title: Assessing tumor hypoxia in head and neck cancer by PET with ⁶²Cu-diacetyl-bis(N⁴-methylthiosemicarbazone).
abstract: OBJECTIVE
  The aim of this study was to investigate the potential of PET imaging with a hypoxia-selective tracer ⁶²Cu-diacetyl-bis(N⁴-methylthiosemicarbazone) (⁶²Cu-ATSM) for evaluating the prognosis of patients with head and neck cancer (HNC).
  
  
  METHODS
  Twenty-five patients with HNC including stage II to IV underwent both ⁶²Cu-ATSM and ¹⁸F-FDG PET before the initiation of treatment. Volumes of interest were placed on the tumor and sternocleidomastoid muscles to obtain SUVmax and to calculate the tumor-to-muscle activity ratio (TMR). The PET results were correlated with clinical follow-up, and the receiver operating characteristic analysis was used to determine the optimal cutoff values. Progression-free survival (PFS) and cause-specific survival (CSS) were statistically analyzed.
  
  
  RESULTS
  Patients were followed up for periods ranging from 4 to 32 months. Twelve patients died from local recurrence or metastasis of a primary cancer, and 2 had recurrence of the 13 remaining patients. Mean (SD) periods of PFS and CSS were 15.5 (12.5) and 18.6 (11.0) months, respectively. Optimal cutoff values for each PET index were as follows: SUVs of ⁶²Cu-ATSM (SUVATSM) and FDG were 3.6 and 7.9; TMRs of ATSM (TMRATSM) and FDG were 3.2 and 5.6. When the cutoff for TMRATSM was set at 3.2, patients with a greater TMRATSM had significantly worse PFS (P = 0.014) and CSS (P = 0.031). Two-year PFS and CSS rates were 73% and 80% for patients with a lower TMRATSM (≤3.2); however, they were 20% and 33% for those with hypoxic tumors (TMRATSM, >3.2), respectively. F-FDG-related indices did not show any significant difference in either PFS or CSS.
  
  
  CONCLUSIONS
  Pretreatment ⁶²Cu-ATSM PET is useful for predicting the prognosis of patients with HNC.
authors.affiliation: From the *Biomedical Imaging Research Center, Departments of †Radiology, and ‡Otolaryngology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Myungmi
authors.initials: M
authors.lastname: Oh
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Kimura
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009942:Organometallic Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D000077195:Squamous Cell Carcinoma of Head and Neck; D013882:Thiosemicarbazones
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)