Comparison of molecular markers of hypoxia and imaging with 60Cu-ATSM in cancer of the uterine cervix

Purpose: To determine if hypoxia-related molecular markers are associated with Cu-60 labeled diacetyl-bis (N-4-methylthiosemicarbazone); (Cu-60-ATSM) imaging of tumor hypoxia in cervical cancer. Procedures: Fifteen patients were enrolled in a prospective study and underwent evaluation of tumor hypoxia with positron emission tomography (PET) using Cu-60-ATSM. Cu-60-ATSM-PET imaging was compared with the expression of tissue molecular markers, which included vascular endothelial growth factor (VEGF), cyclo-oxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), carbonic anyhdrase IX (CA-9), and apoptotic index. Reuslts: Six patients had hypoxic tumors determined by Cu-60-ATSM, and nine had non-hypoxic tumors. The 4-year overall survival estimates were 75% for patients with non-hypoxic tumors and 33% for those with hypoxic tumors (p=0.04). Overexpression of VEGF (p=0.13), EGFR (p=0.05), CA-9 (p=0.02), COX-2 (p=0.08), and the presence of apoptosis (p=0.005) occurred in patients with hypoxic tumors. Cox proportional hazards modeling demonstrated hypoxia as determined by Cu-60-ATSM to be a significant independent predictor of tumor recurrence (p=0.0287). Conclusions: Cu-60-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.