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PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2

Witney, TH; James, ML; Shen, B; Chang, E; Pohling, C; Arksey, N; Hoehne, A; ... Gambhir, SS; + view all (2015) PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2. Science Translational Medicine , 7 (310) , Article 310ra169. 10.1126/scitranslmed.aac6117. Green open access

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Abstract

Cancer cells reprogram their metabolism to meet increased biosynthetic demands, commensurate with elevated rates of replication. Pyruvate kinase M2 (PKM2) catalyzes the final and rate-limiting step in tumor glycolysis, controlling the balance between energy production and the synthesis of metabolic precursors. We report here the synthesis and evaluation of a positron emission tomography (PET) radiotracer, [(11)C]DASA-23, that provides a direct noninvasive measure of PKM2 expression in preclinical models of glioblastoma multiforme (GBM). In vivo, orthotopic U87 and GBM39 patient-derived tumors were clearly delineated from the surrounding normal brain tissue by PET imaging, corresponding to exclusive tumor-associated PKM2 expression. In addition, systemic treatment of mice with the PKM2 activator TEPP-46 resulted in complete abrogation of the PET signal in intracranial GBM39 tumors. Together, these data provide the basis for the clinical evaluation of imaging agents that target this important gatekeeper of tumor glycolysis.

Type: Article
Title: PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scitranslmed.aac6117
Publisher version: http://dx.doi.org/10.1126/scitranslmed.aac6117
Language: English
Additional information: Copyright © 2015, American Association for the Advancement of Science. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine, vol. 7, on 21/10/15, DOI: 10.1126/scitranslmed.aac6117.
UCL classification: UCL
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 > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1472072
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