The radiosensitizing effect of platinum nanoparticles in proton irradiations is not caused by an enhanced proton energy deposition at the macroscopic scale.

Objective.Due to the radiosensitizing effect of biocompatible noble metal nanoparticles (NPs), their administration is considered to potentially increase tumor control in radiotherapy. The underlying physical, chemical and biological mechanisms of the NPs' radiosensitivity especially when interacting with proton radiation is not conclusive. In the following work, the energy deposition of protons in matter containing platinum nanoparticles (PtNPs) is experimentally investigated.Approach.Surfactant-free monomodal PtNPs with a mean diameter of (40 ± 10) nm and a concentration of 300 µg ml-1, demonstrably leading to a substantial production of reactive oxygen species (ROS), were homogeneously dispersed into cubic gelatin samples serving as tissue-like phantoms. Gelatin samples without PtNPs were used as control. The samples' dimensions and contrast of the PtNPs were verified in a clinical computed tomography scanner. Fields from a clinical proton machine were used for depth dose and stopping power measurements downstream of both samples types. These experiments were performed with a variety of detectors at a pencil beam scanning beam line as well as a passive beam line with proton energies from about 56-200 MeV.Main results.The samples' water equivalent ratios in terms of proton stopping as well as the mean proton energy deposition downstream of the samples with ROS-producing PtNPs compared to the samples without PtNPs showed no differences within the experimental uncertainties of about 2%.Significance.This study serves as experimental proof that the radiosensitizing effect of biocompatible PtNPs is not due to a macroscopically increased proton energy deposition, but is more likely caused by a catalytic effect of the PtNPs. Thus, these experiments provide a contribution to the highly discussed radiobiological question of the proton therapy efficiency with noble metal NPs and facilitate initial evidence that the dose calculation in treatment planning is straightforward and not affected by the presence of sensitizing PtNPs.

Can a ToF-PET photon attenuation reconstruction test stopping-power estimations in proton therapy? A phantom study.

Objective. The aim of the phantom study was to validate and to improve the computed tomography (CT) images used for the dose computation in proton therapy. It was tested, if the joint reconstruction of activity and attenuation images of time-of-flight PET (ToF-PET) scans could improve the estimation of the proton stopping-power.Approach. The attenuation images, i.e. CT images with 511 keV gamma-rays (γCTs), were jointly reconstructed with activity maps from ToF-PET scans. Theß+activity was produced with FDG and in a separate experiment with proton-induced radioactivation. The phantoms contained slabs of tissue substitutes. The use of theγCTs for the prediction of the beam stopping in proton therapy was based on a linear relationship between theγ-ray attenuation, the electron density, and the stopping-power of fast protons.Main results. The FDG based experiment showed sufficient linearity to detect a bias of bony tissue in the heuristic look-up table, which maps between x-ray CT images and proton stopping-power.γCTs can be used for dose computation, if the electron density of one type of tissue is provided as a scaling factor. A possible limitation is imposed by the spatial resolution, which is inferior by a factor of 2.5 compared to the one of the x-ray CT.γCTs can also be derived from off-line, ToF-PET scans subsequent to the application of a proton field with a hypofractionated dose level.Significance. γCTs are a viable tool to support the estimation of proton stopping with radiotracer-based ToF-PET data from diagnosis or staging. This could be of higher potential relevance in MRI-guided proton therapy.γCTs could form an alternative approach to make use of in-beam or off-line PET scans of proton-inducedß+activity with possible clinical limitations due to the low number of coincidence counts.