PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2.
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.
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Timothy H
TH
Witney
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA. Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 943065, USA.
Michelle L
ML
James
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Bin
B
Shen
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Edwin
E
Chang
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Christoph
C
Pohling
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Natasha
N
Arksey
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Aileen
A
Hoehne
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Adam
A
Shuhendler
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Jun-Hyung
JH
Park
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Deepika
D
Bodapati
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Judith
J
Weber
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Gayatri
G
Gowrishankar
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Jianghong
J
Rao
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA.
Frederick T
FT
Chin
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 943065, USA. Departments of Bioengineering and Materials Science & Engineering, Bio-X, Stanford University, Stanford, CA 943065, USA. sgambhir@stanford.edu.
Sanjiv Sam
SS
Gambhir
D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology; D002250:Carbon Radioisotopes; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D049268:Positron-Emission Tomography; D011770:Pyruvate Kinase / Q000378:metabolism*
D002250:Carbon Radioisotopes; D006593:Hexokinase; D011770:Pyruvate Kinase