Abstract SY02-03: Imaging cancer metabolism in patients: FDG PET and beyond
Authors: David A. Mankoff
Journal: Cancer Research (2017)

Abstract The identification of altered energy metabolism as a hallmark of cancer (1) leads to opportunities to exploit cancer metabolism as a target for diagnosis. This has been most widely exploited using the elevated rate of glycolysis observed in most tumors as a target for imaging (2)–in particular, positron emission tomography (PET) imaging of the glucose analog 18F-fluorodeoxyglucose (FDG). FDG PET, now combined with anatomic imaging in the form of PET/CT, has become an important tool for cancer detection, staging, and response assessment, widely used in oncologic clinical practices around the world (3,4). Clinical use of FDG PET has increased our appreciation of aberrant glycolysis as a feature of more aggressive, less differentiated tumors (5,6). At the same time, the variability of tumor FDG uptake seen in clinical imaging has highlighted some of the limitations of imaging tumor glycolysis and has spurred the development of new imaging probes and novel imaging modalities designed to image other facets of cancer energy metabolism. In addition, the use of therapeutics that are targeted to and/or influenced by cancer metabolic phenotype (7) drives applications of cancer metabolic imaging to clinical challenges beyond detection to predicting and and monitoring response to targeted therapy (8). This talk highlights current uses of FDG PET/CT for cancer staging and response evaluation, as well as alternative PET probes targeted to other metabolic substrates such as amino acids, lipids, and TCA intermediates (9). It also highlights other methods for imaging cancer metabolism in patients, including magnetic resonance spectroscopy, optical imaging, chemical exchange saturation transfer (CEST), MR metabolomics, and MR imaging of hyperpolarized 13C-labeled metabolic substrates such as pyruvate (10-14). Unique features and advantages of each modality are highlighted, as are approaches to image analysis common across modalities, including quantitative imaging and kinetic analysis. Finally, the talk emphasizes the benefit of multimodality imaging as an approach to fully characterize cancer metabolism, using glutaminolysis imaging as an example of active investigation. Supported in part by Komen SAC130060, DOE DE-SE0012476, NIH P30-CA016520, and NIH R01-CA211337. References 1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74. 2. Gillies RJ, Gatenby RA. Metabolism and its sequelae in cancer evolution and therapy. Cancer J 2015;21:88-96. 3. Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005;11:2785-808. 4. Mankoff DA, Eary JF, Link JM, Muzi M, Rajendran JG, Spence AM, et al. Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin Cancer Res 2007;13:3460-9. 5. Alvarez JV, Belka GK, Pan TC, Chen CC, Blankemeyer E, Alavi A, et al. Oncogene pathway activation in mammary tumors dictates FDG-PET uptake. Cancer Res 2014;74:7583-98. 6. Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D, et al. 18F-Fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers. Cancer Res 2011;71:5164-74. 7. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 2007;104:19345-50. 8. Mankoff DA, Farwell MD, Clark AS, Pryma DA. Making molecular imaging a clinical tool for precision oncology: a review. JAMA Oncol 2016 Dec 29. [Epub ahead of print] 9. Lewis DY, Soloviev D, Brindle KM. Imaging tumor metabolism using positron emission tomography. Cancer J 2015;21:129-36. 10. Griffiths JR, Glickson JD. Monitoring pharmacokinetics of anticancer drugs: non-invasive investigation using magnetic resonance spectroscopy. Adv Drug Deliv Rev 2000;41:75-89. 11. Kogan F, Hariharan H, Reddy R. Chemical exchange saturation transfer (CEST) imaging: description of technique and potential clinical applications. Curr Radiol Rep 2013;1:102-14. 12. Mahmood U. Near infrared optical applications in molecular imaging. Earlier, more accurate assessment of disease presence, disease course, and efficacy of disease treatment. IEEE Eng Med Biol Mag 2004;23:58-66. 13. Weissleder R, Schwaiger MC, Gambhir SS, Hricak H. Imaging approaches to optimize molecular therapies. Sci Transl Med 2016;8:355ps16. 14. Wilson DM, Kurhanewicz J. Hyperpolarized 13C MR for molecular imaging of prostate cancer. J Nucl Med 2014;55:1567-72. Citation Format: David A. Mankoff. Imaging cancer metabolism in patients: FDG PET and beyond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY02-03. doi:10.1158/1538-7445.AM2017-SY02-03