PURPOSE:Radiation‑induced musculoskeletal toxicities are one of the major limitations in pediatric patients whose skeletons are still developing. FLASH radiation therapy, delivered at ultrahigh dose rates (>40 Gy/s), has demonstrated normal-tissue sparing in preclinical models, but its effects on the developing skeleton and marrow remain incompletely characterized. This study evaluated the normal-tissue effects 10 weeks after proton FLASH irradiation in juvenile mice, modeling the pediatric context. METHODS AND MATERIALS:Juvenile C57BL/6 mice (3 to 4 weeks old) were randomized to receive 11 Gy protons with FLASH (≈200 Gy/s), conventional dose-rate irradiation (CONV, 0.2 Gy/s average), or sham treatment (SHAM) to the left hind leg using a synchrotron-based proton beamline. Mice were followed for 10 weeks posttreatment. Bone toxicity was assessed with micro-computed tomography, including bone mineral density, bone volume fraction, trabecular indices, and limb length. Bone marrow cellularity was quantified on hematoxylin and eosin-stained sections, and muscle fibrosis was assessed using Masson's trichrome staining. RESULTS:Proton FLASH irradiation preserved bone microarchitecture compared with conventional irradiation, with higher bone mineral density and bone volume fractions (P < .05). Trabecular number was maintained, while the structure model index indicated a mechanically favorable trabecular structure in the FLASH group. Proton FLASH also partially preserved longitudinal bone growth, with tibial length ratios of 0.94 (FLASH) versus 0.91 (CONV) versus 1.00 (SHAM). Bone marrow cellularity was preserved in FLASH mice (5.3% reduction vs SHAM) compared with CONV (11.3% reduction; P < .05). Muscle fibrosis was significantly lower in the FLASH group (fibrosis positivity 2.6% vs 3.0% for FLASH vs CONV; P < .05). No severe immobility or weight loss was observed across groups. CONCLUSIONS:Proton FLASH reduced musculoskeletal and marrow toxicities at 10 weeks postirradiation in juvenile mice. These findings extend prior proton FLASH adult mice studies by demonstrating tissue sparing in a juvenile model and support further investigation of FLASH as a strategy to reduce normal‑tissue injury during radiation therapy of pediatric patients.

Modern photon-based, intensity-modulated radiation therapy (IMRT) kills tumors but may also excessively damage normal tissues; the resultant morbidity can prompt treatment interruptions, worsen tumor control, and degrade quality of life. Charged particles (eg, protons, carbon ions) may be less toxic and more effective than IMRT because particles irradiate less surrounding normal tissues and are more biologically effective than IMRT. However, protons/carbon ions have physical drawbacks that can affect dose precision. Helium ions are being explored as an alternative type of charged-particle therapy because their biophysical characteristics are intermediate between those of protons and carbon ions, potentially improving treatment precision. However, systematic studies of helium ion radiotherapy (HeRT) are scarce. We review current knowledge of the biophysical effects of HeRT: its relative biological effectiveness (RBE) versus photons; its effects on gene mutation, DNA damage and repair, cell cycling, cell death, and radiosensitization; and early explorations of ultra-high dose rate HeRT.

Accurate dosimetry is critical for safe and effective radiotherapy, yet no clinical method currently measures dose directly within the patient in vivo. Radiacoustic imaging (RAI), which detects acoustic waves generated by thermoelastic expansion during radiation delivery, offers a promising solution but has been limited to qualitative output. We present a quantitative RAI (qRAI) framework powered by a physics-informed neural network (PINN) that reconstructs quantitative dose maps in vivo. The PINN incorporates the physics of acoustic wave generation and propagation, along with a digital twin of the radiation delivery and radiacoustic detection systems, enabling accurate reconstruction from limited-view data. Reconstructed pressure maps are calibrated against experimental and simulated dose references. We validate the method across diverse clinical scenarios, including water tank dosimetry, human torso phantoms, and FLASH electron therapy. Compared to purely data-driven models, our PINN approach offers superior robustness and generalizability, especially in clinical settings lacking experimental ground truth. These results establish PINN-based qRAI as a powerful tool for real-time, adaptive, and quantitative in vivo dosimetry.

Modern photon-based, intensity-modulated radiation therapy (IMRT) kills tumors but may also excessively damage normal tissues; the resultant morbidity can prompt treatment interruptions, worsen tumor control, and degrade quality of life. Charged particles (eg, protons, carbon ions) may be less toxic and more effective than IMRT because particles irradiate less surrounding normal tissues and are more biologically effective than IMRT. However, protons/carbon ions have physical drawbacks that can affect dose precision. Helium ions are being explored as an alternative type of charged-particle therapy because their biophysical characteristics are intermediate between those of protons and carbon ions, potentially improving treatment precision. However, systematic studies of helium ion radiotherapy (HeRT) are scarce. We review current knowledge of the biophysical effects of HeRT: its relative biological effectiveness (RBE) versus photons; its effects on gene mutation, DNA damage and repair, cell cycling, cell death, and radiosensitization; and early explorations of ultra-high dose rate HeRT.

Background:Clinical linear accelerators are an accessible platform for preclinical research on the biological effects of ultra-rapid electron irradiation (FLASH). However, they are not inherently designed for the accurate pulse control required for experiments using a small number of relatively high-dose pulses, and available methods for beam control such as respiratory gating can be error-prone owing to system latency. Purpose:Here we experimentally characterize the temporal latency of the respiratory gating system for controlling beam-on and beam-off at the individual linac pulse level. We use this information to develop accurate pulse delivery methods for preclinical FLASH research. Methods and Materials:We used programmable controller boards and a relay circuit to monitor and control delivery of specific numbers of pulses through the built-in monitor chamber and respiratory gating system of a Varian Trilogy linac. We modeled system response latency as a normally distributed random variable and experimentally recorded the probability of successful pulse delivery and inhibition relative to the time of beam-on and beam-off request signals to derive the mean and standard deviation of latency times at different pulse repetition frequencies. We implemented two methods - an adaptive method using only the delivered-pulse signal, and a synchronization method additionally using the linac's internal pulse-timing signal - and characterized their performance for standard and customized pulse sequences. Results:The mean and standard deviation values of the respiratory gating latency at 60, 90 and 180 Hz pulse repetition frequency were respectively 2.0±0.8 ms, 2.1±2.8 ms, and 2.4±1.9 ms for beam-on and 1.3±0.9 ms, 1.9±2.9 ms, and 1.8±2.1 ms for beam-off. Beam-on and beam-off latencies were similar to each other, and similar across pulse repetition frequencies. Characterizing the latency parameters permitted choosing optimal timing parameters that maximized the rate of successfully delivering the desired number of pulses using both adaptive and synchronization methods, exceeding 99% at 90 Hz for both methods, and reaching 95% (adaptive) and 80% (synchronization) at 180 Hz. This also enabled successful implementation of custom pulse sequences not natively available on the system. Conclusions:We demonstrated that accounting for latency and/or using the ability to read the prior information on expected pulse timing can provide high accuracy in delivering specified numbers of pulses. This reliability is critical for accurate dose delivery in preclinical FLASH research of single fraction and especially fractionated dosing regimens. The ability to generate custom pulse sequences enables more detailed exploration of the temporal dependence of biological FLASH effects.

ABSTRACT Triple negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Conventional treatments include neoadjuvant chemo-immunotherapy followed by surgical resection and may include further adjuvant immunotherapy and/or radiotherapy of the tumor bed and lymph nodes. Nonetheless, TNBC patients with residual disease have rapid metastatic recurrence. While the roles of metabolic and mitochondrial adaptations in chemotherapeutic resistance have been the subject of many studies, their importance in the context of ionizing radiation (IR) therapy remains poorly understood. We established longitudinal in vitro models of post-IR human TNBC, characterized by cellular regression to a residual phenotypic state, then eventual cell repopulation. This was accompanied by plastic adoption of unique metabolic, proteomic, and morphologic features that largely reverted when cells regrew. Following IR, residual cells exhibited extensive mitochondrial rewiring, including elevated mitochondrial content, oxidative phosphorylation (oxphos) rates, cristae structures, and metabolite levels. Concomitantly, levels of the short protein isoform of the mitochondrial inner membrane protein optic atrophy 1 (OPA1) were significantly elevated in residual cells, and OPA1 knockout ablated mitochondrial adaptations induced by IR. OPA1 genetic or pharmacologic perturbations led to improved cellular responses to IR. Metabolomic and proteomic analyses of radio-residual cells uncovered a coordinated program of antioxidant and redox capacity elevation with mitochondrial metabolism, which was corroborated by analyses of external datasets. Together, these findings provide evidence that TNBC cells surviving radiotherapy adopt an OPA1-dependent program of mitochondrial reorganization that supports their survival and regrowth, thereby positioning OPA1 as a therapeutic dependency that could improve radiotherapy efficacy in TNBC.

Objective.The main goal of this research is to verify the spatial fidelity of radiacoustic imaging (RAI) as a quantitative dosimetric monitoring tool for FLASH radiotherapy (FLASH-RT)in vivo. FLASH-RT delivers therapeutic radiation at ultra-high instantaneous dose rates (>106Gy s-1), offering substantial reductions in normal tissue toxicity while maintaining tumor control. However, clinical translation remains limited by the absence of real-time,in vivodosimetry systems capable of resolving dose delivery at microsecond timescales.Approach.Here, we present an RAI platform that enables volumetric, single-pulse mapping of radiation dose deposition during FLASH-RTin vivo. The system utilizes a 16 × 16 ultrasound transducer matrix array with a model-based reconstruction algorithm to generate quantitative, three-dimensional dose maps with single pulse-level temporal resolution.Main results.In both water phantoms andin vivomurine models, RAI demonstrates high concordance with film dosimetry and TOPAS Monte Carlo simulations (3%/3 mm gamma index pass rates greater than 90% for small fields).Significance.This work establishes RAI as a viable technology for real-time, quantitative electron FLASH dosimetryin vivofor the first time, with the potential to support adaptive delivery, improve treatment safety, and facilitate the clinical translation of FLASH-RT.

Abstract Introduction: Glioblastoma is a lethal brain tumor with poor response to current therapies, which include surgery, chemotherapy, and conventional radiation therapy (CONV-RT). Although, CONV-RT (0.01Gy/second) to brain tumors stimulate tumor antigen release, it also recruits immunosuppressive myeloid-derived suppressor cells and is associated with neurotoxicity. Ultrahigh-dose-rate or FLASH-RT, which delivers CONV-RT doses over a significantly shorter period (more than 40Gy/second) maintains tumor control, reduces normal tissue injury and is less immunosuppressive compared to CONV-RT across multiple cancer types. In our study, we compared the effects of FLASH-RT to CONV RT in syngeneic mouse GL261 glioblastoma-bearing mice. We hypothesized that FLASH-RT would be equally or more effective than CONV-RT for tumor control and result in less immunosuppression within the tumor and systemically. Methods: We stereotactically implanted 2 × 105 mouse GL261 cells into the right forebrain of C57BL/6 mice. Five days after tumor initiation, tumor bearing mice were treated with Sham-RT (control), CONV-RT (mean dose rate > 0.373 Gy/s), or FLASH-RT (mean dose rate >3.6x106 Gy/s). Brain tumor tissue and peripheral blood were collected on days 5 and 12 after treatment. To assess for changes in the tumor microenvironment after CONV-RT or FLASH-RT, we performed 10x Xenium spatial transcriptomics analysis (stRNA-seq; brain tumor, n = 6 mice per group), Lunaphore COMET multiplexed immunofluorescence assay (brain tumor, n = 6 mice per group), and flow cytometry (peripheral mononuclear cells, n = 6 mice per group). We also evaluated survival outcomes following treatment (n = 8 mice per group). Results: FLASH-RT significantly improved overall survival rate of GL261 bearing mice compared to CONV-RT (P <0.05) and Sham-RT (P < 0.001). FLASH-RT treatment markedly increased intratumoral CD8+ T-cell infiltration compared with CONV-RT (P <0.01) and Sham-RT (P < 0.01). We also found that compared to FLASH-RT, CONV-RT caused a significant decrease in circulating PD-1+CD8+ T-cells (P < 0.01), a potent antigen reactive cytotoxic T-cell population previously identified in human patients with glioblastoma. Conclusion: FLASH-RT is associated with better tumor control in mouse GL261 glioblastoma, increased intratumoral CD8+ T-cell infiltration, and preserves circulating antigen reactive PD1+CD8+ T-cells. These results indicate that FLASH-RT may synergize better with immune checkpoint inhibitors to re-invigorate anti-tumor T-cell responses against glioblastoma. Citation Format: Yanxia Ma, Nhat Nguyen, Xuehong Gui, Edgardo Aguilar, Luke Connell, Denae Neill, Emil Schüler, Chibawanye I. Ene. FLASH radiotherapy improves survival in mouse glioblastoma and spares circulating antigen reactive CD8+T-cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5265.

Manual analysis of histopathological images is often time-consuming and painstaking, and it is also prone to errors arising from subjective evaluation criteria and human mistakes. To address these issues, we created a fully automated workflow (AW) to enumerate jejunal crypts in a microcolony survival assay to quantify gastrointestinal damage from radiation. After obtaining images of jejunal slices from irradiated mice, the AW performed cropping and normalizing of the individual slice images for resolution and color; using deep learning to detect crypts on each slice; using a tailored algorithm to enumerate the crypts; and tabulating and saving the results. A graphical user interface was developed to allow users to review and correct the automated results. Manual counting of crypts exhibited a mean absolute percent deviation of (34 ± 26)% between individuals vs. the group mean across counters, which was reduced to (11 ± 6)% across the 3 most-experienced counters. AW counts deviated from experts’ mean counts by (10 ± 8)%. With a single button press, the AW processed a sample image dataset from 60 mice in a few hours. The AW thereby allowed rapid, automated evaluation of the microcolony survival assay with accuracy comparable to that of trained experts and without subjective inter-observer variation.

Objective. The main goal of this research is to verify the spatial fidelity of radiacoustic imaging (RAI) as a quantitative dosimetric monitoring tool for FLASH radiotherapy (FLASH-RT) in vivo. FLASH-RT delivers therapeutic radiation at ultra-high instantaneous dose rates (>10(6) Gy s(-1)), offering substantial reductions in normal tissue toxicity while maintaining tumor control. However, clinical translation remains limited by the absence of real-time, in vivo dosimetry systems capable of resolving dose delivery at microsecond timescales. Approach. Here, we present an RAI platform that enables volumetric, single-pulse mapping of radiation dose deposition during FLASH-RT in vivo. The system utilizes a 16 & times; 16 ultrasound transducer matrix array with a model-based reconstruction algorithm to generate quantitative, three-dimensional dose maps with single pulse-level temporal resolution. Main results. In both water phantoms and in vivo murine models, RAI demonstrates high concordance with film dosimetry and TOPAS Monte Carlo simulations (3%/3 mm gamma index pass rates greater than 90% for small fields). Significance. This work establishes RAI as a viable technology for real-time, quantitative electron FLASH dosimetry in vivo for the first time, with the potential to support adaptive delivery, improve treatment safety, and facilitate the clinical translation of FLASH-RT.

PURPOSE:Radiation-induced lymphopenia is a frequent side effect of conventional radiation therapy (CONV RT), due to the high radiosensitivity of circulating lymphocytes. Ultra-high dose rate "FLASH" RT may preferentially spare normal tissue while maintaining tumor control. This study evaluates the impact of single-fraction and multifraction thoracic FLASH RT on lymphocyte preservation, apoptosis, and immunosuppressive signaling in mice. METHODS AND MATERIALS:We compared the immunological impact of thoracic FLASH RT and CONV RT in C57BL/6 mice using single-fraction (17 Gy) and multifraction (2 Gy × 5) regimens using the Mobetron (IntraOp). Longitudinal blood sampling was performed at multiple time points postirradiation through facial vein bleed with flow cytometry analysis for CD4+, CD8+, CD19+, and NK cells to assess lymphocyte counts, apoptotic lymphocytes through Annexin V staining, and immune suppression by examining regulatory T cells and PD-1/PD-L1 expression. Mechanistic studies included immunofluorescence and Western blot analyses of splenic tissues to evaluate Chk1 and STAT3 signaling pathways. RESULTS:In single-fraction RT, FLASH significantly reduced lung and heart fibrosis (P <.0001) at 28 weeks post-RT. The FLASH effect was also seen acutely on circulating immune cells, with significantly reduced lymphocyte apoptosis and accelerated recovery of CD4⁺, CD8⁺, CD3⁺, NK, and B cell populations compared to CONV RT in both single-fraction and multifraction regimens. Conversely, CONV RT induced long-lasting increases in regulatory T cells and sustained PD-1 and PD-L1 expression on T- and B-cells at 2- and 5-months postirradiation in both fractionation regimens. Within the spleen, we also found CONV RT induced sustained activation of the Chk1-STAT3 pathway in CD45+ immune cells, which correlates with increased PD-1/PD-L1 expression. CONCLUSIONS:FLASH RT mitigates radiation-induced lymphopenia, reduces lymphocyte apoptosis, and prevents long-term immunosuppression by reduced activation of the Chk1-STAT3 pathway. These findings suggest FLASH RT may confer immunological advantages over CONV RT to enhance therapeutic efficacy.

PURPOSE:Ultra-high dose rate (>40 Gy/s, FLASH) radiation therapy (RT) provides equivalent tumor control while reducing normal tissue toxicity relative to conventional dose rate radiation (CONV) RT. However, the mechanisms underlying the observed FLASH effect are unknown. We hypothesized that preservation of mitochondrial integrity in nontumorigenic cells by FLASH RT could be a key factor in reducing normal tissue toxicity and improving overall treatment outcomes. METHODS AND MATERIALS:We examined mitochondrial health and function after CONV and FLASH in vitro, ex vivo, and in vivo through assays of metabolic flux, mitochondrial membrane potential, mitochondrial reactive oxygen species (ROS), mitochondrial DNA damage and copy number, mitochondrial morphology, and tumor growth and survival. RESULTS:In in vitro assays, murine pancreatic cancer (PDAC) cells showed similar levels of mitochondrial damage in response to CONV and FLASH, but nontumorigenic pancreatic cells were spared by FLASH. Ex vivo measurements recapitulated the in vitro findings, and in vivo, mice bearing subcutaneous LSL-KRASG12D; Trp53fl/+; Ptf1⍺ Cre (KPC) tumors had comparable tumor growth delay with FLASH and CONV, whereas longer survival after FLASH reflected reduced radiation-induced toxicity rather than greater tumor control. CONCLUSIONS:Collectively, these results suggest that FLASH spares mitochondrial function in nontumorigenic cells, but not in PDAC cells. relative to CONV. The preservation of mitochondrial integrity in nontumorigenic cells may be a key mechanism underlying the reduced normal tissue toxicity observed with FLASH RT.

BACKGROUND:FLASH radiotherapy requires precise control and minimal variation of dose per pulse (DPP). However, clinical linear accelerators and their beam control systems are designed to ensure accuracy of the temporally integrated dose and do not control for transient variations in DPP during radiation delivery. PURPOSE:We introduce a robust external beam control system (EBCS) with radiofrequency optimization and beam monitoring that addresses this need. This system was designed to precisely control the output of FLASH-capable electron linear accelerators within a clinical range of energies (6-20 MeV) and to monitor the output by using a beam current transformer. METHODS:An EBCS, using either an internal transmission ion chamber or a multistage beam current transformer, was implemented to support delivery of conventional DPPs and ultrahigh DPPs (UH-DPPs) on a modified clinical linear accelerator. The EBCS was interfaced with the accelerator's gating system, and beam output and stability were maximized by optimizing the accelerating radiofrequency power efficiency through voltage inputs (VEXT) to the automatic frequency control interface while the beam was held. The EBCS performance was tested by characterizing the beam-off latency; beam output stability within and between pulsed deliveries; sensitivity to deviations from optimization solutions; and beam current transformer linearity from conventional DPPs to UH-DPPs. RESULTS:The measured beam-off latency of the system was 56.7 µs (± 4.9 µs). The radiofrequency optimization was shown to reduce the DPP variability within the first five pulses from 26.7% to less than 0.5% for both conventional DPPs and UH-DPPs. Total output was reduced by up to 20% when VEXT voltage inputs varied from the optimal solution by more than ± 10%. CONCLUSION:We developed an EBCS capable of delivering reproducible doses and implemented it on a modified clinical linear accelerator. Through real time readout of the beam current transformer signal and automatic radiofrequency optimization, the uncertainty in DPP within and between each delivery was reduced to < 0.5%, offering unprecedented precision and accuracy.

Purpose:Osteosarcoma is the most common primary bone malignancy in children and adolescents. Radiotherapy is limited by intrinsic radioresistance and the risk of severe long-term musculoskeletal toxicities. FLASH radiotherapy, delivered at ultra-high dose rates (>40 Gy/s), has demonstrated normal tissue sparing in preclinical models, but its effects on the developing skeleton and marrow remain poorly defined. This study evaluated the chronic normal tissue effects of proton FLASH in juvenile mice, modeling the pediatric context. Methods and Materials:Juvenile C57BL/6 mice (3-4 weeks old) were randomized to receive 11 Gy FLASH (≈200 Gy/s) or conventional proton irradiation (0.2 Gy/s average), or sham treatment to the left hind leg using a synchrotron-based proton beamline. Mice were followed for 10 weeks post-treatment. Bone toxicity was assessed with microCT (bone mineral density, bone volume fractions, trabecular indices) and histology. Bone marrow cellularity was quantified on H&E-stained sections, and muscle fibrosis was assessed using Masson's trichrome. Results:FLASH-treated mice exhibited significant preservation of bone microarchitecture compared with conventional treated mice, with higher bone mineral density and bone volume fractions (p < 0.05). Trabecular numbers were maintained, while structure model index indicates a mechanically favorable trabecular structures in the FLASH group. Bone marrow cellularity was preserved in FLASH mice (5.3% reduction vs. sham) compared with conventional (11.3 % reduction, p < 0.05). Muscle fibrosis was significantly lower in FLASH group (fibrosis positivity 2.6 % vs. 3.0% for FLASH vs. conventional CONV, p < 0.05). No severe immobility or weight loss was observed across groups. Conclusions:Proton FLASH significantly reduces long-term bone, marrow, and muscle toxicities in juvenile mice. These findings provide the first demonstration of musculoskeletal sparing in a synchrotron proton FLASH platform and highlight its translational potential for pediatric osteosarcoma.

Background/Objectives: FLASH radiotherapy (RT) has shown potential to reduce normal tissue toxicity compared with conventional (CONV) RT while maintaining tumor control. FLASH RT is characterized by ultra-high dose rate delivery, commonly using mean dose rates ≥ 40 Gy/s and sub-second delivery times. Most preclinical studies have used single-fraction regimens, leaving the feasibility and normal tissue impact of clinically relevant fractionation largely unexplored. We evaluated electron FLASH RT given in a standard five-fraction regimen to a porcine skin model, simulating adjuvant treatment workflow for high-risk cutaneous melanoma. Method: Three Yorkshire-Landrace swine received paired five-fraction electron irradiations to dorsolateral skin using either FLASH RT (mean dose rates 175-246 Gy/s) or CONV RT (8 Gy/min). Radiation was delivered with a 9-MeV electron beam; field diameters of 4, 7, or 10 cm; and doses of 5 × 6, 5 × 7, or 5 × 8 Gy. Dosimetry was validated with several dosimeters and real-time beam monitoring, confirming dose accuracy within 3%. Skin toxicity was assessed over 22-24 weeks using clinical grading, erythema spectrophotometry, and histopathologic evaluation. Results: FLASH RT was well tolerated at 5 × 6 Gy and 5 × 7 Gy, with no significant differences in peak radiation dermatitis, erythema index, or histologic damage compared with CONV RT. At 5 × 8 Gy, both modalities caused unacceptable toxicity, including moist desquamation and necrosis. No volume-dependent effects were observed. Conclusions: Although a FLASH-specific normal tissue sparing effect was not observed, this study demonstrates the technical feasibility and safety of delivering fractionated electron FLASH RT in a large animal model using a clinically relevant workflow. These findings support further investigation of physical beam parameters and biological modifiers, such as tissue oxygenation, and inform the clinical translation of fractionated FLASH RT for cutaneous malignancies.

Objectives: This project aimed to detail the response of the Standard Imaging Exradin-W2 plastic scintillator detector (PSD) as a function of accumulated dose under ultra-high dose rate (UHDR) electron beams. Approach: This experiment was performed with 9 PSDs and 3 clear optical guide fibers to distinguish between the radiation damage response of the optical guide and the response of the scintillator. The PSDs and the transmitting optical fibers were exposed to a 9 MeV electron beam using a Mobetron electron linear accelerator (IntraOp) at a dose per pulse (DPP) of 3 and 8 Gy, reaching a total cumulative dose of 12 kGy. The PSD's response to both conventional dose rate (CDR) and UHDR irradiation was measured in triplicate prior to any radiation exposure. Conventional and UHDR irradiations were repeated at various increasing doses to assess changes in the sensitivity of the detector. The high dose irradiations were always performed under UHDR. After 2 months with no radiation exposure, the detectors and fibers underwent irradiation regimens identical to the initial ones to quantify their recovery. Main results: The Exradin-W2 PSD blue channel exhibited an average sensitivity loss of (2.0 f 0.2) %/kGy under UHDR and similar loss was found for CDR. The optical fiber showed a mean response decrease of (1.2 f 0.1) %/kGy for UHDR. When irradiating the optical fiber of three W2s, the average sensitivity loss in the blue signal was (6.4 f 0.2) %/kGy for CDR and (6.3 f 0.2) %/kGy for UHDR. Mean response recovery of 10 f 3 % was observed for detectors exposed to conventional beams and (18 f 4) % for UHDR for the blue channel. Overall, the W2 PSD's response (blue and green channels) remained within 3 % of the initial baseline measurement when the cumulative dose was under 2 kGy. Significance: Our results indicate that the W2 PSD exhibited greater sensitivity loss under UHDR than conventional beams found in prior studies. The results suggest that varying DPP does not change the sensitivity loss of the W2. We noted a decrease of the blue channel relative to the green channel in the optical fiber response, which adds to the overall radiation damage to the PSD. Therefore, users should track cumulative dose and recalibrate after each 2 kGy of exposure.

131I (iodide) accumulates in the thyroid and may affect thyroid tissue. Mechanisms behind such effects are not known. The aim was to investigate early changes in protein expression in thyroid and plasma from mice injected with 131I as iodide. Female Balb/c nude mice were i.v. injected with 0 or 490 kBq 131I and killed after 24 h. Thyroid and blood samples were collected from each animal. Protein levels were determined by mass spectrometry. Data are available via ProteomeXchange with identifier PXD062861. Altogether, 17 and 20 proteins showed statistically significant altered levels in thyroid gland and plasma, respectively, after 131I exposure. Most of these proteins had decreased and increased levels in thyroid and plasma, respectively. Few of them were previously proposed radiation responsive proteins. Functional annotation suggests impact on haematopoiesis, reduced oxygen levels, and hypothyroidism. The role of CHIA and PGAM2 in radiation-induced response should be further examined, together with identification and validation of biomarkers of 131I exposure.