Range verification in particle therapy: development and characterization of in-beam PET and PGT systems

Particle therapy offers superior radiation treatment through highly conformal dose delivery, characterized by the distinct Bragg peak of charged particles. However, this physical advantage is also a vulnerability, as range differences caused by anatomical changes or patient positioning can compromise treatment accuracy. To fully exploit the dosimetric advantage of the Bragg peak, detector systems capable of real-time range verification are required. This thesis presents the analysis and preliminary performance assessment of standalone range verification prototypes developed within the framework of the INFN Superconducting Ion Gantry (SIG) project, investigating three distinct approaches: in-beam Positron Emission Tomography (PET), Prompt Gamma Timing (PGT), and Prompt Photons monitoring with a Cherenkov-based detection system. First, the imaging performance of a custom-made in-beam PET prototypewas evaluated for carbon-ion therapy at the Italian Center of Oncological Hadrontherapy (CNAO). Carbon-ion monitoring is particularly challenging due to the low statistics associated with the reduced number of primary particles delivered in therapeutic condition and the relatively long decay time of the radioisotopes produced with respect to proton treatments. A dedicated statistical analysis was performed to study the stability of the activation peak mainly corresponding to 11C decays (due to projectile fragmentation) and range difference estimation under low-counting conditions. The results demonstrate that the projectile-fragmentation peak is a strong range marker and that, for 500 coincidences—corresponding to less than 2 s of inter-spill acquisition time—the estimated range difference agrees with the expected value within about 2 mm. Second, the first prompt gamma timing (PGT) measurements were investigated experimentally with carbon-ion beams atCNAOusing a dedicated setup composed of a silicon strip sensor for primary ions and a fast LaBr3:Ce–SiPM detector for secondary radiation. Different phantom geometries (including air gaps and a bone-equivalent insert), beam energies, and secondary radiation detector positions were studied to quantify the timing performance and evaluate sensitivity to range perturbations. Notably, the analysis demonstrated that the system could successfully resolve time-distribution shifts caused by 2 cm and 4 cm air gaps, observing statistically significant deviations from the homogeneous baseline. Experimental results were supported by Geant4 Monte Carlo simulations to assess the reliability and interpretation of the measured PGT differences. Future work will investigate smaller heterogeneities under more clinically realistic irradiation conditions. Finally, a Monte Carlo simulation study of a Cherenkov-based secondary radiation detector was performed using the GATE toolkit to investigate the feasibility of a Prompt Photon detection system for proton range verification. In this study, a lead fluoride (PbF2) crystal was considered and its response curve in terms of number of Cherenkov photons emitted as a function of the released energy was studied with monoenergetic gamma source and clinical-like secondary photon emission. The simulations predicted an average yield of 58 detected Cherenkov photons per incident prompt gamma, with an approximately linear response over the clinically relevant energy range of 2.3–6.1 MeV. The study quantified the energy-dependent Cherenkov light yield and identified the dominant interaction mechanisms in the radiator, supporting the potential of Cherenkov detectors as a cost-effective and ultra-fast alternative for future clinical range verification applications.