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

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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.