Assessing cancer therapeutic efficacy in vivo using [ <sup>2</sup> H <sub>7</sub> ]glucose deuterium metabolic imaging
Mario C. Chang, Vinay Malut, Rohit Mahar, Anna Rushin, Marc McLeod, Geraldine Pierre, Indu R. Malut, Stephen J. Staklinski, Max Glanz, Mukundan Ragavan, G. C. Sharma, Manoj Madheswaran, Arshee Badar, Aparna D. Rao, Brian K. Law, Michael S. Kilberg, James H. P. Collins, Vikram D. Kodibagkar, James A. Bankson, Ralph J. DeBerardinis, Matthew E. Merritt
Abstract
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-[ 18 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- 2 H 2 ]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 [ 2 H 7 ]glucose. Imaging 2 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 2 H-signal and HDO. To our knowledge this is the first application of DMRI with [ 2 H 7 ]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.