Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Mar 28, 2015; 7(3): 57-60
Published online Mar 28, 2015. doi: 10.4329/wjr.v7.i3.57
Metformin and cancer: Technical and clinical implications for FDG-PET imaging
Selene Capitanio, Cecilia Marini, Gianmario Sambuceti, Silvia Morbelli
Selene Capitanio, Gianmario Sambuceti, Silvia Morbelli, Nuclear Medicine Unit, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Cecilia Marini, CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa, 16132 Genoa, Italy
Author contributions: Morbelli S designed the study; Capitanio S performed literature search and draft the manuscript; Marini C, Sambuceti G and Morbelli S made critical revisions related to important intellectual content of the manuscript; Morbelli S have given final approval of the version of the article to be published; all authors read and approved the final manuscript.
Conflict-of-interest: The authors have no conflict of interest to declare.
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: Silvia Morbelli, Full Staff, Nuclear Medicine Unit, IRCCS AOU San Martino-IST, Department of Health Sciences, University of Genoa, L.go R. Benzi, 10, 16132 Genova, Italy. silviadaniela.morbelli@hsanmartino.it
Telephone: +39-10-5552025 Fax: +39-10-5556911
Received: November 7, 2014
Peer-review started: November 9, 2014
First decision: December 12, 2014
Revised: January 15, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: March 28, 2015
Abstract

Metformin is the most widely used hypoglycemic agent. Besides its conventional indications, increasing evidence demonstrate a potential efficacy of this biguanide as an anticancer drug. Possible mechanisms of actions seem to be independent from its hypoglycemic effect and seem to involve the interference with key pathways in cellular proliferation and glycolysis. To date, many clinical trials implying the use of metformin in cancer treatment are on-going. The increasing use of 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in cancer evaluation raises a number of questions about the possible interference of the biguanide on FDG distribution. In particular, the interferences exerted by metformin on AMP-activated protein kinase pathway (the cellular energy sensor), on insulin levels and on Hexokinase could potentially have repercussion on glucose handling and thus on FDG distribution. A better comprehension of the impact of metformin on FDG uptake is needed in order to optimize the use of PET in this setting. This evaluation would be useful to ameliorate scans interpretation in diabetic patients under chronic metformin treatment and to critically interpret images in the context of clinical trials. Furthermore, collecting prospective data in this setting would help to verify whether FDG-PET could be a valid tool to appreciate the anticancer effect of this new therapeutic approach.

Keywords: Metformin, Cancer, 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography, Diabetes, Glucose metabolism

Core tip: Given the recent increasing number of clinical trials involving the use of metformin as anticancer agent and with the widespread use of 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), this editorial deals with a critical evaluation of the main variables regulating FDG uptake that could be potentially influenced by the biguanide. This analysis could optimize not only the interpretation of PET images in diabetic patients but could also help to verify whether FDG-PET could be a valid tool to appreciate anticancer potential of this new therapeutic approach thus opening a new window on clinical trials.