Chang Mario C, Malut Vinay R, Mahar Rohit, Rushin Anna, McLeod Marc A, Pierre Geraldine L, Malut Indu R, Staklinski Stephen J, Glanz Max E, Ragavan Mukundan, Sharma Gaurav, Madheswaran Manoj, Badar Arshee, Rao Aparna D, Law Brian K, Kilberg Michael S, Collins James H P, Kodibagkar Vikram D, Bankson James A, DeBerardinis Ralph J, Merritt Matthew E
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Department of Chemistry, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar Garhwal, Uttarakhand 246174, India.
Sci Adv. 2025 Mar 28;11(13):eadr0568. doi: 10.1126/sciadv.adr0568. Epub 2025 Mar 26.
Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-H]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [H]glucose. Imaging H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or anti-glycolytic BRAFi and MEKi therapy, and contralateral healthy tissue. Control tumors generated the most H-signal and HDO. To our knowledge this is the first application of DMRI with [H]glucose for tumoral treatment monitoring. This approach demonstrates HDO as a marker of tumor glucose utilization and suggests translational capability in humans due to its safety, noninvasiveness, and suitability for serial monitoring.
代谢成像可在体内对器官功能进行强有力的可视化评估。通过安全地增加代谢对比度,当前技术可得到改进。金标准——2-[F]氟脱氧葡萄糖正电子发射断层扫描(FDG-PET)成像,受放射性暴露以及对葡萄糖摄取和潴留以外的代谢评估不足的限制。使用[6,6-H]葡萄糖的氘磁共振成像(DMRI)无放射性,可实现肿瘤代谢对比度,但基于氘代水(HDO)的成像所产生的富集对比度可对其加以改进。在此,我们开发了一种采用[H]葡萄糖的DMRI方案。对荷瘤小鼠的H信号进行成像并测量HDO生成情况,可检测出基线肿瘤、接受载体对照或抗糖酵解BRAFi和MEKi治疗的肿瘤以及对侧健康组织之间不同的葡萄糖利用情况。对照肿瘤产生的H信号和HDO最多。据我们所知,这是首次将采用[H]葡萄糖的DMRI应用于肿瘤治疗监测。这种方法证明HDO可作为肿瘤葡萄糖利用的标志物,并因其安全性、非侵入性以及适用于连续监测而表明具有在人体中的转化能力。