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

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 (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-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 (18)F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating (18)F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited (18)F-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, (18)F-NFTG, but not (18)F-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.

DOI: 10.1158/0008-5472.CAN-13-2768
01002003002014201520162017
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@article{Witney2014ANR, title={A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography.}, author={Timothy Howard Witney and Laurence S. Carroll and Israt S. Alam and Anil Chandrashekran and Quang-de Nguyen and Roberta Sala and Robert J. Harris and Ralph J DeBerardinis and Roshan Agarwal and Eric O. Aboagye}, journal={Cancer research}, year={2014}, volume={74 5}, pages={1319-28} }