Witney, TH; James, ML; Shen, B; Chang, E; Pohling, C; Arksey, N; Hoehne, A; ... Gambhir, SS; + view all Witney, TH; James, ML; Shen, B; Chang, E; Pohling, C; Arksey, N; Hoehne, A; Shuhendler, A; Park, JH; Bodapati, D; Weber, J; Gowrishankar, G; Rao, J; Chin, FT; Gambhir, SS; - view fewer (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.

Preview	Text Witney_aac6117_final edits.pdf Download (1MB) | Preview
Preview	Text Witney_aac6117_SupplementalMaterial_final edits.pdf Download (741kB) | Preview

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.

Download activity - last month

Export as JSONCSVXML

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item