A prospective clinical trial of tumor hypoxia imaging with 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) before and during radiation therapy

Abstract

To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), (18)F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (≥1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of ≥1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO ≥1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of ≥1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0-0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT.

Keywords: 18F-misonidazole; PET/CT; reoxygenation; tumor hypoxia.

Fig. 1.

F-MISO PET/CT (a, c), and FDG PET/CT (b, d) for a patient with nasopharyngeal cancer (case 8: T1N2bM0). In this patient, no significant F-MISO accumulation was observed in the primary tumor (SUVmax; 1.20) or metastatic lymph nodes (1.35), although strong FDG uptake was noted.

Fig. 2.

Changes in F-MISO SUVmax and T/M ratios for eight patients. Six of the eight tumors showed a decrease in SUVmax and/or the T/M ratio after approximately 20 Gy of fractionated RT.

Fig. 3.

F-MISO PET/CT (a) before RT, and (b) during RT (18 Gy/10 fractions), for a patient with anal canal squamous cell carcinoma (case 7: T2N0M0). In this patient, F-MISO accumulation in the primary tumor (SUVmax; 2.44) decreased to 2.08 in the second F-MISO study at 18 Gy/10 fractions.