Witney T.H.,Comprehensive Cancer Imaging Center |
Carroll L.,Comprehensive Cancer Imaging Center |
Alam I.S.,Comprehensive Cancer Imaging Center |
Chandrashekran A.,Comprehensive Cancer Imaging Center |
And 6 more authors.
Cancer Research | Year: 2014
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. © 2013 American Association for Cancer Research.
Fruhwirth G.O.,King's College London |
Fruhwirth G.O.,Comprehensive Cancer Imaging Center |
Fernandes L.P.,King's College London |
Weitsman G.,King's College London |
And 16 more authors.
ChemPhysChem | Year: 2011
Herein we discuss how FRET imaging can contribute at various stages to delineate the function of the proteome. Therefore, we briefly describe FRET imaging techniques, the selection of suitable FRET pairs and potential caveats. Furthermore, we discuss state-of-the-art FRET-based screening approaches (underpinned by protein interaction network analysis using computational biology) and preclinical intravital FRET-imaging techniques that can be used for functional validation of candidate hits (nodes and edges) from the network screen, as well as measurement of the efficacy of perturbing these nodes/edges by short hairpin RNA (shRNA) and/or small molecule-based approaches. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA.