Gold nanoparticles for tumor detection with proton radiography: optimizing sensitivity and determining detection limits

Proton radiography is a promising imaging technique that can be used to improve the treatment plan quality for proton therapy, by providing accurate estimates of proton stopping power. While a proton radiograph has accurate information about proton stopping power, it also has an inherently low tissue contrast for diagnostic purposes, as compared to X-ray imaging. The nature of energetic, massive protons as a radiographic probe is that they require a high-Z tracer to provide sufficient proton scatter in order to delineate target structures. Gold nanoparticles could be that ideal tracer due to a Z = 79, and their biocompatibility. Here the detection thresholds for gold-nanoparticle targeted tumors are evaluated using instantaneous, 800-MeV proton radiography, at the Los Alamos Neutron Science Center. Data is compared against MRI data in pre-clinical mouse models with 4T1 tumors directly injected with gold nanoparticle solution. The proton radiography system is then optimized using novel collimation schemes, including a dark field proton radiographic setup, that aimed to increase sensitivity and reduce dose. Results evaluated here are extrapolated to 211-MeV proton radiographic energy, to compare against expectations at clinical treatment energies. At that lower energy, proton radiography is more sensitive to the multiple Coulomb scattering introduced by a high-Z tracer.