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-1a, which is a composition of HIF-1. However, it is unclear whether 18 F-FMISO PET can identify HIF-1a expression in oral squamous cell carcinoma (OSCC). The present study was performed to elucidate the correlation between 18 F-FMISO PET findings and HIF-1a expression in OSCC. Methods: 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-1a expression in the operation materials was evaluated by immunohistochemical staining. The SUV max of both PET studies and HIF-1a findings were compared statistically. Results: 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 5 0.02, r 5 0.48). HIF-1a expression was clearly detected in 11 of the 23 patients (48%). The 18 F-FMISO PET SUV max was significantly higher in the HIF-1a-positive cases than in the HIF-1a-negative cases (median, 2.1; range, 1.5-2.4, vs. median, 1.6; range, 0.8-2.0, respectively) (P 5 0.002). However, there were no significant correlations between 18 F-FDG PET SUV max and HIF-1a expression (median, 21.8; range, 7.7-29.1 vs. 1.0-32.2) (P 5 0.06). Conclusion: 18 F-FMISO uptake in the primary site of OSCC indicates a hypoxic environment with HIF-1a expression.

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy

“…This is not surprising, because Sato et al reported that the FMISO uptake was weakly correlated with the FDG uptake. However, FDG-PET findings do not provide enough information for evaluating reoxygenation in hypoxic tumors, although they can indicate the metabolic activity [6]. Therefore, FDG-PET is not an alternative to FMISO-PET for this purpose.…”

“…F-18 fluoromisonidazole positron emission tomography (FMISO-PET) has been used for noninvasive evaluations of hypoxia, and the FMISO uptake was demonstrated to be correlated with uptake of pimonidazole in animal glioma and with hypoxia-inducible factor-1α (HIF1α) expression in human oral squamous cell carcinoma [5,6]. Several reports have proposed that FMISO uptake is related to patient prognoses [7][8][9][10].…”

Positron emission tomography to assess hypoxia and perfusion in lung cancer

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Radiotherapy response evaluation using FDG PET-CT—established and emerging applications

“…Tumour hypoxia is known to promote radiotherapy resistance. 75 Fluorine-18 fluoromisonidazole has been widely researched and demonstrated to accumulate in hypoxic cells in head and neck, 76 brain 77 and lung 78 tumours, but its clinical application is limited by a high signal-to-noise ratio. Alternative tracers which act as surrogates for hypoxia include fluorine-18 fluoroazomycin-arabinofuranoside and copper-64 diacetyl-bis(N4-methylthiosemicarbazone).…”