Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu Province, People's Republic of China.
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.
Mol Imaging Biol. 2021 Jun;23(3):310-322. doi: 10.1007/s11307-020-01564-y. Epub 2020 Nov 18.
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 [Tc]glucarate and [F]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 [Tc]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 [Tc]glucarate has been found to be closely related to glucose transporter 5 expression. Moreover, the recently developed [F]glucarate provides a new alternative probe for positron emission tomography imaging and may have potential advantages over [Tc]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.
葡萄糖醛酸是哺乳动物 D-葡萄糖醛酸途径的生理终产物，是一种具有广泛用途的六碳二羧酸。以葡萄糖醛酸为基础的分子成像探针，包括 [Tc]葡萄糖醛酸和 [F]葡萄糖醛酸，已经被开发出来并证明具有梗死/坏死亲和性和/或肿瘤靶向性，显示出在早期检测心肌梗死、评估组织活力、监测治疗效果以及对某些肿瘤（包括耐药肿瘤）进行非侵入性成像方面的潜在应用。[Tc]葡萄糖醛酸在急性坏死组织中定位的机制已被证明主要归因于其与带正电荷的组蛋白的结合，这些组蛋白在细胞膜和核膜因不可逆损伤而破裂后变得易于接近，而 [Tc]葡萄糖醛酸的肿瘤靶向机制则与葡萄糖转运蛋白 5 的表达密切相关。此外，最近开发的 [F]葡萄糖醛酸为正电子发射断层扫描成像提供了一种新的替代探针，并且可能比 [Tc]葡萄糖醛酸具有潜在优势。在这篇综述中，我们展示了对以葡萄糖醛酸为基础的分子成像探针作为梗死/坏死亲和剂和/或肿瘤靶向剂的不懈追求。此外，还讨论了葡萄糖醛酸基分子探针的局限性和未来研究的前景。
