Precise dose verification in proton therapy via F-18 activation measured with positron emission tomography imaging

Objective.To verify the delivered dose in proton therapyin vivousing positron emission tomography (PET) with millimetric precision.Approach.Proton and ion therapy have gained significant importance in cancer radiotherapy due to their favorable dose distribution and tissue-sparing properties. In conventional gamma radiation therapy some methods ofin vivodose verification are possible with current medical devices. In proton and ion therapy, dose verification is limited, with PET being mainly used for particle range assessments rather than full dose mapping. Prompt gamma techniques are well suited for range verification but are not suitable for full three-dimensional (3D), voxel-wise dose mapping. This study presents initial results forin vivodose verification using F-18 PET imaging during proton therapy. Although the activity concentration of F-18 generated by typical clinical doses (several Gy) is low, PET imaging performed approximately one-hour post-irradiation yields sufficient image quality to derive dose-volume histograms (DVHs), enabling spatial dose verification. We simulated proton treatment in a brain phantom using the Gate and RayStation platforms to assess the production of several positron emitting isotopes. We focused on the production of fluorine-18 (F-18), given its low positron energy and low energy threshold for production, which enables accurate replication of the dose distribution. To evaluate the detectability of the anticipated low activity concentrations (on the order of a fraction of a Bq ml^-1) following a 3 Gy proton irradiation, we tested three PET systems: two preclinical scanners based on LYSO detectors and one clinical scanner based on BGO crystals. Finally, we analyzed the DVHs for the simulated and measured dose and activity distributions and compared them with the planned distribution.Main Results.F-18 PET imaging in proton therapy correlates with the delivered dose to within 5% and matches the planned dose fall-off edge within 1 mm, enabling accurate and precisein vivodose verification.Significance.F-18 enables more accurate proton-therapy dose verification than other positron emitters studied (C-11, N-13, and O-15), showing the closest spatial correspondence to the planned dose and activity levels post-therapy that remain detectable on modern BGO-based PET systems.