Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

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Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. / Busk, Morten; Horsman, Michael R; Jakobsen, Steen; Bussink, Johan; van der Kogel, Albert; Overgaard, Jens.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 35, No. 12, 12.2008, p. 2294-303.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Busk, M, Horsman, MR, Jakobsen, S, Bussink, J, van der Kogel, A & Overgaard, J 2008, 'Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage', European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 12, pp. 2294-303. https://doi.org/10.1007/s00259-008-0888-9

APA

Busk, M., Horsman, M. R., Jakobsen, S., Bussink, J., van der Kogel, A., & Overgaard, J. (2008). Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. European Journal of Nuclear Medicine and Molecular Imaging, 35(12), 2294-303. https://doi.org/10.1007/s00259-008-0888-9

CBE

Busk M, Horsman MR, Jakobsen S, Bussink J, van der Kogel A, Overgaard J. 2008. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. European Journal of Nuclear Medicine and Molecular Imaging. 35(12):2294-303. https://doi.org/10.1007/s00259-008-0888-9

MLA

Busk, Morten et al. "Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage". European Journal of Nuclear Medicine and Molecular Imaging. 2008, 35(12). 2294-303. https://doi.org/10.1007/s00259-008-0888-9

Vancouver

Busk M, Horsman MR, Jakobsen S, Bussink J, van der Kogel A, Overgaard J. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. European Journal of Nuclear Medicine and Molecular Imaging. 2008 Dec;35(12):2294-303. https://doi.org/10.1007/s00259-008-0888-9

Author

Busk, Morten ; Horsman, Michael R ; Jakobsen, Steen ; Bussink, Johan ; van der Kogel, Albert ; Overgaard, Jens. / Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. In: European Journal of Nuclear Medicine and Molecular Imaging. 2008 ; Vol. 35, No. 12. pp. 2294-303.

Bibtex

@article{450e5e40f6a111dd8f9a000ea68e967b,
title = "Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage",
abstract = "PURPOSE: Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines. METHODS: Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. RESULTS: Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG. CONCLUSIONS: [(18)F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.",
author = "Morten Busk and Horsman, {Michael R} and Steen Jakobsen and Johan Bussink and {van der Kogel}, Albert and Jens Overgaard",
year = "2008",
month = "12",
doi = "10.1007/s00259-008-0888-9",
language = "English",
volume = "35",
pages = "2294--303",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage

AU - Busk, Morten

AU - Horsman, Michael R

AU - Jakobsen, Steen

AU - Bussink, Johan

AU - van der Kogel, Albert

AU - Overgaard, Jens

PY - 2008/12

Y1 - 2008/12

N2 - PURPOSE: Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines. METHODS: Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. RESULTS: Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG. CONCLUSIONS: [(18)F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.

AB - PURPOSE: Tumour hypoxia and elevated glycolysis (Warburg effect) predict poor prognosis. Each parameter is assessable separately with positron emission tomography, but they are linked through anaerobic glycolysis (Pasteur effect). Here, we compare the oxygenation-dependent retention of fluoroazomycin arabinoside ([(18)F]FAZA), a promising but not well-characterised hypoxia-specific tracer, and fluorodeoxyglucose ([(18)F]FDG) in four carcinoma cell lines. METHODS: Cells seeded on coverslips were positioned in modified Petri dishes that allow physically separated cells to share the same tracer-containing medium pool. Following oxic, hypoxic or anoxic tracer incubation, coverslips were analysed for radioactivity ([(18)F]FDG + [(18)F]FAZA) or re-incubated in tracer-free oxygenated medium and then measured ([(18)F]FAZA). Next, we tested the reliability of [(18)F]FDG as a relative measure of glucose metabolic rate. Finally, from two cell lines, xenografts were established in mice, and the tracer distribution between hypoxic and well-oxygenated areas were deduced from tissue sections. RESULTS: Three hours of anoxia strongly stimulated [(18)F]FAZA retention with anoxic-to-oxic uptake ratios typically above 30. Three out of four cell lines displayed similar selectivity of [(18)F]FDG versus glucose, but oxic uptake and anoxic-to-oxic uptake ratio of [(18)F]FDG varied considerably. Although less pronounced, [(18)F]FAZA also showed superior in vivo hypoxia specificity compared with [(18)F]FDG. CONCLUSIONS: [(18)F]FAZA displays excellent in vitro characteristics for hypoxia imaging including modest cell-to-cell line variability and no binding in oxic cells. In contrast, the usability of [(18)F]FDG as a surrogate marker for hypoxia is questionable due to large variations in baseline (oxic) glucose metabolism and magnitudes of the Pasteur effects.

U2 - 10.1007/s00259-008-0888-9

DO - 10.1007/s00259-008-0888-9

M3 - Journal article

C2 - 18682937

VL - 35

SP - 2294

EP - 2303

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 12

ER -