Editorial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Nov 28, 2016; 8(11): 851-856
Published online Nov 28, 2016. doi: 10.4329/wjr.v8.i11.851
Metabolic positron emission tomography imaging of cancer: Pairing lipid metabolism with glycolysis
Sandi A Kwee, John Lim
Sandi A Kwee, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, United States
Sandi A Kwee, John Lim, Hamamatsu/Queen’s PET Imaging Center, the Queen’s Medical Center, Honolulu, HI 96813, United States
Author contributions: Kwee SA and Lim J contributed to conception, data gathering, analysis, writing, and final approval of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sandi A Kwee, MD, PhD, Hamamatsu/Queen’s PET Imaging Center, the Queen’s Medical Center, 1301 Punchbowl St., Honolulu, HI 96813, United States. kwee@hawaii.edu
Telephone: +1-808-6915466 Fax: +1-808-6917813
Received: August 18, 2016
Peer-review started: August 22, 2016
First decision: September 6, 2016
Revised: September 20, 2016
Accepted: October 17, 2016
Article in press: October 18, 2016
Published online: November 28, 2016
Abstract

The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers. However, neither choline nor acetate have been thoroughly validated as lipogenic biomarkers, and while acetyl-CoA produced from acetate is used in de-novo lipogenesis to synthesize fatty acids, acetate is also consumed by various other synthetic and metabolic pathways, with recent experimental observations challenging the assumption that lipogenesis is its predominant role in all cancers. Since tumors detected by acetate PET are also frequently detected by choline PET, imaging of choline metabolism might serve as an alternative albeit indirect marker of lipogenesis, particularly if the fatty acids produced in cancer cells are mainly destined for membrane synthesis through incorporation into phosphatidylcholines. Aerobic glycolysis may or may not coincide with changes in lipid metabolism, resulting in combinatorial metabolic phenotypes that may have different prognostic or therapeutic implications. Consequently, PET imaging using dual metabolic tracers, in addition to being diagnostically superior to imaging with individual tracers, could eventually play a greater role in supporting precision medicine, as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with these metabolic alterations.

Keywords: Glycolysis, Lipogenesis, Fatty acid metabolism, Positron emission tomography, Choline, Acetate, Cancer, Prostate cancer, Hepatocellular carcinoma

Core tip: Positron emission tomography (PET) imaging using multiple distinct metabolic tracers could eventually play a greater role in supporting precision medicine as efforts to develop small-molecule metabolic pathway inhibitors are coming to fruition. To prepare for this advent, clinical and translational studies of metabolic PET tracers must go beyond simply estimating tracer diagnostic utility, and aim to uncover potential therapeutic avenues associated with metabolic alterations in cancer.