Characterization of proton-activated implantable markers for proton range verification using PET J. Cho1, G. Ibbott1, M. Kerr1, R. A. Amos2, F. Stingo1, and O. Mawlawi1 1 The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 University College London Hospitals NHS Foundation Trust, London, UK P207, PTCOG53: Shanghai, China. 2014 Background / Aim Conventional proton beam range verification using PET relies on tissue activation. This process however is affected by minimal activation near the end of the proton range, perfusion-driven activity washouts, and short half-lives of progeny radioisotopes, which requires an in-beam, in-room, or on-site PET scanner. While the installation of such a PET scanner can be financially and technically challenging for many proton centers, previous work (Cho et al Phys. Med. Biol. 58 7497-7512) showed that it was feasible to implant long-lived proton-activated fiducial markers for proton range verification using an off-site PET scanner. Here, we expand on that work by characterizing the relationships between marker volume, dose, and PET scan time in two tissue-like phantoms. The aim of this research was to determine the optimal marker volume to provide sufficient PET signal for several marker types, phantom materials, doses, and PET scan times. Results continues Results The visibility of activated markers increased in proportion to the marker volume, dose, and PET scan time for both phantoms. 60 and 120 min post-irradiation delays provided maximum marker SNR for balsa and beef phantoms, respectively. ± 2 mm depth variations were introduced for marker implantation from the maximum 68Zn and Cu activation depth (108 mm). 108 ± 2 mm (= 106, 110 mm) are the region of > 80% of maximum 68Zn activation. This variation in depths was adapted for practical consideration since it is very difficult to implant markers at exact depth in real clinical situation. The following figure shows no practical difference in visibility scores for 50 mm3 Cu markers embedded at two different depths. (a) (a) (b) (b) Methods & Materials Fig. 2: PET/CT fusion images of the balsa wood phantom in fig 1. (a) Beam’s eye view of the activated markers on the plane at depth 3 (108 mm/99%). (b) Lateral view on the plane of the 50 mm3 Cu markers. Two phantoms were made; one using low-density balsa wood (~ 0.1 g/cm3) as a lung substitute and a second using beef (~ 1.0 g/cm3) as a soft-tissue substitute. Markers made of two materials (Cu and 68Zn) and having three different volumes (10, 20, and 50 mm3) were embedded in each phantom. The phantoms and markers were irradiated with 160 MeV protons to four doses (1, 2, 3, and 5 Gy). The markers were located in the distal dose fall-off region, because a previous study showed the maximum activation occurred at this depth. After irradiation, the phantoms were moved to an off-site PET scanner and scanned in list-mode. Data were acquired with 20-, 30-, and 40-min scan times following several different delay times (30, 45, 60, 75, 90, 105, 120, 135, and 150 min) to investigate the maximum SNR. Reconstructed PET/CT images were then scored for marker visibility on a 5 point scale by 13 radiologists. We used a linear model, with marker visibility scores as the response variable and all other factors (marker type, marker volume, phantom material, dose, and PET scan time) as covariates to understand how marker volume affects the visibility score. (b) Fig. 5: Visibility score comparison of two 50 mm3 Cu markers embedded at two different depths and irradiated by 1 Gy. (a) Cu marker was embedded at a depth of 106 mm and the average visibility score was 4.2. (b) Cu marker was embedded at a depth of 110 mm and the average visibility score was 4.0. The marker volumes that provided a visibility score of 3 (moderately visible) were determined for both phantoms, several dose levels and all PET scan times. The phantom material was found to have very little influence on the marker volume required (average difference and standard deviation were 1.5 % and 1.4 %, respectively). (a)  Required marker volume (mm3) - Cu markers in low density balsa  PET scan time (min) Dose (Gy) 1 2 3 4 5 20 55 49 43 36 30 52 46 39 33 27 40 24 (b) Fig. 3: PET/CT fusion images of beef phantom of similar setup as fig 1. (a) Beam’s eye view on the plane at depth 2 (105 mm/100%). (b) Lateral view on the plane of the 50 mm3 Cu marker.  Required marker volume (mm3) - Cu markers in beef phantom  PET scan time (min) Dose (Gy) 1 2 3 4 5 20 55 48 42 36 30 52 45 39 33 27 40 49 24  Required marker volume (mm3) - 68Zn markers in low density balsa  PET scan time (min) Dose (Gy) 1 2 3 4 5 20 35 29 23 17 10 30 32 26 14 7 40 11 (a) (b) Tab. 1: The required volume of markers to provide a visibility score of 3. Conclusion (b) The visibility and marker volume information obtained in this study can be used as a guideline in planning preclinical studies using anthropomorphic phantoms or animals, with a long-term goal of optimizing such markers for clinical use. Fig. 4: Variation of average visibility scores with marker volume and dose for different marker materials, embedding phantom materials and PET scan times. The mesh grid is a linear interpolation of the measurement points (solid spheres). Fig. 1: (a) Proton irradiation setup for Cu and 68Zn markers embedded in a balsa wood phantom. (b) Locations of markers overlaid on the percentage depth dose (PDD) curve of the proton beam.