Most of the work in the first stages of CAPPERAM was devoted to developing a calculation tool for activation of contrast agents. This was implemented using TOPAS Monte Carlo framework and a careful evaluation of existing proton-reaction cross sections. The calculation tool was validated against phantom measurements using water enriched with 18-O (18W) as a contrast agent. These measurements were carried out at the WPE center in Essen (España et al 2020a, see Figure 1). Some of the cross-sections required for an accurate prediction of the induced activity were not readily available in the literature; therefore, with the help of colleagues at the Nuclear Physics Group at UCM, we implemented an online setup for measuring activation cross sections and used it at a number of experimental campaigns at CMAM (Espinosa et al, 2020) and WPE.
Finally, promising results using 18-W as contrast agent allowed us to perform an end-to-end proof-of-concept study using chick embryos as an animal model (Figure 2). Tumors grown at the chorioallantoic membrane (CAM) of chick embryos were infused with 18-W and irradiated with low-energy proton beams. Shortly after irradiation, dynamic PET images were acquired using a SuperArgus PET/CT scanner at Sedecal Molecular Imaging (see Figure 3), which allowed a submillimetric localization of the irradiated volume.
Main scientific results:
- W-18 was identified as most promising contrast agent for proton radiotherapy thanks to its simplicity of use, high-concentrations achievable in tissue and range neutrality. Other candidates, such as Zn nanoparticles or iodine, remain under study.
- A dose-activity calculation algorithm was implemented and validated against experimental measurements (España et al 2020, Rad.Phys.Chem in press).
- Cross-section measurements for Zn and I targets were performed, including the first reported set of experimental data for the 127I(p,n)127mXe reaction (Espinosa et al 2020, Rad.Phys.Chem under review).
- As a final proof-of-concept testing all stages of the project, 18-W was used to image dose-maps delivered to tumors grown at the CAM of chick embryos, using a preclinical PET scanner (España et al 2020, Med. Phys, under review).
- Reported advances in electronics (Sánchez-Tembleque et al 2019) and collaboration in joint projects has allowed for measurements at the Quironsalud proton therapy center (Mazal 2020, Front. Oncol).
