Radiobiological Effects Research Articles

Iodinated Copper–Cysteamine Nanoparticles as Radiosensitizers for Tumor Radiotherapy

Background/Objectives: Radiotherapy is a widely applied first-line clinical treatment modality of cancer. Copper–cysteamine (Cu-Cy) nanoparticles represent a new type of photosensitizer that demonstrates significant anti-tumor potential by X-ray-induced photodynamic therapy. Iodide is a high-Z element with superior X-ray absorption ability and has the β-decay radiotherapeutic nuclide, 131I, which emits Cherenkov light. In this study we aimed to investigate the X-ray-induced photodynamic therapy potential of iodinated Cu-Cy (Cu-Cy-I) nanoparticles and also explore the local treatment efficacy of 131I-labeled Cu-Cy-I ([131I]Cu-Cy-I) nanoparticles. Methods: The synthesis of [131I]Cu-Cy-I nanoparticles was performed with [131I]I− anions. The in vitro radiobiological effects on tumor cells incubated with Cu-Cy-I nanoparticles by X-ray irradiation were investigated. The in vivo tumor growth-inhibitory effects of the combination of Cu-Cy-I nanoparticles with X-ray radiotherapy and [131I]Cu-Cy-I nanoparticles were evaluated with 4T1 tumor-xenografted mice. Results: The in vitro experiment results indicated that the X-ray irradiation with the presence of Cu-Cy-I nanoparticles produced a higher intracellular reactive oxygen species (ROS) level and more DNA damage of 4T1 cells and showed a stronger tumor cell killing ability compared to X-ray irradiation alone. The in vivo experimental results with 4T1 breast carcinoma-bearing mice showed that the combination of an intratumoral injection of Cu-Cy-I nanoparticles and X-ray radiotherapy enhanced the tumor growth-inhibitory effect and prolonged the mice’s lives. Conclusions: Cu-Cy-I nanoparticles have good potential as new radiosensitizers to enhance the efficacy of external X-ray radiotherapy. However, the efficacy of local treatment with [131I]Cu-Cy-I nanoparticles at a low 131I dose was not verified. The effective synthesis of smaller sizes of nanoparticles is necessary for further investigation of the radiotherapy potential of [131I]Cu-Cy-I nanoparticles.

Very High-Energy Electron Therapy Toward Clinical Implementation.

The use of very high energy electron (VHEE) beams, with energies between 50 and 400 MeV, has drawn considerable interest in radiotherapy due to their deep tissue penetration, sharp beam edges, and low sensitivity to tissue density. VHEE beams can be precisely steered with magnetic components, positioning VHEE therapy as a cost-effective option between photon and proton therapies. However, the clinical implementation of VHEE therapy (VHEET) requires advances in several areas: developing compact, stable, and efficient accelerators; creating sophisticated treatment planning software; and establishing clinically validated protocols. In addition, the perspective of VHEE to access ultra-high dose-rate regime presents a promising avenue for the practical integration of FLASH radiotherapy of deep tumors and metastases with VHEET (FLASH-VHEET), enhancing normal tissue sparing while maintaining the inherent dosimetric advantages of VHEET. However, FLASH-VHEET systems require validation of time-dependent dose parameters, thus introducing additional technological challenges. Here, we discuss recent progress in VHEET research, focusing on both conventional and FLASH modalities, and covering key aspects including dosimetric properties, radioprotection, accelerator technology, beam focusing, radiobiological effects, and clinical outcomes. Furthermore, we comprehensively analyze initial VHEET in silico studies on coverage across various tumor sites.

Individualized evaluation of the total dose received by radiotherapy patients: Integrating in-field, out-of-field, and imaging doses.

To propose a methodology for integrating the out-of-field and imaging doses to the in-field dose received by radiotherapy (RT) patients. In addition, the impact of considering the total dose in planning and radiation-induced second malignancies (RISM) risk assessment will be evaluated in several scenarios comprising photon and proton treatments. The total dose is the voxel-wise sum of the doses from the different radiation sources (accounting for the radiobiological effectiveness) produced during the whole RT chain. The dose from the plan and imaging procedures were obtained by measurements for a photon prostate treatment and by calculation (combining treatment planning system, analytical models, and Monte Carlo simulations) for two lymphoma treatments, one using photons and the other, protons. Dose distributions, dose volume histograms (DVHs) metrics, mean organ doses, and RISM risks were evaluated for each radiation exposure in each treatment. In general, the contribution of the imaging doses is low compared to the dose administered during RT treatment, being higher in proton therapy. However, for some organs, for instance testes in the prostate case, the imaging dose becomes higher than the scattered dose from the treatment fields. Plan evaluations revealed shifts in cumulative DVHs with the inclusion of out-of-field and imaging doses, though minimal clinical impact is expected. Risk assessment showed increased estimates with total dose. The methodology enables accounting for the total dose for optimization of plans and imaging protocols, prospective risk predictions and retrospective epidemiological analyses.

NGS Detects Extensive Genomic Alterations in Survivors of Irradiated Normal Human Fibroblast Cells.

It is thought that cells surviving ionizing radiation exposure repair DNA double-strand breaks (DSBs) and restore their genomes. However, the recent biochemical and genetic characterization of DSB repair pathways reveals that only homologous recombination (HR) can function in an error-free manner and that the non-homologous end joining (NHEJ) pathways canonical NHEJ (c-NHEJ), alternative end joining (alt-EJ), and single-strand annealing (SSA) are error-prone, and potentially leave behind genomic scars and altered genomes. The strong cell cycle restriction of HR to S/G2 phases and the unparalleled efficiency of c-NHEJ throughout the cell cycle, raise the intriguing question as to how far a surviving cell "reaches" after repairing the genome back to its pre-irradiation state. Indeed, there is evidence that the genomes of cells surviving radiation treatment harbor extensive genomic alterations. To directly investigate this possibility, we adopted next-generation sequencing (NGS) technologies and tested a normal human fibroblast cell line, 82-6 hTert, after exposure up to 6 Gy. Cells were irradiated and surviving colonies expanded and the cells froze. Sequencing analysis using the Illumina sequencing platform and comparison with the unirradiated genome detected frequent genomic alterations in the six investigated radiation survivor clones, including translocations and large deletions. Translocations detected by this analysis and predicted to generate visible cytogenetic alterations were frequently (three out of five) confirmed using mFISH cytogenetic analysis. PCR analysis of selected deletions also confirmed seven of the ten examined. We conclude that cells surviving radiation exposure tolerate and pass to their progeny a wide spectrum of genomic alterations. This recognition needs to be integrated into the interpretation of biological results at all endpoints, as well as in the formulation of mathematical models of radiation action. NGS analysis of irradiated genomes promises to enhance molecular cytogenetics by increasing the spectrum of detectable genomic alterations and advance our understanding of key molecular radiobiological effects and the logic underpinning DSB repair. However, further developments in the technology will be required to harness its full potential.

Evaluation of Threshold Levels for Effects of Chronic Exposure of Mammals with Different Life Expectancies

The lower threshold values of the chronic exposure rate, above which negative radiobiological effects appear, are assessed and compared for mammals with low and high natural life expectancy. Dataset has been prepared, containing information on the observed radiobiological effects of chronic irradiation in mammals, depending on the dose rate. The dataset includes 118 records for mammals with high life expectancy and 92 records for mammals with low life expectancy. Data were analyzed with the nonparametric statistics. The lower threshold for deterministic radiation effects of chronic exposure for long-lived mammals is 0,1 mGy/day, with a 95% confidence interval 0.04 – 0.3 mGy/day. For mammals with a short natural life cycle, this threshold value is one order of magnitude higher – 1 mGy/day, with a 95% confidence interval of 0.5–1.1 mGy/day. It is concluded that the quantitative radiation safety criteria for long-lived and short-lived mammal species differ, which should be taken into account when assessing the ecological risk of radioactive contamination of the environment.

Features of internal absorbed dose microdistribution in biological tissue irradiated by 31SiO2 microparticles compared with dose microdistribution from exposure to 56MnO2 particles.

Radiobiological studies are ongoing to understand the consequences of internal exposure to neutron-activated radioactive microparticles, which were sprayed over experimental rats and mice. Special attention in these experiments is given to internal irradiation with radioactive microparticles with short-lived neutron-activated radionuclides 31Si (T1/2 = 2.62h) and 56Mn (T1/2 = 2.58h), which are among the main dose-forming factors from residual radioactivity activated in soils by neutrons in the first hours after atmospheric nuclear explosions. The presented work is devoted to microdosimetry peculiarities of 31SiO2 and 56MnO2 microparticles. The radiation from 31Si consists of intensive short-range beta particles and gamma rays with very low intensity. It differs from the radiation of 56Mn, which includes intensive beta particles, low energy Auger electrons and very intensive gamma rays. Differences in the energies and intensities of short-range beta particles and penetrating gamma rays emitted by 31SiO2 and 56MnO2 microparticles can lead to differences in the spatial microdistribution of absorbed dose around the corresponding radioactive microparticles embedded in biological tissue. It was found in the presented work that the absorbed doses of beta radiation emitted by 56MnO2 and 31SiO2 microparticles has significant but different spatial gradients with distances in biological tissue that correspond to the typical thickness of epithelial cells of lungs' alveoli and bronchioles. The results obtained are necessary for a better understanding of radiobiological effects of internal exposure by radioactive microparticles with 56Mn and 31Si observed in framework of performed and ongoing radiobiological studies with experimental animals-rats and mice.

Mathematical analysis of FLASH effect models based on theoretical hypotheses

Objective.Clinical applications of FLASH radiotherapy require formulas to describe how the FLASH radiation features and other related factors determine the FLASH effect. Mathematical analysis of the models can connect the theoretical hypotheses with the radiobiological effect, which provides the foundation for establishing clinical application models. Moreover, experimental and clinical data can be used to explore the key factors through mathematical analysis.Approach.We abstract the complex models of the oxygen depletion hypothesis and radical recombination-antioxidants hypothesis into concise mathematical equations. The equations are solved to analyze how the radiation features and other factors influence the FLASH effect. Then we propose methodologies for determining the parameters in the models and utilizing the models to predict the FLASH effect.Main results.The formulas linking the physical, chemical and biological factors to the FLASH effect are obtained through mathematical derivation of the equation. The analysis indicates that the initial oxygen concentration, radiolytic oxygen consumption and oxygen recovery are key factors for the oxygen depletion hypothesis and that the level of antioxidants is the key factor for the radical recombination-antioxidants hypothesis. According to the model derivations and analysis, the methodologies for determining parameters and predicting the FLASH effect are proposed: (1) the criteria for data filtration, (2) the strategy of hybrid FLASH and conventional dose rate (CONV) irradiation to ensure the acquisition of effective experimental data across a wide dose range, (3) the pipelines of fitting parameters and predicting the FLASH effect.Significance.This study establishes the quantitative relationship between the FLASH effect and key factors. The derived formulas can be used to calculate the FLASH effect in future clinical FLASH radiotherapy. The proposed methodologies guide to obtain sufficient high-quality datasets and utilize them to predict the FLASH effect. Furthermore, this study indicates the key factors of the FLASH effect and offers clues to further explore the FLASH mechanism.

Understanding Permeability Changes in Vestibular Schwannomas as Part of the Dynamic Response to Radiosurgery Using Golden-Angle Radial Sparse Parallel Imaging: A Retrospective Study

BACKGROUND AND OBJECTIVES: Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on postcontrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. METHODS: Consecutive patients with vestibular schwannoma who underwent SRS between 2017 and 2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 18, and 30 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS (https://gravis-imaging.org/gravis/), an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. RESULTS: The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 18, and 30 months after SRS (corrected P < .05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak (P = .013) and AUC (P = .029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at a median of 62 months. These patients showed a strong correlation between peak, AUC, and wash-in phase slope changes at 6 months and tumor volume at the last follow-up. CONCLUSION: After SRS and loss of internal contrast uptake within vestibular schwannomas, a slow vascular permeability dynamic persisted, suggesting the presence of postradiation processes such as fibrosis. We show for the first time, using GRASP, a quantitative assessment of the vascular radiobiological effect.

Assessing the biological effects of boron neutron capture therapy through cellular DNA damage repair model.

Boron neutron capture therapy (BNCT) is a targeted radiotherapy that relies on the 10B (n, α) 7Li reaction, which produces secondary particles with high linear energy transfer (LET), leading to a high relative biological effectiveness (RBE) in tumors. The biological effectiveness of BNCT is influenced by factors such as boron distribution and concentration, necessitating improved methods for assessing its radiobiological effects and clarifying the sensitivity of the differences in different factors to the biological effects. This paper introduces a method to evaluate the biological effects of BNCT using the cellular repair model. This method aims to overcome some of the limitations of current evaluation approaches. The primary goal is to provide guidance for clinical treatments and the development of boron drugs, as well as to investigate the impact of the synergistic effects of mixed radiation fields in BNCT on treatment outcomes. The approach involves three key steps: first, extending the radial energy deposition distribution of BNCT secondary particles using Geant4-DNA. This allows for the calculation of initial DNA double-strand breaks (DSBs) distributions for a given absorbed dose. Next, the obtained initial DSB distributions are used for DNA damage repair simulations to generate cell survival curves, then thereby quantifying RBE and compound biological effectiveness (CBE). The study also explores the synergistic effects of the mixed radiation fields in BNCT on assessing biological effects were also explored in depth. The results showed that the RBE of boronophenylalanine (BPA) and sodium borocaptate (BSH) drugs at cell survival fraction 0.01 was 2.50 and 2.15, respectively. The CBE of the boron dose component was 3.60 and 0.73, respectively, and the RBE of the proton component was 3.21, demonstrating that BPA has a significantly higher biological impact than BSH due to superior cellular permeability. The proton dose significance in BNCT treatment is also underscored, necessitating consideration in both experimental and clinical contexts. The study demonstrates that synergistic effects between disparate radiation fields lead to increased misrepairs and enhanced biological impact. Additionally, the biological effect diminishes with rising boron concentration, emphasizing the need to account for intercellular DNA damage heterogeneity. This methodology offers valuable insights for the development of new boron compounds and precise assessment of bio-weighted doses in clinical settings and can be adapted to other therapeutic modalities.

Gold Nanoparticles Cause Radiosensitization in 4T1 Cells by Inhibiting DNA Double Strand Break Repair: Single Cell Comparisons of DSB Formation and γH2AX Expression.

Metal nanoparticles sensitize cancers to radiotherapy however their mechanisms of action are complex. The conceptual inspiration arose from theories of physical dose deposition however various chemical and biological factors have also been identified. Interpretation of data has been limited by challenges in measuring true DNA damage compared to DNA damage repair factors. Here, we applied a new assay, STRIDE, for the first time to measure DNA double strand breaks (DSBs) in 4T1 cells as a model of triple negative breast cancer exposed to gold nanoparticles and radiation, and compared this to the common γH2AX assay for DSB repair. The STRIDE assay showed no increase in DSB detection 15 mins after irradiation for cells containing nanoparticles compared to cells without. Gold nanoparticles led to prolonged detection of DSBs after irradiation and delayed the DSB repair. The data show no evidence of increased radiation dose deposition with nanoparticles, but rather enhanced radiobiological effects resulting from nanoparticles which includes disruption of the recruitment of essential DDR machinery, thereby impairing DNA repair processes.

RADT-48. ANALYSIS OF PROTON RADIATION THERAPY INDUCED CONTRAST ENHANCEMENT: A SINGLE INSTITUTION, RETROSPECTIVE STUDY

Abstract Proton radiotherapy (PRT) has superior physical dose distribution with a lesser integral off target radiation dose exposure compared with standard photon radiotherapy resulting in reduced toxicity of uninvolved normal tissues. However, there may be toxicity in areas targeted for high dose treatment as a result of uncertainty about the relative radiobiologic effect (RBE) of proton radiotherapy compared with photon radiotherapy and the potential for localized high doses at the end of the proton beam range (Bragg peak). This may result in radiation-induced contrast enhancement (RICE) reflecting transient toxicity or permanent injury, particularly when associated with concurrent chemotherapy. We analyzed 150 consecutive adult patients, with a histopathologic diagnosis of CNS malignancy, who underwent only PRT at Johns Hopkins Hospital between 2019 – 2023 with least 1 year of follow-up imaging. RICE was defined as a new post-treatment contrast enhancement on MRI within the radiation field. The determination of disease progression or RICE was confirmed with additional follow-up MRI or pathology. RICE was identified in 14 cases (9.3%). The median age was 48 y (range 19 – 72 years), sex 50% female. Diagnosis was 5 astrocytoma, 3 meningioma, 2 glioblastoma, 1 medulloblastoma, 2 oligodendroglioma, 1 tectal glioma. 4/5 astrocytoma patients were grade 2, 2/3 meningioma was grade 1, 1/3 was grade 2, 2/2 oligodendroglioma was grade 2. The median time since completing PRT to development of RICE was 3.5 months. The median radiation dose was 52.20 Gye (range 23.40 - 60.06). Dexamethasone was used in 11 patients (78 %) and in bevacizumab was used 2. Chemotherapy with temozolomide 7 (50%), PCV 1, and none in 5. 12 (85%) patients were still alive. PRT can also be associated with radiation injury in the target, and more information is needed about the incidence, natural history, and associations with localized dosimetry.

AMBER: A Modular Model for Tumor Growth, Vasculature and Radiation Response.

Computational models of tumor growth are valuable for simulating the dynamics of cancer progression and treatment responses. In particular, agent-based models (ABMs) tracking individual agents and their interactions are useful for their flexibility and ability to model complex behaviors. However, ABMs have often been confined to small domains or, when scaled up, have neglected crucial aspects like vasculature. Additionally, the integration into tumor ABMs of precise radiation dose calculations using gold-standard Monte Carlo (MC) methods, crucial in contemporary radiotherapy, has been lacking. Here, we introduce AMBER, an Agent-based fraMework for radioBiological Effects in Radiotherapy that computationally models tumor growth and radiation responses. AMBER is based on a voxelized geometry, enabling realistic simulations at relevant pre-clinical scales by tracking temporally discrete states stepwise. Its hybrid approach, combining traditional ABM techniques with continuous spatiotemporal fields of key microenvironmental factors such as oxygen and vascular endothelial growth factor, facilitates the generation of realistic tortuous vascular trees. Moreover, AMBER is integrated with TOPAS, an MC-based particle transport algorithm that simulates heterogeneous radiation doses. The impact of radiation on tumor dynamics considers the microenvironmental factors that alter radiosensitivity, such as oxygen availability, providing a full coupling between the biological and physical aspects. Our results show that simulations with AMBER yield accurate tumor evolution and radiation treatment outcomes, consistent with established volumetric growth laws and radiobiological understanding. Thus, AMBER emerges as a promising tool for replicating essential features of tumor growth and radiation response, offering a modular design for future expansions to incorporate specific biological traits.

Enhancing Radiation-induced Reactive Oxygen Species Generation Through Mitochondrial Transplantation in Human Glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3020 and U3035. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo .

In silico estimation of polyethylene glycol coating effect on metallic NPs radio-sensitization in kilovoltage energy beams

PurposeNanoparticles (NPs) as radiosensitizers present a promising strategy for enhancing radiotherapy effectiveness, but their potential is significantly influenced by the properties of their surface coating, which can impact treatment outcomes. Most Monte Carlo studies have focused on metallic NPs without considering the impact of coating layers on radiosensitization. In this study, we aim to assess both the physical and radiobiological effects of nanoparticle coatings in nanoparticle-based radiation therapy.Materials and methodsIn this simulation study, we used Geant4 Monte Carlo (MC) toolkit (v10.07.p02) and simulated the bismuth, gold, iridium and gadolinium NPs coated with polyethylene glycol (PEG-400: Density: 1.13 g/cm³, Molar mass: 380–420 g/mol) as radiosensitizer for photon beams of 30, 60 and 100 keV. Secondary electron number and reactive oxygen species enhancement factor were estimated. Also, dose enhancement factor (DEF) was determined in spherical shells with logarithmic scale thickness from the nanoparticle surface to 4 mm.ResultsSecondary electron emission was highest at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs peaked at 60 keV. Coating reduced electron emissions across all energies, with thicker coatings leading to a more significant decrease. DEF values declined with increasing radial distance from the NP surface and were lower with thicker coatings. For gadolinium NPs, DEF behavior differed due to K-edge energy effects. Reactive species generation varied, showing maximum production at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs showed peak activity at 60 keV. PEG coatings enhanced reactive species formation at 100 keV.ConclusionThe findings indicate that the coating layer thickness and material not only influence the emission of secondary particles and DEF but also affect the generation of reactive species from water radiolysis. Specifically, thicker coatings reduce secondary particle emission and DEF, while PEG coatings demonstrate a dual behavior, offering both protective and enhancing effects depending on photon energy. These insights underscore the importance of optimizing NP design and coating in future studies to maximize therapeutic efficacy in nanoparticle-based radiation therapy.

Radiobiological evaluation of the impact of the treatment with the gamma knife radiosurgery technique on the body parts of patients with different brain lesions: Does the radiation exposure affect also the Patient's blood components?

The research aimed to study the safety of the dose-staged Gamma Knife radiosurgery (GKRS) on the patients' organs, by evaluating the equivalent and effective doses delivered to various body parts and examining the impacts on the blood parameters. The case study consisted of 30 patients with different brain lesions undergone to GKRS. To assess the radiation exposure on the different body parts, gamma dose rates were measured using a survey radiation dosimeter. The results demonstrated that the GKRS beam effectively backscatters on the patient's body, considering the irradiation doses and the exposure time. Body parts in closer proximity to the target (radiation beam) received higher gamma doses compared to other areas. High and low values of gamma dose rate were measured in the two configurations: high irradiation dose (80 Gy for 46.47 min) and low irradiation dose (10 Gy per 15.7 min) for the brain lesions of Trigeminal Neuralgia and Meningioma, respectively. Radiobiological effects were estimated following the international guidelines revealing significant radiation impacts on some organs. Hematological effects were also evaluated with variations depending on the radiation exposure dose and the exposure time. Some blood cells showed radiation-related impacts. Notably, the high dose of 80 Gy administered over 46.47 min of exposure for trigeminal brain lesions had a greater influence on the blood parameters compared to the low dose of 10 Gy over 15.7 min of exposure for acoustic neuroma brain lesions. Consequently, it turned out that increases in gamma-ray doses resulted in significant impacts on specific blood parameters.

A comparative study of sensitizers and liposome composition in radiation-induced controlled drug release for cancer therapy

This study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. In vitro analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential.

3187: The applied radiobiological effectiveness model influences tumor control when treating with ions

3187: The applied radiobiological effectiveness model influences tumor control when treating with ions

Assessment of the skin contamination dose coefficients for 252Cf radionuclide: Monte Carlo approach

Handling the 252Cf radionuclide source poses a potential hazard of skin surface contamination in case of an unexpected occurrence. Consequently, there is a growing need to establish precise dose conversion coefficients tailored to each type of emitted primary particle and various radionuclides. Nevertheless, the current body of literature does not provide specific data or methodologies for evaluating skin contamination dose and its associated coefficients, particularly with regard to the 252Cf source. Thus, this study aims to quantify the dose rate received by the skin and its associated coefficients after contamination scenario. Utilizing the established MCNPX environment, the Equivalent dose rate and Absorbed dose, along with Skin contamination dose coefficient (SCDC), have been calculated within the skin tissue. Two methodologies, specifically Watt Fission distribution and the Doppler Effect, are proposed to analyze particle spectra within skin phantom, enabling the calculation of Equivalent dose rate. In accordance with ICRP recommendations regarding the optimal depth for assessing skin doses, the designated scoring volume within the skin is located between depths of 50–100 μm. This volume is tasked with evaluating the dose. The SCDC results were entirely consistent with previously published data from MCNPX, with statistical uncertainties of less than 15%, demonstrating the efficacy of the methodologies employed in this study. This research presents an innovative method for generating data related to skin contamination doses. The novel outcomes in the current research facilitate the assessment of skin dose contamination for the targeted radionuclides and radiotherapy purposes due to staff oversight and radiobiological effects.

Radiation Chemistry and Radiation Research: A History from the Beginning to the Platinum Edition.

At the dawn of the 20th Century, the underlying chemistry that produced the observed effects of ionizing radiation, e.g., X rays and Radium salts, on aqueous solutions was either unknown or restricted to products found postirradiation. For example, the Curies noted that sealed aqueous solutions of Radium inexplicably decomposed over time, even when kept in the dark. By 1928 there were numerous papers describing the phenomenological effects of ionizing radiation on a wide variety of materials, including the irradiated hands of early radiologists. One scientist who became intensely interested in these radiation effects was Hugo Fricke (Fricke Dosimetry) who established a laboratory in 1928 dedicated to studies on chemical effects of radiation, the results of which he believed were necessary to understand observed radiobiological effects. In this Platinum Issue of Radiation Research (70 years of continuous publication), we present the early history of the development of radiation chemistry and its contributions to all levels of mechanistic radiobiology. We summarize its development as one of the four disciplinary pillars of the Radiation Research Society and its Journal, Radiation Research, founded during the period 1952-1954. In addition, the work of scientists who contributed substantially to the discipline of Radiation Chemistry and to the birth, life and culture of the Society and its journal is presented. In the years following 1954, the increasing knowledge about the underlying temporal and spatial properties of the species produced by various types of radiation is summarized and related to its radiobiology and to modern technologies (e.g., pulsed radiolysis, electron paramagnetic resonance) which became available as the discipline of radiation chemistry developed. A summary of important results from these studies on Radiation Chemistry/Biochemistry in the 20th and 21st Century up to the present time is presented. Finally, we look into the future to see what possible directions radiation chemistry studies might take, based upon promising current research. We find at least two possible directions that will need radiation chemistry expertise to ensure proper experimental design and interpretation of data. These are FLASH radiotherapy, and mechanisms underlying the effects of low doses of radiation delivered at low dose rates. Examples of how radiation chemists could provide beneficial input to these studies are provided.

Monte Carlo simulations of microdosimetry and radiolytic species production at long time post proton irradiation using GATE and Geant4-DNA.

Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments. Therefore, in this study, we propose to validate a new Geant4-DNA chemistry module through the simulation of water radiolysis and Fricke dosimetry experiments on a proton preclinical beam line. In this study, we used the GATE Monte Carlo simulation platform (version 9.3) to simulate a 67.5 MeV proton beam produced with the ARRONAX isochronous cyclotron (IBA Cyclone 70XP) at conventional dose rate (0.2Gy/s) to simulate the irradiation of ultra-pure liquid water samples and Fricke dosimeter. We compared the depth dose profile with measurements performed with a plane parallel Advanced PTW 34045 Markus ionization chamber. Then, a new Geant4-DNA chemistry application proposed from Geant4 version 11.2 has been used to assess the evolution of , , , , , , and reactive species along time until 1-h post-irradiation. In particular, the effect of oxygen and pH has been investigated through comparisons with experimental measurements of radiolytic yields for and Fe3+. GATE simulations reproduced, within 4%, the depth dose profile in liquid water. With Geant4-DNA, we were able to reproduce experimental radiolytic yields 1-h post-irradiation in aerated and deaerated conditions, showing the impact of small changes in oxygen concentrations on species evolution along time. For the Fricke dosimeter, simulated G(Fe3+) is 15.97±0.2 molecules/100eV which is 11% higher than the measured value (14.4±04 molecules/100 eV). These results aim to be consolidated by new comparisons involving other radiolytic species, such as or to further study the mechanisms underlying the FLASH effect observed at ultra-high dose rates (UHDR).