18F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma

Abstract

Hypoxia is a common feature of cancer and a prognostic factor for many types of cancer. (18)F-fluoromisonidazole ((18)F-FMISO) PET can detect tumor hypoxia noninvasively. Hypoxia-inducible factor-1 (HIF-1) is a key player in the transcriptional response to low oxygen tension in many types of cancer. Its activity is mainly dependent on the stability and modification of HIF-1α, which is a composition of HIF-1. However, it is unclear whether (18)F-FMISO PET can identify HIF-1α expression in oral squamous cell carcinoma (OSCC). The present study was performed to elucidate the correlation between (18)F-FMISO PET findings and HIF-1α expression in OSCC. Twenty-three patients (age range, 42-84 y; 15 men, 8 women) with OSCC were enrolled in this study. The T-stages of cancer were T1 in 1 patient, T2 in 9, T3 in 2, and T4a in 11. The N-stages were N0 in 13 patients, N1 in 5, and N2 in 5. Each patient underwent (18)F-FMISO and (18)F-FDG PET before surgery, and the maximum standardized uptake value (SUV max) of both PET studies was measured. HIF-1α expression in the operation materials was evaluated by immunohistochemical staining. The SUV max of both PET studies and HIF-1α findings were compared statistically. (18)F-FMISO PET detected uptake in the primary site in 14 of the 23 patients (61%). The median SUV max of (18)F-FMISO and (18)F-FDG PET in the primary site was 1.83 (range, 0.8-2.7) and 16.5 (range, 1.0-32.3), respectively. There was a weak significant correlation between (18)F-FMISO and (18)F-FDG PET SUV max (P = 0.02, r = 0.48). HIF-1α expression was clearly detected in 11 of the 23 patients (48%). The (18)F-FMISO PET SUV max was significantly higher in the HIF-1α-positive cases than in the HIF-1α-negative cases (median, 2.1; range, 1.5-2.4, vs. median, 1.6; range, 0.8-2.0, respectively) (P = 0.002). However, there were no significant correlations between (18)F-FDG PET SUV max and HIF-1α expression (median, 21.8; range, 7.7-29.1 vs. 1.0-32.2) (P = 0.06). (18)F-FMISO uptake in the primary site of OSCC indicates a hypoxic environment with HIF-1α expression.