We 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.

我们建议使用富含¹⁸ O的水作为合适的造影剂，用于质子治疗中潜在的体内范围验证。¹⁸ F（2.6 MeV，115 mg的水中质子范围）的低能量产生阈值导致非常接近最大剂量沉积的组织活化，从而促进了离线PET成像的精确范围验证。

这个想法已经在幻像实验中进行了探索。用100MeV，8×8 cm ^2的质子束辐照3D打印的包含¹⁸ O富集水的插入物的幻像，并在辐照30分钟后用小动物PET-CT测量诱导的活性。将获得的图像与使用TOPAS的蒙特卡洛模拟进行了比较。

在重建的和模拟的活性曲线之间观察到良好的一致性（对于特定的¹⁸ F活性，误差在40％以内），与模拟的剂量沉积具有极好的空间匹配。由于¹⁸ F的半衰期较长，因此可以分离出造影剂的比活性，并且在照射后超过2小时清晰可见。活性分布图用于确定三个不同感兴趣区域在2毫米内的布拉格峰位置。这些结果表明富含¹⁸ O的水在质子治疗中作为造影剂的潜力。