¹⁸F-Fluoroazomycin Arabinoside (FAZA) PET/MR as a Biomarker of Hypoxia in Rectal Cancer: A Pilot Study

Tumor hypoxia is a negative prognostic factor in many tumors and is predictive of metastatic spread and poor responsiveness to both chemotherapy and radiotherapy. Purpose: To assess the feasibility of using ¹⁸F-Fluoroazomycin arabinoside (FAZA) PET/MR to image tumor hypoxia in patients with locally advanced rectal cancer (LARC) prior to and following neoadjuvant chemoradiotherapy (nCRT). The secondary objective was to compare different reference tissues and thresholds for tumor hypoxia quantification. Patients and Methods: Eight patients with histologically proven LARC were included. All patients underwent ¹⁸F-FAZA PET/MR prior to initiation of nCRT, four of whom also had a second scan following completion of nCRT and prior to surgery. Tumors were segmented using T₂-weighted MR. Each voxel within the segmented tumor was defined as hypoxic or oxic using thresholds derived from various references: ×1.0 or ×1.2 SUVmean of blood pool [BP] or left ventricle [LV] and SUVmean +3SD for gluteus maximus. Correlation coefficient (CoC) between HF and tumor SUVmax/reference SUVmean TRR for the various thresholds was calculated. Hypoxic fraction (HF), defined as the % hypoxic voxels within the tumor volume was calculated for each reference/threshold. Results: For all cases, baseline and follow-up, the CoCs for gluteus maximus and for BP and LV (×1.0) were 0.241, 0.344, and 0.499, respectively, and HFs were (median; range) 16.6% (2.4-33.8), 36.8% (0.3-72.9), and 30.7% (0.8-55.5), respectively. For a threshold of ×1.2, the CoCs for BP and LV as references were 0.611 and 0.838, respectively, and HFs were (median; range) 10.4% (0-47.6), and 4.3% (0-20.1%), respectively. The change in HF following nCRT ranged from (-18.9%) to (+54%). Conclusions: Imaging of hypoxia in LARC with ¹⁸F-FAZA PET/MR is feasible. Blood pool as measured in the LV appears to be the most reliable reference for calculating the HF. There is a wide range of HF and variable change in HF before and after nCRT.