Hyperpolarized MRI Enhances Early Detection Treatment-induced Changes in Glycolysis.

Abstract

HomeRadiology: Imaging CancerVol. 1, No. 1 PreviousNext Research HighlightsFree AccessHyperpolarized MRI Enhances Early Detection Treatment-induced Changes in GlycolysisAlyssa C. Cutter, Gary D. LukerAlyssa C. Cutter, Gary D. LukerAlyssa C. CutterGary D. LukerPublished Online:Sep 27 2019https://doi.org/10.1148/rycan.2019194001MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major focus: Comparing hyperpolarized [1-carbon 13 (13C)] pyruvate MRI spectroscopy with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET as metabolic imaging methods to detect early effects of treatment in mouse models of cancer.■ Key result: Treatment-induced death of cancer cells decreased glycolysis by 24 hours as measured by hyperpolarized [1-13C] pyruvate MRI but not 18F FDG PET.■ Impact: As compared with 18F FDG PET, hyperpolarized MRI [1-13C] pyruvate imaging of glycolysis improves early detection of cancer cell death.Changes in tumor size remain the standard metric for assessing response to cancer therapy, but such changes occur slowly and may fail to capture effects of molecularly targeted drugs. Since malignant cells commonly increase glycolytic metabolism, imaging reductions in glycolysis can shorten the timescale between starting therapy and determining success or failure of treatment. Fluorine 18 (18F) fluorodeoxyglucose (FDG) PET, which quantifies intracellular transport and phosphorylation of the glucose analog 18F FDG, is the standard imaging method for cancer metabolism. However, treatment frequently causes a paradoxical early increase in signal, the “flare effect”, which delays reliable measurements of response to treatment. Hyperpolarization markedly increases signal from molecules labeled with carbon 13 (13C), enabling MRI measurements of glycolytic flux based on metabolism of injected [1-13C] pyruvate to [1-13C]-lactate. Hesketh and colleagues compared these alternative imaging methods as markers of early response to therapy in xenograft models of cancer in immunocompromised mice. Treatment with a compound that selectively induced death in cancer cells decreased biochemical measures of glycolysis in tumors by 24 hours. Imaging with hyperpolarized [1-13C] pyruvate MRI, but not 18F FDG PET, consistently detected treatment-induced reductions in tumor glycolysis. Infiltration of treated tumors by highly glycolytic macrophages has been proposed to cause the flare effect in early 18F FDG PET studies. Hesketh and colleagues found few macrophages in treated tumors, excluding uptake of 18F FDG by these immune cells as the cause of no change in overall radiotracer uptake. While limited by use of immunocompromised mice and subcutaneous cell line xenografts, this study suggests hyperpolarized [1-13C] pyruvate MRI improves early treatment monitoring in cancer with the potential to better inform precision therapy.Highlighted ArticleHesketh RL, Wang J, Wright AJ et al. Magnetic resonance imaging is more sensitive than PET for detecting treatment-induced cell death-dependent changes in glycolysis. Cancer Res 2019; 79 (14): 3557-3569. doi: 10.1158/0008-5472.CAN-19-0182.Highlighted Article Hesketh RL, Wang J, Wright AJ, et al. Magnetic resonance imaging is more sensitive than PET for detecting treatment-induced cell death-dependent changes in glycolysis . Cancer Res 2019; 79(14):3557-3569. doi: 10.1158/0008-5472.CAN-19-0182. Crossref, Medline, Google ScholarArticle HistoryPublished online: Sept 27 2019 FiguresReferencesRelatedDetailsRecommended Articles In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse ModelRadiology2017Volume: 285Issue: 3pp. 830-838Hyperpolarized Pyruvate MR Spectroscopy Depicts Glycolytic Inhibition in a Mouse Model of GliomaRadiology2019Volume: 293Issue: 1pp. 168-173Assessing Oximetry Response to Chimeric Antigen Receptor T-cell Therapy against Glioma with 19F MRI in a Murine ModelRadiology: Imaging Cancer2021Volume: 3Issue: 1Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to MetabolismRadioGraphics2020Volume: 41Issue: 1pp. 120-143Imaging Telomerase as a Marker of Response to TherapyRadiology: Imaging Cancer2022Volume: 4Issue: 5See More RSNA Education Exhibits Assessing Immunotherapy with Functional and Molecular Imaging and Radiomics: Whence and WitherDigital Posters2019Imaging Biomarkers in Targeted Therapies: From Quantitative Imaging to RadiomicsDigital Posters2019Imaging Challenges for Evaluation of Treated Glioblastoma: Past, Present and FutureDigital Posters2019 RSNA Case Collection Pseudoprogression with Immunotherapy Treatment RSNA Case Collection2021Malignant Cardiac PEComaRSNA Case Collection2021Solitary intracranial metastasis RSNA Case Collection2020 Vol. 1, No. 1 Metrics Altmetric Score PDF download