Feasibility of quasi-prompt PET-based range verification in proton therapy

Compared to photon therapy, proton therapy allows a better conformation of the dose to the tumor volume with reduced radiation dose to co-irradiated tissues. In vivo verification techniques including positron emission tomography (PET) have been proposed as quality assurance tools to mitigate proton range uncertainties. Detection of differences between planned and actual dose delivery on a short timescale provides a fast trigger for corrective actions. Conventional PET-based imaging of ¹⁵O (T_1/2 = 2 min) and ¹¹C (T_1/2 = 20 min) distributions precludes such immediate feedback. We here present a demonstration of near real-time range verification by means of PET imaging of ¹²N (T_1/2 = 11 ms). PMMA and graphite targets were irradiated with a 150 MeV proton pencil beam consisting of a series of pulses of 10 ms beam-on and 90 ms beam-off. Two modules of a modified Siemens Biograph mCT PET scanner (21 × 21 cm² each), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. The modifications enable the detectors to be switched off during the beam-on periods. ¹²N images were reconstructed using planar tomography. Using a 1D projection of the 2D reconstructed ¹²N image, the activity range was obtained from a fit of the activity profile with a sigmoid function. Range shifts due to modified target configurations were assessed for multiples of the clinically relevant 10⁸ protons per pulse (approximately equal to the highest intensity spots in the pencil beam scanning delivery of a dose of 1 Gy over a cubic 1 l volume). The standard deviation of the activity range, determined from 30 datasets obtained from three irradiations on PMMA and graphite targets, was found to be 2.5 and 2.6 mm (1σ) with 10⁸ protons per pulse and 0.9 and 0.8 mm (1σ) with 10⁹ protons per pulse. Analytical extrapolation of the results from this study shows that using a scanner with a solid angle coverage of 57%, with optimized detector switching and spot delivery times much smaller than the ¹²N half-life, an activity range measurement precision of 2.0 mm (1σ) and 1.3 mm (1σ) within 50 ms into an irradiation with 4 × 10⁷ and 10⁸ protons per pencil beam spot can be potentially realized. Aggregated imaging of neighboring spots or, if possible, increasing the number of protons for a few probe beam spots will enable the realization of higher precision range measurement.