Assessing Tumor Hypoxia in Cervical Cancer by PET with ⁶⁰Cu-Labeled Diacetyl-Bis(N⁴-Methylthiosemicarbazone)

¹ Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri; Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri
² Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; Department of Radiation Oncology, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri
³ Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri
⁴ Division of Nuclear Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri; Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri

^* To whom correspondence should be addressed. E-mail: dehdashtif{at}mir.wustl.edu.

	Abstract

Tumor hypoxia indicates a poor prognosis. This study was undertaken to confirm our prior pilot results showing that pretreatment tumor hypoxia demonstrated by PET with ⁶⁰Cu-labeled diacetyl-bis(N⁴-methylthiosemicarbazone) (⁶⁰Cu-ATSM) is a biomarker of poor prognosis in patients with cervical cancer. Thirty-eight women with biopsy-proved cervical cancer underwent ⁶⁰Cu-ATSM PET before the initiation of radiotherapy and chemotherapy. ⁶⁰Cu-ATSM uptake was evaluated semiquantitatively as the tumor-to-muscle activity ratio (T/M). A log-rank test was used to determine the cutoff uptake value that was strongly predictive of prognosis. All patients also underwent clinical PET with ¹⁸F-FDG before the institution of therapy. The PET results were correlated with clinical follow-up. Tumor ⁶⁰Cu-ATSM uptake was inversely related to progression-free survival and cause-specific survival (P = 0.006 and P = 0.04, respectively, as determined by the log-rank test). We found that a T/M threshold of 3.5 best discriminated patients likely to develop a recurrence from those unlikely to develop a recurrence; the 3-y progression-free survival of patients with normoxic tumors (as defined by T/M of 3.5) was 71%, and that of patients with hypoxic tumors (T/M of >3.5) was 28% (P = 0.01). Tumor ¹⁸F-FDG uptake did not correlate with ⁶⁰Cu-ATSM uptake, and there was no significant difference in tumor ¹⁸F-FDG uptake between patients with hypoxic tumors and those with normoxic tumors (P = 0.9). Pretherapy ⁶⁰Cu-ATSM PET provides clinically relevant information about tumor oxygenation that is predictive of outcome in patients with cervical cancer.

Key Words: PET, ⁶⁰Cu-ATSM, hypoxia, cervical cancer, survival

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