Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET

PLoS One. 2016 May 17;11(5):e0155635. doi: 10.1371/journal.pone.0155635. eCollection 2016.

Abstract

Purpose: Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG).

Methods: Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method.

Results: The means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively).

Conclusion: Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Aged
  • Coordination Complexes
  • Copper Radioisotopes*
  • Female
  • Fluorine Radioisotopes
  • Fluorodeoxyglucose F18
  • Head and Neck Neoplasms / diagnostic imaging*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Male
  • Organometallic Compounds*
  • Oxidation-Reduction
  • Positron-Emission Tomography / methods*
  • Predictive Value of Tests
  • Prognosis
  • Thiosemicarbazones*

Substances

  • Coordination Complexes
  • Copper Radioisotopes
  • Fluorine Radioisotopes
  • Organometallic Compounds
  • Thiosemicarbazones
  • copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)
  • Fluorodeoxyglucose F18

Grants and funding

This study was partly funded by the grants-in-aid for scientific research from the Japan Society for the Promotion of Science (21390342, 24249065, 16K10345) and the Japan Advanced Molecular Imaging Program (J-AMP). HO and TTsujikawa received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.