High Reproducibility of Tumor Hypoxia Evaluated by ¹⁸F-Fluoromisonidazole PET for Head and Neck Cancer

Abstract

Tumor hypoxia is well known to be radiation resistant. ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) PET has been used for noninvasive evaluation of hypoxia. Quantitative evaluation of ¹⁸F-FMISO uptake is thus expected to play an important role in the planning of dose escalation radiotherapy. However, the reproducibility of ¹⁸F-FMISO uptake has remained unclarified. We therefore investigated the reproducibility of tumor hypoxia by using quantitative analysis of ¹⁸F-FMISO uptake. Methods: Eleven patients with untreated head and neck cancer underwent 2 ¹⁸F-FMISO PET/CT scans (¹⁸F-FMISO₁ and ¹⁸F-FMISO₂) with a 48-h interval prospectively. All images were acquired at 4 h after ¹⁸F-FMISO injection for 10 min. The maximum standardized uptake (SUVmax), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of ¹⁸F-FMISO uptake were statistically compared between the 2 ¹⁸F-FMISO scans by use of intraclass correlation coefficients (ICCs). The hypoxic volume was calculated as the area with a TBR of greater than or equal to 1.5 or the area with a TMR of greater than or equal to 1.25 to assess differences in hypoxic volume between the 2 ¹⁸F-FMISO scans. The distances from the maximum uptake locations of the ¹⁸F-FMISO₁ images to those of the ¹⁸F-FMISO₂ images were measured to evaluate the locations of ¹⁸F-FMISO uptake. Results: The SUVmax (mean ± SD) for ¹⁸F-FMISO₁ and ¹⁸F-FMISO₂ was 3.16 ± 1.29 and 3.02 ± 1.12, respectively, with the difference between the 2 scans being 7.0% ± 4.6%. The TBRs for ¹⁸F-FMISO₁ and ¹⁸F-FMISO₂ were 2.98 ± 0.83 and 2.97 ± 0.64, respectively, with a difference of 9.9% ± 3.3%. The TMRs for ¹⁸F-FMISO₁ and ¹⁸F-FMISO₂ were 2.25 ± 0.71 and 2.19 ± 0.67, respectively, with a difference of 7.1% ± 5.3%. The ICCs for SUVmax, TBR, and TMR were 0.959, 0.913, and 0.965, respectively. The difference in hypoxic volume based on TBR was 1.8 ± 1.8 mL, and the difference in hypoxic volume based on TMR was 0.9 ± 1.3 mL, with ICCs of 0.986 and 0.996, respectively. The maximum uptake locations of the ¹⁸F-FMISO₁ images were different from those of the ¹⁸F-FMISO₂ images and were within the full width at half maximum of the PET/CT scanner, except in 1 case. Conclusion: The values for ¹⁸F-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 ¹⁸F-FMISO scans were highly reproducible. Such high reproducibility of tumor hypoxia is promising for accurate radiation planning.