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