title: Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.
abstract: Glucose and glutamine are the two principal nutrients that cancer cells use to proliferate and survive. Many cancers show altered glucose metabolism, which constitutes the basis for in vivo positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)F-FDG). However, (18)F-FDG is ineffective in evaluating gliomas because of high background uptake in the brain. Glutamine metabolism is also altered in many cancers, and we demonstrate that PET imaging in vivo with the glutamine analog 4-(18)F-(2S,4R)-fluoroglutamine ((18)F-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced (18)F-FGln tumor avidity, corresponding with decreased tumor burden. (18)F-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where (18)F-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that (18)F-FGln is avidly taken up by gliomas, can be used to assess metabolic nutrient uptake in gliomas in vivo, and may serve as a valuable tool in the clinical management of gliomas.
authors: Department of Pathology, University of Michigan, Ann Arbor, MI 41809, USA. svenneti@med.umich.edu thompsonc@mskcc.org lewisj2@mskcc.org.
authors: Sriram
authors: S
authors: Venneti
authors: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
authors: Mark P
authors: MP
authors: Dunphy
authors: Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY 10065, USA.
authors: Hanwen
authors: H
authors: Zhang
authors: Cancer Biology and Genetics Program, MSKCC, New York, NY 10065, USA.
authors: Kenneth L
authors: KL
authors: Pitter
authors: Medical Physics, MSKCC, New York, NY 10065, USA.
authors: Patrick
authors: P
authors: Zanzonico
authors: Human Oncology and Pathogenesis Program, MSKCC, New York, NY 10065, USA.
authors: Carl
authors: C
authors: Campos
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, MSKCC, New York, NY 10065, USA.
authors: Sean D
authors: SD
authors: Carlin
authors: Cancer Biology and Genetics Program, MSKCC, New York, NY 10065, USA.
authors: Gaspare
authors: G
authors: La Rocca
authors: Radiochemistry and Molecular Imaging Probe Core, MSKCC, New York, NY 10065, USA.
authors: Serge
authors: S
authors: Lyashchenko
authors: Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Karl
authors: K
authors: Ploessl
authors: Cancer Biology and Genetics Program, MSKCC, New York, NY 10065, USA. Human Oncology and Pathogenesis Program, MSKCC, New York, NY 10065, USA.
authors: Daniel
authors: D
authors: Rohle
authors: Department of Neurology, MSKCC, New York, NY 10065, USA.
authors: Antonio M
authors: AM
authors: Omuro
authors: Donald B. and Catherine C. Marron Cancer Metabolism Center, MSKCC, New York, NY 10065, USA.
authors: Justin R
authors: JR
authors: Cross
authors: Medical Physics, MSKCC, New York, NY 10065, USA. Department of Neurosurgery, MSKCC, New York, NY 10065, USA.
authors: Cameron W
authors: CW
authors: Brennan
authors: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA. Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY 10065, USA.
authors: Wolfgang A
authors: WA
authors: Weber
authors: Director, Solid Tumor Translational Research, Division of Human Biology, Fred Hutchinson Cancer Research Center, and Alvord Brain Tumor Center, University of Washington, Seattle, WA 98109, USA.
authors: Eric C
authors: EC
authors: Holland
authors: Human Oncology and Pathogenesis Program, MSKCC, New York, NY 10065, USA. Department of Neurology, MSKCC, New York, NY 10065, USA.
authors: Ingo K
authors: IK
authors: Mellinghoff
authors: Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Hank F
authors: HF
authors: Kung
authors: Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY 10065, USA. Radiochemistry and Imaging Sciences Service, Department of Radiology, MSKCC, New York, NY 10065, USA. Radiochemistry and Molecular Imaging Probe Core, MSKCC, New York, NY 10065, USA. svenneti@med.umich.edu thompsonc@mskcc.org lewisj2@mskcc.org.
authors: Jason S
authors: JS
authors: Lewis
authors: Cancer Biology and Genetics Program, MSKCC, New York, NY 10065, USA. Human Oncology and Pathogenesis Program, MSKCC, New York, NY 10065, USA. svenneti@med.umich.edu thompsonc@mskcc.org lewisj2@mskcc.org.
authors: Craig B
authors: CB
authors: Thompson
mesh_terms: D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005462:Fluorine Radioisotopes / Q000378:metabolism* / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D005973:Glutamine / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D049268:Positron-Emission Tomography
chemical_list: D005462:Fluorine Radioisotopes; D005973:Glutamine