Proton beam range verification using off-site PET by imaging novel proton-activated markers

Previously we showed that when ⁶⁸Zn and Cu markers are placed along the distal end of the proton beam range, they result in higher PET signals than surrounding material such as Plastic Water® and balsa wood following proton treatment. In this work we investigated the use of PET signals from activated ⁶⁸Zn and Cu markers for accurate proton range verification in two pseudo-clinical settings. ⁶⁸Zn (>97%) and natural Cu (⁶³Cu, 69% ; ⁶⁵Cu, 31%) markers (10 × 10 mm) of different thicknesses (0.1, 0.25, and 0.5 mm) were imbedded at 4 different distal fall-off depths in a balsa wood (simulating lung tissue) phantom. In a separate experiment, a rectangular block of raw beef (12 × 16 × 5 cm) simulating soft tissue was cut diagonally and imbedded with the same kind of ⁶⁸Zn and Cu markers. Both phantoms were CT scanned for treatment planning and irradiated by a 160 MeV, 10-cm SOBP proton beam with 5 Gy and scanned for 5 hrs using an off-site PET scanner. Images were reconstructed using a 30 min interval without decay correction and using various post-irradiation delays to determine the image with the best visibility of activated markers. Treatment planned isodose lines of the phantom were overlaid on top of marker locations to correlate the isodose line level to marker activation. The best visibility of a 30 min PET scan was obtained after 1 and 2 hr delays for balsa wood and beef phantoms, respectively. Marker visibility increased with marker volume and scan time post irradiation until 1 hr (for balsa) and 2 hrs (for beef) before it decreased due to a decrease in accumulated coincidence events. ⁶⁸Zn markers showed signals when located at > 50% isodose line irrespective of different post-irradiation delays. However, Cu markers show signals in balsa phantom (1 hr delay) when located at > 50% isodose line while in beef phantom (2 hrs delay) when located at > 95% isodose line. This is due to the proton energy (and depth) dependency of different progeny radioisotopes from activated Cu. Markers located beyond those isodose lines were not activated. In both cases, markers of > 25 mm³ were clearly visible. Activation of ⁶⁸Zn and Cu markers and their correspondence with isodose lines suggest the possibility of using implanted markers for proton range verification.