title: Assessment of tumor hypoxia by 62Cu-ATSM PET/CT as a predictor of response in head and neck cancer: a pilot study.
abstract: OBJECTIVE
  In radiotherapy and chemotherapy tumor hypoxia is recognized as a major obstacle to effective treatment. We undertook a pilot study in patients with locally advanced head and neck cancer to determine whether there is a relationship between tumor uptake of (62)Cu-ATSM and response to chemoradiotherapy.
  
  
  METHODS
  Seventeen patients were studied using PET/CT with (62)Cu-ATSM and (18)F-FDG prior to the initiation of radiotherapy and chemotherapy. All patients had locally advanced head and neck cancer (stage III or IV). Tumor uptake in all patients was measured by region of interest analysis using the maximal standardized uptake value (SUVmax). A total dose of 50.4-70.2 Gy (median 70.2 Gy) was delivered in 29-39 fractions (median 39 fractions) to tumor. In patients with (non CR) and without (CR) residual/recurrent tumors at 2-year post irradiation, the statistical significance of the differences in tumor (62)Cu-ATSM SUVmax, T/M ratio, (18)F-FDG SUVmax and tumor volume were analyzed using Student's t test and Welch test. The relationship between clinical outcome and (62)Cu-ATSM/(18)F-FDG uptake patterns was analyzed using Kruskal-Wallis test. The correlation between SUVmax of (62)Cu-ATSM and (18)F-FDG was compared by Spearman's rank correlation test.
  
  
  RESULTS
  Two of the 17 patients that were enrolled in our study were excluded from the final analysis. Of the 15 remaining patients, 9 patients were free of disease and 6 patients had residual/recurrent tumors. The SUVmax differed significantly (p < 0.05) between patients with or without residual/recurrent tumor on (62)Cu-ATSM PET/CT. Six of the 10 patients with tumors SUVmax >5.00 had residual/recurrent tumor, whereas all of the 5 patients with tumors SUVmax <5.00 were free of disease. There was no significant difference in FDG uptake between patients with and without residual/recurrent tumor.
  
  
  CONCLUSIONS
  The results of this pilot study suggested that (62)Cu-ATSM uptake may be a predictive indicator of tumor response to chemoradiotherapy in patients with locally advanced head and neck cancer.
authors.affiliation: Department of Radiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Minagawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shizukuishi
authors.forename: Izumi
authors.initials: I
authors.lastname: Koike
authors.forename: Choichi
authors.initials: C
authors.lastname: Horiuchi
authors.forename: Kei
authors.initials: K
authors.lastname: Watanuki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hata
authors.forename: Motoko
authors.initials: M
authors.lastname: Omura
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Odagiri
authors.forename: Iwai
authors.initials: I
authors.lastname: Tohnai
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
authors.forename: Ukihide
authors.initials: U
authors.lastname: Tateishi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000378:metabolism; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D013882:Thiosemicarbazones / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)