Assessing cancer therapeutic efficacy in vivo using [ <sup>2</sup> H <sub>7</sub> ]glucose deuterium metabolic imaging
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-[<sup>18</sup>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-<sup>2</sup>H<sub>2</sub>]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 [<sup>2</sup>H<sub>7</sub>]glucose. Imaging <sup>2</sup>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 <sup>2</sup>H-signal and HDO. To our knowledge this is the first application of DMRI with [<sup>2</sup>H<sub>7</sub>]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.
Authors
- Matthew E. Merritt (ORCID: https://orcid.org/0000-0003-4617-9651)
- Stephen J. Staklinski (ORCID: https://orcid.org/0000-0002-1746-6320)
- Ralph J. DeBerardinis (ORCID: https://orcid.org/0000-0002-2705-7432)
- Brian K. Law (ORCID: https://orcid.org/0000-0002-8411-6531)
- Anna Rushin (ORCID: https://orcid.org/0000-0002-5643-0101)
- Aparna D. Rao (ORCID: https://orcid.org/0000-0002-6394-0011)
- Mario C. Chang (ORCID: https://orcid.org/0000-0002-2452-2693)
- Rohit Mahar (ORCID: https://orcid.org/0000-0002-9801-4173)
- Manoj Madheswaran (ORCID: https://orcid.org/0009-0005-9642-571X)
- James H. P. Collins (ORCID: https://orcid.org/0000-0003-4333-3748)
- Mukundan Ragavan (ORCID: https://orcid.org/0000-0001-8678-4229)
- Geraldine Pierre (ORCID: https://orcid.org/0009-0000-0573-8440)
- James A. Bankson (ORCID: https://orcid.org/0000-0002-8574-154X)
- Vinay Malut (ORCID: https://orcid.org/0009-0005-1006-6323)
- Vikram D. Kodibagkar (ORCID: https://orcid.org/0000-0003-1933-8821)
- Marc McLeod (ORCID: https://orcid.org/0009-0004-5193-3529)
- G. C. Sharma (ORCID: https://orcid.org/0009-0002-3832-0897)
- Arshee Badar
- Max Glanz (ORCID: https://orcid.org/0009-0007-9724-478X)
- Michael S. Kilberg
- Indu R. Malut
Institutions
- Children's Medical Center (US)
- St. Jude Children's Research Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Howard Hughes Medical Institute (US)
- The University of Melbourne (AU)
- Hemwati Nandan Bahuguna Garhwal University (IN)
- Cold Spring Harbor Laboratory (US)
- Peter MacCallum Cancer Centre (AU)
- University of Florida (US)
- Southwestern Medical Center (US)
- National High Magnetic Field Laboratory (US)
- Arizona State University (US)
- The University of Texas Southwestern Medical Center (US)
- Florida College (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1126/sciadv.adr0568
- Citations
- 11
- Primary Topic
- Medical Imaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 14.96