Parametric Imaging of Washout In Range‑Verification Open PET: Clinical Demonstration of Tumor Diagnosis during Carbon‑Ion Therapy
Abstract
Purpose
Tumor oxygenation plays a critical role in treatment response and progression. However, repeating PET with hypoxia-specific radioligands at every treatment fraction is not practical. Tumor-vascular status, by contrast, can be assessed by measuring the washout-rates of irradiation-induced positron emitters using range-verification PET. We therefore hypothesized that vascular status may serve as an indirect indicator of tumor hypoxia. In the last AAPM, we reported a clear correlation between washout‑rate maps and 18F‑FAZA hypoxia PET in a carbon-ion irradiation study with tumor-bearing rats. In this study, we aimed to demonstrate washout-based tumor diagnosis in patients.
Methods
The world’s first open-type PET system, OpenPET, was installed in a fixed-beam treatment room at HIMAC (as reported in AAPM2025), and a clinical study of range-verification for carbon‑ion therapy was conducted (jRCTs032220746). Patients with H&N cancer received a total of 64 Gy (RBE-weighted) in 16 fractions over 4-weeks. Range-verification OpenPET acquisition was performed for 10 minutes immediately after horizontal-beam irradiation. The washout-rate constant (k₂) was estimated on a voxel-wise.
Results
Range-verification OpenPET images were consistent with the treatment plan throughout the 4‑week course. By contrast, the voxel-wise k₂‑map exhibited week-to-week variations, suggesting changes in tumor vascular status. In some cases, regions with slow washout early in treatment had disappeared in the later phase. Considering our rat study where hypoxic regions exhibited slower washout because vasculature was insufficient to deliver oxygen, the finding may be explained by initial hypoxic areas being re-perfused in response to radiotherapy.
Conclusion
A clinical trial of parametric imaging with range‑verification OpenPET during carbon‑ion therapy was conducted, and changes in the washout-rate map were observed in accordance with the progression of radiation delivery. Our future work is to analyze clinical data from up to 20 additional patients and to investigate the relationship between temporal changes in the washout-rate map and follow‑up outcomes.