Direct proton range verification using oxygen-18 enriched water as a contrast agent

Espana et al.

In this paper by España et al., the MOLECUBES β-CUBE and X-CUBE was used to investigate whether oxygen-18 enriched water could potentially be used as an in vivo biomarker to verify proton beam therapy delivery .

Research question

The researcher propose the use of 18O-enriched water as a suitable contrast agent for potential in-vivo range verification in proton therapy. The low energy production threshold of 18F (2.6 MeV, proton range in water of 115 μm) leads to tissue activation in very close proximity to the maximum dose deposition, facilitating accurate range verification with off-line PET imaging.


This idea has been explored in a phantom experiment. A 3D-printed phantom containing inserts with 18O- enriched water was irradiated with a 100-MeV, 8 × 8 cm2 proton beam, and the induced activity was measured with a small-animal PET-CT 30 min after irradiation. The images obtained were compared against Monte Carlo simulation using TOPAS.


Good agreement was observed between reconstructed and simulated activity profiles (within 40% for specific 18F activity), with excellent spatial match to the simulated dose deposition. Because of the long half-life of 18F, the specific activity of the contrast agent could be separated and was clearly observed for more than 2 h after irradiation. Activity distribution maps were used to determine the position of the Bragg peak within 2 mm for three different regions of interest. These results show the potential of 18O-enriched water as a contrast agent in proton therapy.