Development of a Real-Time Pixel Array-Type Detector for Ultrahigh Dose-Rate Beams.

Although research into ultrahigh dose-rate (UHDR) radiation therapy is ongoing, there is a significant lack of experimental measurements for two-dimensional (2D) dose-rate distributions. Additionally, conventional pixel-type detectors result in significant beam loss. In this study, we developed a pixel array-type detector with adjustable gaps and a data acquisition system to evaluate its effectiveness in measuring UHDR proton beams in real time. We measured a UHDR beam at the Korea Institute of Radiological and Medical Sciences using an MC-50 cyclotron, which produced a 45-MeV energy beam with a current range of 10-70 nA, to confirm the UHDR beam conditions. To minimize beam loss during measurement, we adjusted the gap and high voltage on the detector and determined the collection efficiency of the developed detector through Monte Carlo simulation and experimental measurements of the 2D dose-rate distribution. We also verified the accuracy of the real-time position measurement using the developed detector with a 226.29-MeV PBS beam at the National Cancer Center of the Republic of Korea. Our results indicate that, for a current of 70 nA with an energy beam of 45 MeV generated using the MC-50 cyclotron, the dose rate exceeded 300 Gy/s at the center of the beam, indicating UHDR conditions. Simulation and experimental measurements show that fixing the gap at 2 mm and the high voltage at 1000 V resulted in a less than 1% loss of collection efficiency when measuring UHDR beams. Furthermore, we achieved real-time measurements of the beam position with an accuracy of within 2% at five reference points. In conclusion, our study developed a beam monitoring system that can measure UHDR proton beams and confirmed the accuracy of the beam position and profile through real-time data transmission.

Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect.

Metallic nanoparticles (MNP) are able to release localized x-rays when activated with a high energy proton beam by the particle-induced x-ray emission (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based x-ray emission directed at CT26 tumor cells in vitro, when administered with either gold (average diameter 2 and 13 nm) or iron (average diameter 14 nm) nanoparticles (GNP or SNP), increased with MNP solution concentration over the range of 0.1-2 mg ml(-1). With irradiation by a 45 MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study in CT26 mouse tumor models with tumor regression assay demonstrated significant tumor dose enhancement, thought to be a result of the PIXE effect when compared to conventional PT without MNP (radiation-only group) using a 45 MeV proton beam (p < 0.02). Those receiving GNP or SNP injection doses of 300 mg kg(-1) body weight before proton beam therapy demonstrated 90% or 75% tumor volume reduction (TVR) in 20 days post-PT while the radiation-only group showed only 18% TVR and re-growth of tumor volume after 20 days. Higher complete tumor regression (CTR) was observed in 14-24 days after a single treatment of PT with an average rate of 33-65% for those receiving MNP compared with 25% for the radiation-only group. A lower bound of therapeutic effective MNP concentration range, in vivo, was estimated as 30-79 µg g(-1) tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread-out Bragg peak (SOBP) technique. The use of a combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone, may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases.

Determination of the dose-depth distribution of proton beam using resazurin assay in vitro and diode laser-induced fluorescence detection.

In this study the dose-depth distribution pattern of proton beams was investigated by inactivation of human cells exposed to high-LET (linear energy transfer) protons. The proton beams accelerated up to 45 MeV were horizontally extracted from the cyclotron, and were delivered to the cells acutely through a home made prototype over a range of physical depths (in the form of a variable water column). The biological systems used here were two in vitro cell lines, including human embryonic kidney cells (HEK 293), and human breast adenocarcinoma cell line (MCF-7). Cells were exposed to unmodulated proton beam radiation at a dose of 50 Gy similar to that used in therapy. Resazurin metabolism assay was investigated for measurement of cell response to irradiation as a simple and non-destructive assay. In the resazurin reduction test the non-fluorescent probe dye is reduced to pink and highly fluorescent resorufin. The dose-depth distribution of proton beam obtained based on the highly sensitive laser-induced fluorometric determination of resorufin was found to coincide well with the data collected using conventional film based dosimetry. The resazurin method yielded data comparable with the optical micrographs of the irradiated cells, showing the least cell survival at the measured Bragg-peak position of 10 mm. In addition, fused silica capillary was used as a sample container to increase the probability for irradiated laser beam to probe and excite resorufin in small sample volume of the capillary. The developed method has the potential to serve as a non-destructive, sample-thrifty, and time saving tool to realize more realistic, practical dose-depth distribution of proton beam compared to conventional in vitro cell viability assessment techniques.