In vivo dose delivery verification in proton therapy can be performed by positron emission tomography (PET) of the positron-emitting nuclei produced by the proton beam in the patient. A PET scanner installed in the treatment position of a proton therapy facility that takes data with the beam on will see very short-lived nuclides as well as longer-lived nuclides. The most important short-lived nuclide for proton therapy is N (Dendooven et al 2015 Phys. Med. Biol. 60 8923-47), which has a half-life of 11 ms. The results of a proof-of-principle experiment of beam-on PET imaging of short-livedN nuclei are presented. The Philips Digital Photon Counting Module TEK PET system was used, which is based on LYSO scintillators mounted on digital SiPM photosensors. A 90 MeV proton beam from the cyclotron at KVI-CART was used to investigate the energy and time spectra of PET coincidences during beam-on. Events coinciding with proton bunches, such as prompt gamma rays, were removed from the data via an anti-coincidence filter with the cyclotron RF. The resulting energy spectrum allowed good identification of the 511 keV PET counts during beam-on. A method was developed to subtract the long-lived background from the N image by introducing a beam-off period into the cyclotron beam time structure. We measured 2D images and 1D profiles of theN distribution. A range shift of 5 mm was measured as 6  ±  3 mm using the N profile. A larger, more efficient, PET system with a higher data throughput capability will allow beam-onN PET imaging of single spots in the distal layer of an irradiation with an increased signal-to-background ratio and thus better accuracy. A simulation shows that a large dual panel scanner, which images a single spot directly after it is delivered, can measure a 5 mm range shift with millimeter accuracy: 5.5  ±  1.1 mm for 1  ×  10 protons and 5.2  ±  0.5 mm for 5  ×  10 protons. This makes fast and accurate feedback on the dose delivery during treatment possible.

The only method for in vivo dose delivery verification in proton beam radiotherapy in clinical use today is positron emission tomography (PET) of the positron emitters produced in the patient during irradiation. PET imaging while the beam is on (so called beam-on PET) is an attractive option, providing the largest number of counts, the least biological washout and the fastest feedback. In this implementation, all nuclides, independent of their half-life, will contribute. As a first step towards assessing the relevance of short-lived nuclides (half-life shorter than that of (10)C, T1/2  =  19 s) for in vivo dose delivery verification using beam-on PET, we measured their production in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: (12)N (T1/2  =  11 ms) on carbon (9% of (11)C), (29)P (T1/2  =  4.1 s) on phosphorus (20% of (30)P) and (38m)K (T1/2  =  0.92 s) on calcium (113% of (38g)K). No short-lived nuclides are produced on oxygen. The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, (12)N dominates up to 70 s. On bone tissue, (12)N dominates over (15)O during the first 8-15 s (depending on carbon-to-oxygen ratio). The short-lived nuclides created on phosphorus and calcium provide 2.5 times more beam-on PET counts than the long-lived ones produced on these elements during a 70 s irradiation. From the estimated number of (12)N PET counts, we conclude that, for any tissue, (12)N PET imaging potentially provides equal to superior proton range information compared to prompt gamma imaging with an optimized knife-edge slit camera. The practical implementation of (12)N PET imaging is discussed.

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