Proton FLASH effects on mouse skin at different oxygen tensions.

Objective. Irradiation at FLASH dose rates (>40 Gy s-1) has received great attention due to its reported normal tissue sparing effect. The FLASH effect was originally observed in electron irradiations but has since been shown to also occur with both photon and proton beams. Several mechanisms have been proposed to explain the tissue sparing at high dose rates, including effects involving oxygen, such as depletion of oxygen within the irradiated cells. In this study, we investigated the protective role of FLASH proton irradiation on the skin when varying the oxygen concentration.Approach. Our double scattering proton system provided a 1.2 × 1.6 cm2elliptical field at a dose rate of ∼130 Gy s-1. The conventional dose rate was ∼0.4 Gy s-1. The legs of the FVB/N mice were marked with two tattooed dots and fixed in a holder for exposure. To alter the skin oxygen concentration, the mice were breathing pure oxygen or had their legs tied to restrict blood flow. The distance between the two dots was measured to analyze skin contraction over time.Main results. FLASH irradiation mitigated skin contraction by 15% compared to conventional dose rate irradiation. The epidermis thickness and collagen deposition at 75 d following 25 to 30 Gy exposure suggested a long-term protective function in the skin from FLASH irradiation. Providing the mice with oxygen or reducing the skin oxygen concentration removed the dose-rate-dependent difference in response.Significance. FLASH proton irradiation decreased skin contraction, epidermis thickness and collagen deposition compared to standard dose rate irradiations. The observed oxygen-dependence of the FLASH effect is consistent with, but not conclusive of, fast oxygen depletion during the exposure.

Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.

Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect. A 16 × 12 mm2 elliptical field with a dose rate of ~120 Gy/s was provided by a 228 MeV proton pencil beam. Partial abdominal irradiation was delivered to C57BL/6j and immunodeficient Rag1-/-/C57 mice. Proliferating crypt cells were counted at 2 days post exposure, and the thickness of the muscularis externa was measured at 280 days following irradiation. FLASH irradiation did not reduce the morbidity or mortality of conventional irradiation in either strain of mice; in fact, a tendency for worse survival in FLASH-irradiated mice was observed. There were no significant differences in lymphocyte numbers between FLASH and conventional-dose-rate mice. A similar number of proliferating crypt cells and a similar thickness of the muscularis externa following FLASH and conventional dose rate irradiation were observed. Partial abdominal FLASH proton irradiation at 120 Gy/s did not spare normal intestinal tissue, and no difference in lymphocyte depletion was observed. This study suggests that the effect of FLASH irradiation may depend on multiple factors, and in some cases dose rates of over 100 Gy/s do not induce a FLASH effect and can even result in worse outcomes.

Al2O3:C optically stimulated luminescence dosimeters (OSLDs) for ultra-high dose rate proton dosimetry.

The response of Al2O3:C optically stimulated luminescence detectors (OSLDs) was investigated in a 250 MeV pencil proton beam. The OSLD response was mapped for a wide range of average dose rates up to 9000 Gy s-1, corresponding to a ∼150 kGy s-1instantaneous dose rate in each pulse. Two setups for ultra-high dose rate (FLASH) experiments are presented, which enable OSLDs or biological samples to be irradiated in either water-filled vials or cylinders. The OSLDs were found to be dose rate independent for all dose rates, with an average deviation <1% relative to the nominal dose for average dose rates of (1-1000) Gy s-1when irradiated in the two setups. A third setup for irradiations in a 9000 Gy s-1pencil beam is presented, where OSLDs are distributed in a 3 × 4 grid. Calculations of the signal averaging of the beam over the OSLDs were in agreement with the measured response at 9000 Gy s-1. Furthermore, a new method was presented to extract the beam spot size of narrow pencil beams, which is in agreement within a standard deviation with results derived from radiochromic films. The Al2O3:C OSLDs were found applicable to support radiobiological experiments in proton beams at ultra-high dose rates.

Measurement of 43Sc and 44Sc production cross-section with an 18MeV medical PET cyclotron.

43Sc and 44Sc are positron emitter radionuclides that, in conjunction with the ß- emitter 47Sc, represent one of the most promising possibilities for theranostics in nuclear medicine. Their availability in suitable quantity and quality for medical applications is an open issue and their production with medical cyclotrons represents a scientific and technological challenge. For this purpose, an accurate knowledge of the production cross sections is mandatory. In this paper, we report on the cross section measurement of the reactions 43Ca(p,n)43Sc, 44Ca(p,2n) 43Sc, 46Ti(p,α)43Sc, and 44Ca(p,n)44Sc at the Bern University Hospital cyclotron. A study of the production yield and purity performed by using commercially available enriched target materials is also presented.