Feasibility of proton-activated implantable markers for proton range verification using PET

Proton beam range verification using positron emission tomography (PET) currently relies on proton activation of tissue, the products of which decay with a short half-life and necessitate an on-site PET scanner. Tissue activation is, however, negligible near the distal dose fall-off region of the proton beam range due to their high interaction energy thresholds. Therefore Monte Carlo simulation is often supplemented for comparison with measurement; however, this also may be associated with systematic and statistical uncertainties. Therefore, we sought to test the feasibility of using long-lived proton-activated external materials that are inserted or infused into the target volume for more accurate proton beam range verification that could be performed at an off-site PET scanner. We irradiated samples of ≥98% ¹⁸O-enriched water, natural Cu foils, and >97% ⁶⁸Zn-enriched foils as candidate materials, along with samples of tissue-equivalent materials including ¹⁶O water, heptane (C₇H₁₆), and polycarbonate (C ₁₆H₁₄O₃)_n, at four depths (ranging from 100% to 3% of center of modulation (COM) dose) along the distal fall-off of a modulated 160 MeV proton beam. Samples were irradiated either directly or after being embedded in Plastic Water® or balsa wood. We then measured the activity of the samples using PET imaging for 20 or 30 min after various delay times. Measured activities of candidate materials were up to 100 times greater than those of the tissue-equivalent materials at the four distal dose fall-off depths. The differences between candidate materials and tissue-equivalent materials became more apparent after longer delays between irradiation and PET imaging, due to the longer half-lives of the candidate materials. Furthermore, the activation of the candidate materials closely mimicked the distal dose fall-off with offsets of 1 to 2 mm. Also, signals from the foils were clearly visible compared to the background from the activated Plastic Water® and balsa wood phantoms. These results indicate that markers made from these candidate materials could be used for in vivo proton range verification using an off-site PET scanner.