Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report

Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1233-8. doi: 10.1016/s0360-3016(02)04477-2.

Abstract

Purpose: Tumor hypoxia is associated with poor response to therapy. We have investigated whether pretreatment tumor hypoxia assessed by positron emission tomography (PET) with Cu-60 diacetyl-bis(N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) predicts responsiveness to subsequent therapy in cervical cancer.

Methods and materials: Fourteen patients with biopsy-proved cervical cancer were studied by PET with (60)Cu-ATSM before initiation of radiotherapy and chemotherapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M) and peak slope index of tumor tracer uptake. All patients also underwent clinical PET with F-18 fluorodeoxyglucose (FDG) before institution of therapy. The PET results were correlated with follow-up evaluation (14-24 months).

Results: Tumor uptake of (60)Cu-ATSM was inversely related to progression-free survival and overall survival (log-rank p = 0.0005 and p = 0.015, respectively). An arbitrarily selected T/M threshold of 3.5 discriminated those likely to develop recurrence; 6 of 9 patients with normoxic tumors (T/M < 3.5) are free of disease at last follow-up, whereas all of 5 patients with hypoxic tumors (T/M > 3.5) have already developed recurrence. Similar discrimination was achieved with the peak slope index. The frequency of locoregional nodal metastasis was greater in hypoxic tumors (p = 0.03). Tumor FDG uptake did not correlate with (60)Cu-ATSM uptake (r = 0.04; p = 0.80), and there was no significant difference in tumor FDG uptake between patients with hypoxic tumors and those with normoxic tumors.

Conclusion: (60)Cu-ATSM-PET in patients with cervical cancer revealed clinically relevant information about tumor oxygenation that was predictive of tumor behavior and response to therapy in this small study.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Hypoxia*
  • Combined Modality Therapy
  • Copper Radioisotopes*
  • Disease-Free Survival
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Follow-Up Studies
  • Humans
  • Image Processing, Computer-Assisted
  • Life Tables
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Organometallic Compounds*
  • Prospective Studies
  • Radiation Tolerance
  • Radiopharmaceuticals*
  • Survival Rate
  • Thiosemicarbazones*
  • Tomography, Emission-Computed*
  • Treatment Outcome
  • Uterine Cervical Neoplasms / diagnostic imaging*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / radiotherapy

Substances

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