Prompt gamma timing for range verification with carbon ion irradiation: first experimental measurements and comparison with Geant4 Monte Carlo simulations

Prompt Gamma Timing (PGT) is a promising technique for in vivo range verification in particle therapy, exploiting the time-of-flight between primary particles and prompt gamma rays emitted by nuclear interactions. PGT distribution is highly sensitive to beam energy and target density, which, under controlled detector positioning, enables real-time monitoring of particle range, detection of morphological changes, and support for adaptive treatment strategies. Objective: This study investigates for the first time the application of PGT in carbon ion therapy. Approach: Measurements were performed using a dedicated detection system composed of a silicon strip sensor for primary ion timing and a LaBr3(Ce) scintillator read out by a SiPM matrix for secondary radiation. Carbon ion beams with energies of 166.41, 268.86, and 398.84 MeV/u irradiated a homogeneous 30.0 cm PMMA target at CNAO (Pavia, Italy). The secondary radiation detector was positioned at four off-beam positions to assess the robustness of the PGT technique. Monte Carlo simulations based on Geant4 were conducted for all configurations to evaluate agreement and predictive capability. Main Results: A quantitative bin-by-bin comparison of experimental and simulated PGT intensities demonstrated strong agreement within the 95% confidence interval, with no incompatible bins at 166.41 MeV/u, at most 1% at 268.86 MeV/u, and up to 8% at 398.84 MeV/u, depending on detector position. Prompt gammas were identified as the dominant contribution to the detected signals, particularly for detector positions upstream with respect to the primary particle beam, minimizing signal contamination from neutrons and charged fragments. Significance: The validated experimental - simulation framework confirms the capability of the proposed PGT system to resolve energy-dependent differences and highlights its potential for detecting clinically relevant changes in the particle beam range, supporting further development toward real-time monitoring in carbon ion therapy.