title: Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.
abstract: PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non-small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of (18)F-Fluoromisonidazole ((18)F-FMISO), and to examine the relationship of hypoxia to the uptake of (18)F-FDG, microvessel density, and other molecular markers of hypoxia.
  
  
  METHODS
  Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with (18)F-FMISO and (18)F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia.
  
  
  RESULTS
  In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51-77 y), the mean (18)F-FMISO uptake in tumor was significantly lower than that of (18)F-FDG uptake (P < 0.0001) and showed no correlation with (18)F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) (18)F-FMISO SUV(max) (maximum standardized uptake value) was 1.20 [0.95-1.45] compared with the mean [95% CI] (18)F-FDG SUV(max) of 5.99 [4.62-7.35]. The correlation between (18)F-FMISO uptake, (18)F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between (18)F-FMISO and (18)F-FDG uptake and Ki67 was found.
  
  
  CONCLUSIONS
  The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by (18)F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.
authors.affiliation: Centre for PET, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Cherk
authors.forename: Serene S
authors.initials: SS
authors.lastname: Foo
authors.forename: Aurora M T
authors.initials: AM
authors.lastname: Poon
authors.forename: Simon R
authors.initials: SR
authors.lastname: Knight
authors.forename: Carmel
authors.initials: C
authors.lastname: Murone
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.forename: John I
authors.initials: JI
authors.lastname: Sachinidis
authors.forename: Timothy H C
authors.initials: TH
authors.lastname: Saunder
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: O'Keefe
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D015687:Cell Hypoxia; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013223:Statistics as Topic
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole; D005947:Glucose