Mapping ¹⁵O production rate for proton therapy verification

Purpose This work was a proof-of-principle study for the evaluation of oxygen-15 (¹⁵O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. Methods and Materials Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of ¹⁵O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. Results PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of ¹⁵O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using ¹⁵O decay constant, whereas the live thigh activity decayed faster. Most importantly, the ¹⁵O production rates agreed within 2% (P>.5) between conditions. Conclusions We developed a new method for quantitative measurement of ¹⁵O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of ¹⁵O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, ¹⁵O clearance rates may be useful in monitoring permeability changes due to therapy.