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Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts

Dearling, JLJ; Flynn, AA; Sutcliffe-Goulden, J; Petrie, IA; Boden, R; Green, AJ; Boxer, GM; ... Pedley, RB; + view all (2004) Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. J NUCL MED , 45 (1) 101 - 107.

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Abstract

It has been shown in vitro that the cell uptake of F-18-FDG, a tracer of glucose metabolism, increases under hypoxia. This is consistent with increased glycolytic metabolism. We have previously shown that in ischemic heart ex vivo the rates of uptake of F-18-FDG and 2-C-14-deoxy-D-glucose (C-14-2DG) are both reduced. In this study, we investigated this effect in tumors by comparing the microdistribution of F-18-FDG and C-14-2DG in hypoxic and normoxic regions. Methods: Mice (MF1) bearing LS174T human tumor xenografts were injected with premixed 18F-FDG (100 MBq), C-14-2DG (0.37 MBq), and pimoniclazole hydrochloride (60 mg/kg). After 30, 60, and 120 min, tissues (n = 4) were taken and counted for whole-body biodistribution. Tumors were frozen, sectioned, and exposed to phosphor image plates to obtain a quantitative digital image of radionuclide distribution. Sections were then stained to reveal tumor pathophysiology: Hematoxylin and eosin staining demonstrated viable and necrotic regions, and immunohistochemical staining detected pimoniclazole metabolism in hypoxic cells. The images of radionuclide microdistribution and histology were then coregistered and analyzed to assess radionuclide trapping throughout the tumor on a pixel-by-pixel basis. The Pearson correlation coefficients between the 2 radionuclides were calculated. The relative amounts of nuclide were then analyzed in viable and necrotic regions and in normoxic and hypoxic regions. Results: Whole-body biodistributions for the 2 radiotracers were similar. A high Pearson correlation coefficient was obtained for the 2 radionuclides throughout the tumors (r = 0.85 +/- 0.10, P < 0.0001), indicating a highly similar microdistribution. When the tumors were divided into viable and necrotic regions, the ratio of mean counts per pixel was 1.96 (P < 0.0001), whereas for hypoxic versus normoxic regions it was 1.26 (P < 0.0001). There was no significant difference in selectivity for hypoxia between the 2 radiotracers (P = 0.86). Conclusion: The tumor microdistribution of deoxyglucose in viable, hypoxic, and necrotic regions show that there was little change in the microdistribution of deoxyglucose throughout this time course. This study extends previous in vitro work and confirms the selectivity of deoxyglucose for viable cells over necrotic regions and for hypoxic cells over normoxic regions in vivo.

Type: Article
Title: Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts
Keywords: F-18-FDG, 2-C-14-deoxy-D-glucose, tumor metabolism, CEREBRAL GLUCOSE-UTILIZATION, CANCER-CELLS, F-18 2-DEOXY-2-FLUORO-D-GLUCOSE, FLUORODEOXYGLUCOSE UPTAKE, RAT-HEART, HYPOXIA, BIODISTRIBUTION, METABOLISM, FDG
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/158317
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