Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo Journal Article


Authors: Venneti, S.; Dunphy, M. P.; Zhang, H. W.; Pitter, K. L.; Zanzonico, P.; Campos, C.; Carlin, S. D.; La Rocca, G.; Lyashchenko, S.; Ploessl, K.; Rohle, D.; Omuro, A. M.; Cross, J. R.; Brennan, C. W.; Weber, W. A.; Holland, E. C.; Mellinghoff, I. K.; Kung, H. F.; Lewis, J. S.; Thompson, C. B.
Article 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 F-18-fluorodeoxyglucose (F-18-FDG). However, F-18-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-F-18-(2S, 4R)-fluoroglutamine (F-18-FGln) shows high uptake in gliomas but low background brain uptake, facilitating clear tumor delineation. Chemo/radiation therapy reduced F-18-FGln tumor avidity, corresponding with decreased tumor burden. F-18-FGln uptake was not observed in animals with a permeable blood-brain barrier or neuroinflammation. We translated these findings to human subjects, where F-18-FGln showed high tumor/background ratios with minimal uptake in the surrounding brain in human glioma patients with progressive disease. These data suggest that F-18-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.
Keywords: reveals; cells; growth; blood-brain-barrier; tumor metabolism; x(c)(-) transporter activity
Journal Title: Science Translational Medicine
Volume: 7
Issue: 274
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2015-02-11
Start Page: 274ra17
Language: English
ACCESSION: WOS:000349702200005
DOI: 10.1126/scitranslmed.aaa1009
PROVIDER: wos
PUBMED: 25673762
PMCID: PMC4431550
Notes: Article -- 274ra17 -- Source: Wos
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Cameron Brennan
    226 Brennan
  2. Antonio Marcilio Padula Omuro
    204 Omuro
  3. Mark Phillip Dunphy
    81 Dunphy
  4. Pat B Zanzonico
    355 Zanzonico
  5. Hanwen Zhang
    34 Zhang
  6. Jason S Lewis
    456 Lewis
  7. Sean Denis Carlin
    83 Carlin
  8. Justin Robert Cross
    111 Cross
  9. Ken L Pitter
    53 Pitter
  10. Daniel A Rohle
    14 Rohle
  11. Carl Campos
    37 Campos
  12. Craig Bernie Thompson
    153 Thompson
  13. Wolfgang Andreas Weber
    173 Weber