Does 2-FDG PET accurately reflect quantitative in vivo glucose utilization?

Jorge R. Barrio, Sung Cheng Huang, Nagichettiar Satyamurthy, Claudio S. Scafoglio, Amy S. Yu, Abass Alavi, Kenneth A. Krohn

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


2-Deoxy-2-18F-fluoro-D-glucose (2-FDG) with PET is undeniably useful in the clinic, being able, among other uses, to monitor change over time using the 2-FDG SUV metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, or LC. This report describes that LC is not constant for a specific tissue and may be variable before and after disease treatment. The purpose of this work is not to deny the clinical value of 2-FDG PET; it is a reminder that when one extends the use of an appropriately qualified imaging method, new observations may arise and further validation would be necessary. The current understanding of glucose-based energetics in vivo is based on the quantification of glucose metabolic rates with 2-FDG PET, a method that permits the noninvasive assessment of various human disorders. However, 2-FDG is a good substrate only for facilitated-glucose transporters (GLUTs), not for sodium-dependent glucose cotransporters (SGLTs), which have recently been shown to be distributed in multiple human tissues. Thus, the GLUT-mediated in vivo glucose utilization measured by 2-FDG PET would be masked to the potentially substantial role of functional SGLTs in glucose transport and use. Therefore, under these circumstances, the 2-FDG LC used to quantify in vivo glucose utilization should not be expected to remain constant. 2-FDG LC variations have been especially significant in tumors, particularly at different stages of cancer development, affecting the accuracy of quantitative glucose measures and potentially limiting the prognostic value of 2-FDG, as well as its accuracy in monitoring treatments. SGLT-mediated glucose transport can be estimated using α-methyl-4-deoxy-4-18F-fluoro-D-glucopyranoside (Me-4FDG). Using both 2-FDG and Me-4FDG should provide a more complete picture of glucose utilization via both GLUT and SGLT transporters in health and disease states. Given the widespread use of 2-FDG PET to infer glucose metabolism, it is relevant to appreciate the potential limitations of 2-FDG as a surrogate for glucose metabolic rate and the potential reasons for variability in LC. Even when the readout for the 2-FDG PET study is only an SUV parameter, variability in LC is important, particularly if it changes over the course of disease progression (e.g., an evolving tumor).

Original languageEnglish (US)
Pages (from-to)931-937
Number of pages7
JournalJournal of Nuclear Medicine
Issue number6
StatePublished - Jun 1 2020


  • Lumped constant
  • SGLTs

ASJC Scopus subject areas

  • Medicine(all)


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