Predictive DNA damage signaling for low­dose ionizing radiation.

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low­dose radiation­sensitive markers. The HuT 78 and IM­9 cell lines were irradiated in a concentration­dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration­dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub­lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub­lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML­277, pifithrin­α, and nutlin­3a were evaluated for their ability to modulate radiation­induced cell death. The use of BML­277 led to a decrease in radiation­induced p­CHK2 and γH2AX levels and mitigated radiation­induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation­sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.

Chromosomal damage, gene expression and alternative transcription in human lymphocytes exposed to mixed ionizing radiation as encountered in space.

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0-2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.

Tardigrades: Trained to be hardy in the face of DNA damage.

Tardigrades withstand ionizing irradiation levels ∼500 times higher than humans can tolerate. Two recent papers shed light on how this might be achieved - via the transcriptional induction of DNA repair genes, the induction of a radioprotective DNA-binding protein, and possibly also the heightened capacity of repair proteins.

RadPhysBio: A Radiobiological Database for the Prediction of Cell Survival upon Exposure to Ionizing Radiation.

Based on the need for radiobiological databases, in this work, we mined experimental ionizing radiation data of human cells treated with X-rays, γ-rays, carbon ions, protons and α-particles, by manually searching the relevant literature in PubMed from 1980 until 2024. In order to calculate normal and tumor cell survival α and ß coefficients of the linear quadratic (LQ) established model, as well as the initial values of the double-strand breaks (DSBs) in DNA, we used WebPlotDigitizer and Python programming language. We also produced complex DNA damage results through the fast Monte Carlo code MCDS in order to complete any missing data. The calculated α/ß values are in good agreement with those valued reported in the literature, where α shows a relatively good association with linear energy transfer (LET), but not ß. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, we developed a biophysical prediction model by using machine learning, which showed a good performance for α, while it underscored LET as the most important feature for its prediction. In this study, we designed and developed the novel radiobiological 'RadPhysBio' database for the prediction of irradiated cell survival (α and ß coefficients of the LQ model). The incorporation of machine learning and repair models increases the applicability of our results and the spectrum of potential users.

Emotional Stress Induces Adaptive Response in Rat Lymphocytes to Subsequent Ionizing Radiation Exposure.

We studied the molecular mechanisms of cross-adaptation to ionizing radiation (1 Gy) of lymphocytes isolated from rats subjected to emotional stress. The effects of chronic (CES; various types of stress exposure) and acute (AES; forced swimming) emotional stress in rats on indicators of oxidative stress, cell death, and levels of NRF2 and NOX4 proteins involved in the development of the adaptive response were analyzed in isolated lymphocytes. It was found that stress induced an adaptive response in rat lymphocytes and triggered processes similar to the adaptive response induced by low doses of ionizing radiation: an increase in the level of oxidized DNA and cell death, as well as an increase in the content of NOX4 and NRF2 proteins. In animals subjected to emotional stress, suppressed DNA oxidation in response to irradiation, reduced levels of protective factor NRF2, as well as lymphocyte death were observed.

Mutagenic Effect during Combined Exposure to Ionizing and Non-Ionizing Electromagnetic Radiation.

Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted.

Host microbiome depletion attenuates biofluid metabolite responses following radiation exposure.

Development of novel biodosimetry assays and medical countermeasures is needed to obtain a level of radiation preparedness in the event of malicious or accidental mass exposures to ionizing radiation (IR). For biodosimetry, metabolic profiling with mass spectrometry (MS) platforms has identified several small molecules in easily accessible biofluids that are promising for dose reconstruction. As our microbiome has profound effects on biofluid metabolite composition, it is of interest how variation in the host microbiome may affect metabolomics based biodosimetry. Here, we 'knocked out' the microbiome of male and female C57BL/6 mice (Abx mice) using antibiotics and then irradiated (0, 3, or 8 Gy) them to determine the role of the host microbiome on biofluid radiation signatures (1 and 3 d urine, 3 d serum). Biofluid metabolite levels were compared to a sham and irradiated group of mice with a normal microbiome (Abx-con mice). To compare post-irradiation effects in urine, we calculated the Spearman's correlation coefficients of metabolite levels with radiation dose. For selected metabolites of interest, we performed more detailed analyses using linear mixed effect models to determine the effects of radiation dose, time, and microbiome depletion. Serum metabolite levels were compared using an ANOVA. Several metabolites were affected after antibiotic administration in the tryptophan and amino acid pathways, sterol hormone, xenobiotic and bile acid pathways (urine) and lipid metabolism (serum), with a post-irradiation attenuative effect observed for Abx mice. In urine, dose×time interactions were supported for a defined radiation metabolite panel (carnitine, hexosamine-valine-isoleucine [Hex-V-I], creatine, citric acid, and Nε,Nε,Nε-trimethyllysine [TML]) and dose for N1-acetylspermidine, which also provided excellent (AUROC ≥ 0.90) to good (AUROC ≥ 0.80) sensitivity and specificity according to the area under the receiver operator characteristic curve (AUROC) analysis. In serum, a panel consisting of carnitine, citric acid, lysophosphatidylcholine (LysoPC) (14:0), LysoPC (20:3), and LysoPC (22:5) also gave excellent to good sensitivity and specificity for identifying post-irradiated individuals at 3 d. Although the microbiome affected the basal levels and/or post-irradiation levels of these metabolites, their utility in dose reconstruction irrespective of microbiome status is encouraging for the use of metabolomics as a novel biodosimetry assay.

Radiation-induced DNA double-strand breaks in cortisol exposed fibroblasts as quantified with the novel foci-integrated damage complexity score (FIDCS).

Without the protective shielding of Earth's atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chronic cortisol exposure during spaceflight raises further concerns, although its specific impact on DNA damage and repair remains unknown. This study explorers the effect of different radiation qualities (photons, protons, carbon, and iron ions) on the DNA damage and repair of cortisol-conditioned primary human dermal fibroblasts. Besides, we introduce a new measure, the Foci-Integrated Damage Complexity Score (FIDCS), to assess DNA damage complexity by analyzing focus area and fluorescent intensity. Our results show that the FIDCS captured the DNA damage induced by different radiation qualities better than counting the number of foci, as traditionally done. Besides, using this measure, we were able to identify differences in DNA damage between cortisol-exposed cells and controls. This suggests that, besides measuring the total number of foci, considering the complexity of the DNA damage by means of the FIDCS can provide additional and, in our case, improved information when comparing different radiation qualities.

[Fatal radiation-induced injury resulting from the deliberate use of ionizing radiation source for illegal purposes]. / Smertel'naya radiatsionnaya travma vsledstvie umyshlennogo primeneniya istochnika ioniziruyushchego izlucheniya v protivopravnykh tselyakh.

A rare clinical observation of death from prolonged uneven external irradiation due to the deliberate use of an ionizing radiation source for illegal purposes has been presented. The main difficulties of postmortem diagnosis of this type of radiation-induced injury, considering the features of histological examinations and special methods of retrospective dosimetric evaluations, have been identified.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

The clinical manifestations and molecular pathogenesis of radiation fibrosis.

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.

IRAK1 deficiency potentiates the efficacy of radiotherapy in repressing cervical cancer development.

IRAK1 has been implicated in promoting development of various types of cancers and mediating radioresistance. However, its role in cervical cancer tumorigenesis and radioresistance, as well as the potential underlying mechanisms, remain poorly defined. In this study, we evaluated IRAK1 expression in radiotherapy-treated cervical cancer tissues and found that IRAK1 expression is negatively associated with the efficacy of radiotherapy. Consistently, ionizing radiation (IR)-treated HeLa and SiHa cervical cancer cells express a lower level of IRAK1 than control cells. Depletion of IRAK1 resulted in reduced activation of the NF-κB pathway, decreased cell viability, downregulated colony formation efficiency, cell cycle arrest, increased apoptosis, and impaired migration and invasion in IR-treated cervical cancer cells. Conversely, overexpressing IRAK1 mitigated the anti-cancer effects of IR in cervical cancer cells. Notably, treatment of IRAK1-overexpressing IR-treated HeLa and SiHa cells with the NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) partially counteracted the effects of excessive IRAK1. Furthermore, our study demonstrated that IRAK1 deficiency enhanced the anti-proliferative role of IR treatment in a xenograft mouse model. These collective observations highlight IRAK1's role in mitigating the anti-cancer effects of radiotherapy, partly through the activation of the NF-κB pathway. SUMMARY: IRAK1 enhances cervical cancer resistance to radiotherapy, with IR treatment reducing IRAK1 expression and increasing cancer cell vulnerability and apoptosis.

Health Effects of Ionizing Radiation on the Human Body.

Radioactivity is a process in which the nuclei of unstable atoms spontaneously decay, producing other nuclei and releasing energy in the form of ionizing radiation in the form of alpha (α) and beta (ß) particles as well as the emission of gamma (γ) electromagnetic waves. People may be exposed to radiation in various forms, as casualties of nuclear accidents, workers in power plants, or while working and using different radiation sources in medicine and health care. Acute radiation syndrome (ARS) occurs in subjects exposed to a very high dose of radiation in a very short period of time. Each form of radiation has a unique pathophysiological effect. Unfortunately, higher organisms-human beings-in the course of evolution have not acquired receptors for the direct "capture" of radiation energy, which is transferred at the level of DNA, cells, tissues, and organs. Radiation in biological systems depends on the amount of absorbed energy and its spatial distribution, particularly depending on the linear energy transfer (LET). Photon radiation with low LET leads to homogeneous energy deposition in the entire tissue volume. On the other hand, radiation with a high LET produces a fast Bragg peak, which generates a low input dose, whereby the penetration depth into the tissue increases with the radiation energy. The consequences are mutations, apoptosis, the development of cancer, and cell death. The most sensitive cells are those that divide intensively-bone marrow cells, digestive tract cells, reproductive cells, and skin cells. The health care system and the public should raise awareness of the consequences of ionizing radiation. Therefore, our aim is to identify the consequences of ARS taking into account radiation damage to the respiratory system, nervous system, hematopoietic system, gastrointestinal tract, and skin.

A novel ionizing radiation-induced small RNA, DrsS, promotes the detoxification of reactive oxygen species in Deinococcus radiodurans.

A plethora of gene regulatory mechanisms with eccentric attributes in Deinoccocus radiodurans confer it to possess a distinctive ability to survive under ionizing radiation. Among the many regulatory processes, small RNA (sRNA)-mediated regulation of gene expression is prevalent in bacteria but barely investigated in D. radiodurans. In the current study, we identified a novel sRNA, DrsS, through RNA-seq analysis in D. radiodurans cells while exposed to ionizing radiation. Initial sequence analysis for promoter identification revealed that drsS is potentially co-transcribed with sodA and dr_1280 from a single operon. Elimination of the drsS allele in D. radiodurans chromosome resulted in an impaired growth phenotype under γ-radiation. DrsS has also been found to be upregulated under oxidative and genotoxic stresses. Deletion of the drsS gene resulted in the depletion of intracellular concentration of both Mn2+ and Fe2+ by ~70% and 40%, respectively, with a concomitant increase in carbonylation of intracellular protein. Complementation of drsS gene in ΔdrsS cells helped revert its intracellular Mn2+ and Fe2+ concentration and alleviated carbonylation of intracellular proteins. Cells with deleted drsS gene exhibited higher sensitivity to oxidative stress than wild-type cells. Extrachromosomally expressed drsS in ΔdrsS cells retrieved its oxidative stress resistance properties by catalase-mediated detoxification of reactive oxygen species (ROS). In vitro binding assays indicated that DsrS directly interacts with the coding region of the katA transcript, thus possibly protecting it from cellular endonucleases in vivo. This study identified a novel small RNA DrsS and investigated its function under oxidative stress in D. radiodurans. IMPORTANCE: Deinococcus radiodurans possesses an idiosyncratic quality to survive under extreme ionizing radiation and, thus, has evolved with diverse mechanisms which promote the mending of intracellular damages caused by ionizing radiation. As sRNAs play a pivotal role in modulating gene expression to adapt to altered conditions and have been delineated to participate in almost all physiological processes, understanding the regulatory mechanism of sRNAs will unearth many pathways that lead to radioresistance in D. radiodurans. In that direction, DrsS has been identified to be a γ-radiation-induced sRNA, which is also induced by oxidative and genotoxic stresses. DrsS appeared to activate catalase under oxidative stress and detoxify intracellular ROS. This sRNA has also been shown to balance intracellular Mn(II) and Fe concentrations protecting intracellular proteins from carbonylation. This novel mechanism of DrsS identified in D. radiodurans adds substantially to our knowledge of how this bacterium exploits sRNA for its survival under stresses.

Bridging clinical radiotherapy and space radiation therapeutics through reactive oxygen species (ROS)-triggered delivery.

This review explores the convergence of clinical radiotherapy and space radiation therapeutics, focusing on ionizing radiation (IR)-generated reactive oxygen species (ROS). IR, with high-energy particles, induces precise cellular damage, particularly in cancer treatments. The paper discusses parallels between clinical and space IR, highlighting unique characteristics of high-charge and energy particles in space and potential health risks for astronauts. Emphasizing the parallel occurrence of ROS generation in both clinical and space contexts, the review identifies ROS as a crucial factor with dual roles in cellular responses and potential disease initiation. The analysis covers ROS generation mechanisms, variations, and similarities in terrestrial and extraterrestrial environments leading to innovative ROS-responsive delivery systems adaptable for both clinical and space applications. The paper concludes by discussing applications of personalized ROS-triggered therapeutic approaches and discussing the challenges and prospects of implementing these strategies in clinical radiotherapy and extraterrestrial missions. Overall, it underscores the potential of ROS-targeted delivery for advancing therapeutic strategies in terrestrial clinical settings and space exploration, contributing to human health improvement on Earth and beyond.

Modulation of epithelial-mesenchymal transition by gemcitabine: Targeting ionizing radiation-induced cellular senescence in lung cancer cell.

Ionizing radiation, a standard therapeutic approach for lung cancer, often leads to cellular senescence and the induction of epithelial-mesenchymal transition (EMT), posing significant challenges in treatment efficacy and cancer progression. Overcoming these obstacles is crucial for enhancing therapeutic outcomes in lung cancer management. This study investigates the effects of ionizing radiation and gemcitabine on lung cancer cells, with a focus on induced senescence, EMT, and apoptosis. Human-derived A549, PC-9, and mouse-derived Lewis lung carcinoma cells exposed to 10 Gy X-ray irradiation exhibited senescence, as indicated by morphological changes, ß-galactosidase staining, and cell cycle arrest through the p53-p21 pathway. Ionizing radiation also promoted EMT via TGFß/SMAD signaling, evidenced by increased TGFß1 levels, altered EMT marker expressions, and enhanced cell migration. Gemcitabine, a first-line lung cancer treatment, was shown to enhance apoptosis in senescent cells caused by radiation. It inhibited cell proliferation, induced mitochondrial damage, and triggered caspase-mediated apoptosis, thus mitigating EMT in vitro. Furthermore, in vivo studies using a lung cancer mouse model revealed that gemcitabine, combined with radiation, significantly reduced tumor volume and weight, extended survival, and suppressed malignancy indices in irradiated tumors. Collectively, these findings demonstrate that gemcitabine enhances the therapeutic efficacy against radiation-resistant lung cancer cells, both by inducing apoptosis in senescent cells and inhibiting EMT, offering potential improvements in lung cancer treatment strategies.

Radiation protection in a cohort of healthcare workers: knowledge, attitude, practices, feelings and IR-exposure in French hospitals.

The number of healthcare workers occupationally exposed to ionizing radiation (IR) is increasing every year. As health effects from exposure to low doses IR have been reported, radiation protection (RP) in the context of occupational activities is a major concern. This study aims to assess the compliance of healthcare workers with RP policies, according to their registered cumulative dose, profession, and perception of radiation self-exposure and associated risk. Every healthcare worker from one of the participating hospitals in France with at least one dosimetric record for each year 2009, 2014, and 2019 in the SISERI registry was included and invited to complete an online questionnaire including information on the worker's occupational exposure, perception of IR-exposure risk and RP general knowledge. Hp(10) doses were provided by the SISERI system. Multivariate logistic regressions were used. Dosimeter wearing and RP practices compliance were strongly associated with 'feeling of being IR-exposed' (OR = 3.69, CI95% 2.04-6.66; OR = 4.60, CI95% 2.28-9.30, respectively). However, none of these factors was associated with RP training courses attendance. The main reason given for non-compliance is unsuitability or insufficient numbers of RP devices. This study provided useful information for RP policies. Making exposed workers aware of their own IR-exposure seems to be a key element to address in RP training courses. This type of questionnaire should be introduced into larger epidemiological studies. Dosimeter wearing and RP practices compliance are associated to feeling being IR-exposed. RP training courses should reinforce workers' awareness of their exposure to IR.

Dynamic role of CUL4B in radiation-induced intestinal injury-regeneration.

CUL4B, a crucial scaffolding protein in the largest E3 ubiquitin ligase complex CRL4B, is involved in a broad range of physiological and pathological processes. While previous research has shown that CUL4B participates in maintaining intestinal homeostasis and function, its involvement in facilitating intestinal recovery following ionizing radiation (IR) damage has not been fully elucidated. Here, we utilized in vivo and in vitro models to decipher the role of CUL4B in intestinal repair after IR-injury. Our findings demonstrated that prior to radiation exposure, CUL4B inhibited the ubiquitination modification of PSME3, which led to the accumulation of PSME3 and subsequent negative regulation of p53-mediated apoptosis. In contrast, after radiation, CUL4B dissociated from PSME3 and translocated into the nucleus at phosphorylated histones H2A (γH2AX) foci, thereby impeding DNA damage repair and augmenting p53-mediated apoptosis through inhibition of BRCA1 phosphorylation and RAD51. Our study elucidated the dynamic role of CUL4B in the repair of radiation-induced intestinal damage and uncovered novel molecular mechanisms underlying the repair process, suggesting a potential therapeutic strategy of intestinal damage after radiation therapy for cancers.

Patient perspectives on ionising radiation exposure from computed tomography in Saudi Arabia: a knowledge and perception study.

The objective of this study was to evaluate patient knowledge and understanding of ionising radiation and dosage, as well as the accompanying risks related to computed tomography scans. A total of 412 outpatients who underwent computed tomography (CT) scans were surveyed to assess their understanding of radiation dose and exposure risks. CT was correctly classified as an ionising radiation by 56.8% of the respondents. More than half of the patients reported that a CT scan increases the probability of inducing cancer. Awareness of varying radiation doses in different CT exams was noted in 75.2% of patients, but only 21.4% reported having discussions with their physician about radiation dose. Gender, age and employment were significantly correlated with knowledge levels. The survey findings indicate a limited understanding of the hazards associated with ionising radiation used in CT scans, highlighting a need for increased awareness and education on radiation protection to ensure informed consent.

Use of a dosimetry-based RAI protocol for treatment of benign hyperthyroidism optimises response while minimising exposure to ionising radiation.

BACKGROUND: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. METHODS: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non-hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. RESULTS: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry-based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p = .64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. CONCLUSION: This retrospective clinical study demonstrated that treatment with a dosimetry-based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI.