A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography

Timothy H. Witney, Laurence Carroll, Israt S. Alam, Anil Chandrashekran, Quang De Nguyen, Roberta Sala, Robert Harris, Ralph J. De Berardinis, Roshan Agarwal, Eric O. Aboagye

Research output: Contribution to journalArticle

Abstract

The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG- PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that 18F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3] triazole-4-yl)glucosamine (18F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating 18F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited 18F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, 18F-NFTG, but not 18F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalCancer Research
Volume74
Issue number5
DOIs
Publication statusPublished - Mar 1 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Witney, T. H., Carroll, L., Alam, I. S., Chandrashekran, A., De Nguyen, Q., Sala, R., ... Aboagye, E. O. (2014). A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography. Cancer Research, 74(5), 1319-1328. https://doi.org/10.1158/0008-5472.CAN-13-2768