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), 18F-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.

Feasibility and repeatability of PET with the hypoxia tracer [18F]HX4 in oesophageal and pancreatic cancer

“…Thus, for monitoring of treatment response, effects must induce a greater change than this to be detectable. Studies investigating dynamics of hypoxic areas before and during (chemo)radiation suggest that hypoxia indeed changes in the course of treatment and moreover, residual hypoxia after the first courses of treatment has a higher prognostic value than baseline hypoxia [26,[42][43][44][45][46]. The normal variation in [ 18 F]HX4 uptake we found in this study was lower than the changes found during treatment, suggesting it to be able to assess these changes and thus as a potential tool for early response evaluation.…”

Positron emission tomography to assess hypoxia and perfusion in lung cancer

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

“…Several studies using an animal model observed reoxygenation after fractionated radiation and the efficacy of dose escalation [15][16][17][18][19]. A number of other studies reported a reduction of FMISO uptake in hypoxic tumors during or after radiation therapy [20][21][22][23][24][25]. On the other hand, the tumoricidal effect during radiation also affects FMISO-PET results.…”

“…Tumor cells that have been killed by irradiation no longer exhibit tumor hypoxia. However, the abovementioned reports [20][21][22][23][24][25] did not discuss the tumoricidal effect, and it is thus difficult to reach any conclusions regarding whether the reduction of FMISO uptake during radiotherapy is due to reoxygenation or to the tumoricidal effect. In order to confirm the occurrence of reoxygenation due to radiotherapy, comparisons of hypoxic changes and tumoricidal effects are necessary.…”