LAUSR

Molecular imaging is a tool that can visualize and quantify biological processes at the molecular and cellular levels in living systems1, and it is therefore ideally suited to the study of cancer metabolism in patients2. In the clinic, molecular imaging of cancer metabolism has been most widely exploited using the elevated rate of glycolysis observed in most tumors as a target for cancer detection and staging using positron emission tomography (PET) and the glucose analog 18F-fluordeoxyglucose (FDG)3. 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. Clinical use of FDG PET has increased our appreciation of aberrant glycolysis as a feature of more aggressive, less differentiated tumors4. 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 phenotype5 drive applications of cancer metabolic imaging to clinical challenges beyond detection that include predicting and monitoring response to targeted therapy6. This talk will briefly review the underpinnings of the current use of FDG PET/CT for cancer staging and response evaluation. The talk will beyond FDG PET and discuss alternative PET probes targeted to other metabolic substrates such as amino acids, lipids, and TCA intermediates7, as well as new instrumentation that offers unique capabilities for imaging whole-body cancer metabolism imaging8. The talk will also highlight other methods for imaging cancer metabolism in patients, especially hyperpolarized 13C-labeled metabolic substrates such as pyruvate9. Unique features and advantages of each modality will be highlighted, as will approaches to image analysis common across modalities, including quantitative imaging and kinetic analysis. Finally, the talk will emphasize benefit of multi-modality imaging as an approach to fully characterize cancer metabolism, using glutaminolysis imaging as an example of active investigation. Supported in part by Komen SAC130060, NIH P30-CA016520, and NIH R01-CA211337. References 1. Mankoff DA: A definition of molecular imaging. J Nucl Med 48:18N, 21N, 2007 2. Jaffee EM, Dang CV, Agus DB, et al: Future cancer research priorities in the USA: a Lancet Oncology Commission. Lancet Oncol 18:e653-e706, 2017 3. Kelloff GJ, Hoffman JM, Johnson B, et al: Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 11:2785-808, 2005 4. Alvarez JV, Belka GK, Pan TC, et al: Oncogene pathway activation in mammary tumors dictates FDG-PET uptake. Cancer Res 74:7583-98, 2014 5. DeBerardinis RJ, Mancuso A, Daikhin E, 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 U S A 104:19345-50, 2007 6. Mankoff DA, Farwell MD, Clark AS, et al: Making Molecular Imaging a Clinical Tool for Precision Oncology: A Review. JAMA Oncol, 2016 7. Pantel AR, Ackerman D, Lee SC, et al: Imaging Cancer Metabolism: Underlying Biology and Emerging Strategies. J Nucl Med 59:1340-1349, 2018 8. Cherry SR, Badawi RD, Karp JS, et al: Total-body imaging: Transforming the role of positron emission tomography. Sci Transl Med 9, 2017 9. Kurhanewicz J, Vigneron DB, Ardenkjaer-Larsen JH, et al: Hyperpolarized (13)C MRI: Path to Clinical Translation in Oncology. Neoplasia 21:1-16, 2019 Citation Format: David Mankoff, Austin Pantel, Rong Zhou, Terenc Gade. Imaging cancer metabolism in patients: Beyond FDG PET [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA24.