title: Prognostic significance of hypoxic PET using (18)F-FAZA and (62)Cu-ATSM in non-small-cell lung cancer.
abstract: OBJECTIVE
  Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) (n=45) and/or (62)Cu-diacetyl-bis (N4)-methylsemithiocarbazone ((62)Cu-ATSM) (n=22). All received (18)F-fluorodeoxyglucose ((18)F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively.
  
  
  RESULTS
  A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of (18)F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs ((18)F-FAZA, p<0.01; (62)Cu-ATSM, p<0.04), but not with that of (18)F-FDG. The patients with a higher accumulation had significantly poorer overall survival [(18)F-FAZA, HR (hazard ratio), 9.50, p<0.01; (62)Cu-ATSM, HR, 4.06, p<0.05] and progression free survival ((18)F-FAZA, HR, 5.28, p<0.01, (62)Cu-ATSM, HR, 2.72, p<0.05).
  
  
  CONCLUSIONS
  Both (18)F-FAZA and (62)Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan. Electronic address: t.kinoshita.a7@keio.jp.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Functional Imaging Division, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kamiyama
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohtsuka
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Asamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000502:physiology*; D056831:Coordination Complexes; D019008:Drug Resistance, Neoplasm; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000032:analysis; D009942:Organometallic Compounds / Q000032:analysis*; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000032:analysis*; D012189:Retrospective Studies; D016019:Survival Analysis; D013882:Thiosemicarbazones / Q000032:analysis*
chemical_list: D056831:Coordination Complexes; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); D019788:Fluorodeoxyglucose F18; C498052:fluoroazomycin arabinoside
keywords: (18)F-fluoroazomycin arabinoside; (18)F-fluorodeoxyglucose; (62)Cu-diacetyl-bis (N4)-methylsemithiocarbazone; Hypoxic positron emission tomography; Non-small-cell lung cancer; Prognostic factor