title: Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.
abstract: Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor.
  
  
  METHODS
  We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses.
  
  
  RESULTS
  The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain).
  
  
  CONCLUSIONS
  These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle 98195, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Spence
authors.forename: M
authors.initials: M
authors.lastname: Muzi
authors.forename: M M
authors.initials: MM
authors.lastname: Graham
authors.forename: F
authors.initials: F
authors.lastname: O'Sullivan
authors.forename: K A
authors.initials: KA
authors.lastname: Krohn
authors.forename: J M
authors.initials: JM
authors.lastname: Link
authors.forename: T K
authors.initials: TK
authors.lastname: Lewellen
authors.forename: B
authors.initials: B
authors.lastname: Lewellen
authors.forename: S D
authors.initials: SD
authors.lastname: Freeman
authors.forename: M S
authors.initials: MS
authors.lastname: Berger
authors.forename: G A
authors.initials: GA
authors.lastname: Ojemann
mesh_terms: D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D015173:Supratentorial Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose