Measurement of Tumor Hypoxia in Patients With Locally Advanced Cervical Cancer Using Positron Emission Tomography with ¹⁸F-Fluoroazomyin Arabinoside.

Abstract

To assess cervical tumor hypoxia using the hypoxia tracer ¹⁸F-fluoroazomycin arabinoside (¹⁸F-FAZA) and compare different reference tissues and thresholds for quantifying tumor hypoxia. Twenty-seven patients with cervical cancer were studied prospectively by positron emission tomography (PET) imaging with ¹⁸F-FAZA before starting standard chemoradiation. The hypoxic volume was defined as all voxels within a tumor (T) with standardized uptake values (SUVs) greater than 3 standard deviations from the mean gluteus maximus muscle SUV value (M) or SUVs greater than 1 to 1.4 times the mean SUV value of the left ventricle, a blood (B) surrogate. The hypoxic fraction was defined as the ratio of the number of hypoxic voxels to the total number of tumor voxels. A ¹⁸F-FAZA-PET hypoxic volume could be identified in the majority of cervical tumors (89% when using T/M or T/B > 1.2 as threshold) on the 2-hour static scan. The hypoxic fraction ranged from 0% to 99% (median 31%) when defined using the T/M threshold and from 0% to 78% (median 32%) with the T/B > 1.2 threshold. Hypoxic volumes derived from the different thresholds were highly correlated (Spearman's correlation coefficient ρ between T/M and T/B > 1-1.4 were 0.82-0.91), as were hypoxic fractions (0.75-0.85). Compartmental analysis of the dynamic scans showed k₃, the FAZA accumulation constant, to be strongly correlated with hypoxic fraction defined using the T/M (Spearman's ρ=0.72) and T/B > 1.2 thresholds (0.76). Hypoxia was detected in the majority of cervical tumors on ¹⁸F-FAZA-PET imaging. The extent of hypoxia varied markedly between tumors but not significantly with different reference tissues/thresholds.