The role of medical physics experts in clinical trials: A guideline from the European Federation of Organisations for Medical Physics.

The EFOMP working group on the Role of Medical Physics Experts (MPEs) in Clinical Trials was established in 2010, with experts from across Europe and different areas of medical physics. Their main aims were: (1) To develop a consensus guidance document for the work MPEs do in clinical trials across Europe. (2) Complement the work by American colleagues in AAPM TG 113 and guidance from National Member Organisations. (3) To cover external beam radiotherapy, brachytherapy, nuclear medicine, molecular radiotherapy, and imaging. This document outlines the main output from this working group. Giving guidance to MPEs, and indeed all Medical Physicists (MP) and MP trainees wishing to work in clinical trials. It also gives guidance to the wider multidisciplinary team, advising where MPEs must legally be involved, as well as highlighting areas where MPEs skills and expertise can really add value to clinical trials.

Enhancement of gold-curcumin nanoparticle mediated radiation response for improved therapy in cervical cancer: a computational approach and predictive pathway analysis.

Radiotherapy is prevalently applied for highly effective cancer therapy while the low specificity of radiation is deleterious to the nearby healthy cells. High-Z-based nanomaterials offer excellent radio-enhancement properties while natural products provide radioprotection. Modulation of the radiotherapeutic index via applying nanomaterials is feasible for effective treatment however, the scenario changes when simultaneous protection of non-cancerous cells is required. Here, we report the modulatory radiotherapeutic effect of curcumin conjugated gold nanoparticles in a single nanoformulation to pave the long-awaited hope of a single combination-based, cell-selective radio enhancer, and protectant for cancer radiotherapy. We have validated the effective radiation dose along with the combination of the radio-nano-modulator by a reverse experimentation statistical model. The concept was supported by different sets of experiments, like quantification of ROS generation, cell cycle monitoring, mitochondrial membrane potential measurement, etc. along with gene expression study, and predictive modeling of molecular pathways of the killing mechanism. In conclusion, the nanoconjugate showed a promise to become a candidate for the pH-dependent cell-specific radio-modulator.

Radiation protection of sodium alginate and its regulatory effect on intestinal microflora in mice.

Prolonged or high-dose exposure to ionizing radiation (IR) can cause damage to normal tissues of the body. Therefore, it is imperative to find effective radiation protective agents to mitigate IR-induced damage. This study evaluated the effects of sodium alginate (SA) on the radiation protection and modulatory effects of gut microorganisms using a 60Coγ-induced damage model in mice. Results showed that SA could reduce the damage of hematopoietic system; and alleviate the oxidative damage in irradiated mice by inhibiting the content of malondialdehyde (MDA) and increasing the activities of superoxide dismutase (SOD) and glutathione (GSH) in serum, spleen, jejunum and liver. Moreover, SA treatment ameliorated IR-induced small intestine lesions and alleviated liver injury. This was consistent with decreased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α), and increased levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) after SA treatment. Furthermore, SA treatment reversed IR-induced gut dysbiosis, elevated the Firmicutes/Bacteroidetes ratio, increased the beneficial bacteria and reduced the pathogenic bacteria in the small intestine. In conclusion, the present study demonstrated that SA exerted good radioprotective effect by improving hematopoietic system, alleviating oxidative stress, attenuating liver injury and inflammatory response, and modulating the intestinal microbiota in irradiated mice.

Melatonin as a preventive treatment of tongue mucosa alterations in an animal model of orofacial radiation

Objective: To evaluate the effect of melatonin as a protective treatment for the tongue in irradiated rats. Materials and Methods: Male Sprague Dawley rats were subjected to a single session of 50 Gy radiation and treated with melatonin 30 minutes before and after the radiotherapy session. A clinical evaluation was carried out a week and a half, third- and sixth-week post-treatment; finally, a tongue biopsy was taken for a histopathological study in the third and sixth weeks after radiation. Results: Clinical evaluation shows a clear trend, that preventive administration of melatonin could facilitate the recovery of mucosal tissue after radiation. Additionally, cellular infiltrate was 40% fewer in the melatonin-treated group compared to the control, as well as the number of the congested vessel were fewer. Conclusion: These findings showed for the first time the preventive role of melatonin in the tongue mucosa reducing the changes associated with mucositis, inflammatory infiltrate, and congestive blood vessels.

Does it run in the family? - Improving radiological risk assessment in the coastal environment using taxonomic and phylogenetic perspectives in macroalgae species.

Marine macroalgae are widely used indicator species for monitoring environmental radioactivity. Empirical studies have demonstrated a range in radionuclide transfer coefficients, or concentration ratios (CRs), between taxonomic groups, however the CR values used for dose estimation assume that macroalgae are a homogenous group, represented by a single CR. This study demonstrates the presence of a taxonomic signal in macroalgae CRs for multiple anthropogenic and naturally occurring radionuclides (137Cs, 241Am, 239+240Pu, 210Po) based on a collation of available data. A Residual Maximum Likelihood (REML) mixed model was applied, producing relative estimate CRs specific to each species within the datasets. The collated data was also analysed for a phylogenetic signal, but only a weak signal was found for one radionuclide in one group (239+240Pu in Phaeophyceae). A theoretical case study using the estimated CRs and the ERICA tool was carried out to demonstrate the implications of these findings in a real-world scenario.

The use of Dose Management Systems in Europe: Results of an ESR EuroSafe Imaging Questionnaire.

Dose management systems (DMS) are an essential tool for quality assurance and optimising patient radiation exposure. For radiologists and medical physicists, they are important for managing many radiation protection tasks. In addition, they help fulfil the requirements of Directive 2013/59/EURATOM regarding the electronic transmission of dosimetric data and the detection of unintended patient exposures. The EuroSafe Imaging Clinical Dosimetry and Dose Management Working Group launched a questionnaire on the use of DMS in European member states and analysed the results in terms of modalities, frequency of radiological procedures, involvement of medical physics experts (MPEs), legal requirements, and local issues (support by information technology (IT), modality interfaces, protocol mapping, clinical workflow, and associated costs). CRITICAL RELEVANCE STATEMENT: Despite the great advantages of dose management systems for optimising radiation protection, distribution remains insufficient. This questionnaire shows that reasons include: a lack of DICOM interfaces, insufficient harmonisation of procedure names, lack of medical physicist and IT support, and costs. KEY POINTS: Quantitative radiation dose information is essential for justification and optimisation in medical imaging. Guidelines are required to ensure radiation dose management systems quality and for acceptance testing. Verifying dose data management is crucial before dose management systems clinical implementation. Medical physics experts are professionals who have important responsibilities for the proper management of dose monitoring.

Physiological Roles of Eumelanin- and Melanogenesis-Associated Diseases: A Look at the Potentialities of Engineered and Microbial Eumelanin in Clinical Practice.

This paper aims to highlight the physiological actions exerted by eumelanin present in several organs/tissues of the human body and to rationalise the often conflicting functional roles played by this biopolymer on the basis of its peculiar properties. Besides pigmentary disorders, a growing number of organ injuries and degenerative pathologies are presently ascribed to the modification of physiological eumelanin levels in terms of alterations in its chemical/structural features, and of a partial loss or uneven distribution of the pigment. The present review analyses the more recent research dedicated to the physiological and pathological actions of eumelanin and provides an insight into some melanogenesis-associated diseases of the skin, eye, ear, and brain, including the most significant neurodegenerative disorders. Also described are the potentialities of therapies based on the localised supply of exogeneous EU and the opportunities that EU produced via synthetic biology offers in order to redesign therapeutical and diagnostic applications.

The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector. As such, it might contribute greatly to the safety and wellbeing of individuals exposed to high levels of radiation, whether in planned events (e.g. astronauts) or in unplanned events (e.g. first responders in nuclear accidents).

Monitoring of surgical staff x-ray exposure in the operating room with DosiBadge.

Surgical procedures involving the use of x-rays in the operating room (OR) have increased in recent years, thereby increasing the exposure of OR staff to ionizing radiation. An individual dosimeter makes it possible to record the radiation exposure to which these personnel are exposed, but there is a lack of compliance in the wearing of these dosimeters for several practical reasons. This makes the dose results obtained unreliable. To try to improve the rate of dosimeter wearing in the OR, the Dosibadge project studied the association of the individual dosimeter with the hospital access badge, forming the Dosibadge. Through a study performed at the Tours University Hospital in eight different ORs for two consecutive periods of 3 months. The results show a significant increase in the systematic use of the dosimeter thanks to the Dosibadge, which improves the reliability of the doses obtained on the dosimeters and the monitoring of personnel. The increase is especially marked with clinicians. Following these results and the very positive feedback to this first single-centre study, we are then planning a second multicentre study to validate our proof of concept on different sites, with the three brands of individual dosimeters used in France i.e. dosimeters supplied by Dosilab; Landauer and IRSN.

Melatonin as a radioprotective agent against flattening filter and flattening filter-free beam in radiotherapy-induced lung tissue damage.

BACKGROUND: Radiotherapy is a widely used treatment method in oncology, applied by delivering high-energy particles or waves to the tumor tissue. Although tumor cells are targeted with radiotherapy, it can cause acute or long-term damage to healthy tissues. Therefore, the preservation of healthy tissues has been an important subject of various scientific researches. Melatonin has been shown to have a radioprotective effect on many tissues and organs such as liver, parotid gland, brain, and testicles. This study aimed to evaluate the protective effect of melatonin against the radiation at various doses and rates administered to the lung tissue of healthy mice. METHODS: This study was a randomized case-control study conducted with 80 rats comprising 10 groups with eight animals per group. Of the 10 groups, first is the control group, which is not given any melatonin, and second is the group that does not receive RT, which is given only melatonin, and the other eight groups are RT groups, four with melatonin and four without melatonin. RESULTS: There was no statistical difference in terms of histopathological findings in the lung tissue between the second group, which did not receive radiotherapy and received only melatonin, and the control group. Lung damage due to radiotherapy was statistically significantly higher in the groups that did not receive melatonin compared to the groups that received melatonin. CONCLUSIONS: This study revealed that melatonin has a protective effect against the cytotoxic damage of RT in rats receiving RT.

Bacterial supplementation in mitigation of radiation-induced gastrointestinal damage.

Pelvic irradiation, a crucial treatment for pelvic malignancies, is associated with the risk of gastrointestinal (GI) damage due to the high proliferation rate of epithelial cells. The radiosensitive gastrointestinal tract acts as a dose-limiting organ. High doses of ionizing radiation can cause inflammation and rupture of mucosal barriers and can also lead to intestinal fibrosis. Intestinal damage can cause acute to chronic complications, reducing patients' quality of life. The gut microbiota plays a vital role in maintaining gut health, and any changes in the gut microbial composition can worsen damage, emphasizing the importance of therapies that target and sustain the gut microbiota during radiotherapy. One potential strategy to prevent radiation-induced GI damage is to use bacterial supplements. Research suggests that probiotic supplementation may alleviate radiation-induced gastrointestinal damage, maintaining intestinal morphology and decreasing epithelial injury in cancer patients. The observed protective effects occur through various mechanisms, including antioxidant activities, modulation of the immune response, and preservation of gut barrier function. To optimize probiotic therapies, it is imperative to elucidate these mechanisms. The efficiency of probiotics as radioprotectors is highly dependent on the time and dose of administration, and their interaction with the host immune system is a key facet of their therapeutic potential. This review explores the potential benefits of bacterial supplementation in mitigating radiation-induced GI damage and the underlying mechanism. This highlights the need for further research to establish standardized protocols and refine probiotic supplementation strategies, underscoring the potential for enhancing therapeutic outcomes in patients undergoing pelvic radiotherapy.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury.

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Neuroprotective Action of Selected Natural Drugs Against Neurological Diseases and Mental Disorders: Potential Use Against Radiation Damage.

Exposure to radiation, ionizing and non-ionizing radiation, is a significant concern in modern society. The brain is the organ that is most sensitive to radiation exposure. This review describes how exposure to radiation can affect neurotransmitters in different brain regions, affecting brain function. This review covers neurodegenerative diseases such as Alzheimer's, Parkinson's, and neuroinflammation due to changes in neurons in the central nervous system, and the effects thereon of medicinal plants such as Allium cepa, Allium sativum, Centella asiatica, Coriandrum sativum, and Crocus sativus plants, used for centuries in traditional medicine. These herbal medicines exert free radical scavenging, and antioxidant as well as anti-inflammatory properties which can be beneficial in managing neurological diseases. The present review compiles the neuroprotective effects of selected natural plants against neurological damage, as well as highlights the different mechanisms of action elicited to induce and produce beneficial effects. The current review describes recent studies on the pharmacological effects of neuroprotective herbs on various neurological and mental illnesses, and shows the way further studies can impact this field, including potential effects on radiation-induced damage.

Gut Microbiota-Derived 3-Hydroxybutyrate Blocks GPR43-Mediated IL6 Signaling to Ameliorate Radiation Proctopathy.

Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota-derived 3-hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6-mediated radiation damage. Irradiated cell-fecal microbiota co-culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43-mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut-immune axis in radiation pathophysiology, with potential therapeutic applications.

Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Insights into the radioprotective efficacy of Pterocarpus santalinus L. aqueous extract.

In the present study, we have attempted a comprehensive assessment of the possible radioprotective efficacy of Pterocarpus santalinus aqueous extract (PSAE). All the studied models were gamma-irradiated with prior treatment with PSAE. First, the content of total phenols (4.061 µg/mg gallic acid equivalents), flavonoids (6.616 µg/mg quercetin equivalents), and tannins (0.008 mg/L of PSAE) were determined spectrophotometrically. Second, UHPLC-HRMS analysis was performed to identify the possible radioprotectors. Of those, santalins A & B are known for their usage as natural color in foods and alcoholic beverages identified in PSAE. Treatment was well tolerated with no side effects from PSAE. Later, it was shown that radiation-induced lethality significantly amended in PSAE-treated spleen lymphocytes as evidenced by reduced elevated levels of ROS and lipid peroxidation, restored total thiols and GSH: GSSG, inhibited DNA DSBs and cell death. Furthermore, an immunomodulation study was carried out because radiation exposure induces an inflammatory response. Our study shows that PSAE suppressed concanavalin A-induced T-cell proliferation as evidenced by CFSE dye dilution and CD69 antibody staining methods. Taken together, the current study explored the protective efficacy of PSAE from gamma radiation-inflicted injuries and hence we recommend PSAE as a potent radioprotective formulation.

Ergothioneine-Sodium Hyaluronate Dressing: A Promising Approach for Protecting against Radiation-Induced Skin Injury.

Radiotherapy commonly causes damage to healthy tissues, particularly radiation-induced skin injury (RISI) that affects a significant majority of patients undergoing radiotherapy. Effective treatments for RISI are lacking. This study focuses on the pathogenesis of RISI, which primarily involves oxidative stress. Excessive reactive oxygen species (ROS) generation during radiation induces damage to biological macromolecules, triggering oxidative stress and inflammation. To address this, ergothioneine (EGT), a natural and biocompatibile thiol compound with excellent antioxidant activity, is explored as a potential radiation-protective agent. By utilizing its specific transport and absorption in the skin tissue, as well as its efficient and stable clearance of radiation-induced "ROS storm", EGT is combined with sodium hyaluronate (NaHA) to develop a novel radiation protective dressing suitable for the skin. This EGT-NaHA dressing demonstrates an effective ability to scavenge free radicals and reduce oxidative stress in vitro and in vivo, reducing cellular apoptosis and inflammation. These results demonstrate the protective properties of EGT against RISI, with far-reaching implications for research and development in the field of radioprotection.

A Frog Skin-Derived Peptide Targeting SCD1 Exerts Radioprotective Effects Against Skin Injury by Inhibiting STING-Mediated Inflammation.

The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation-induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation-induced frog skin peptide-2 (RIFSP-2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl-CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP-2 based on streptavidin-biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP-2 following radiation. Moreover, the decreased MUFA limited radiation-induced and STING-mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP-2 and retarded tissue repair process. Altogether, RIFSP-2 restrains radiation-induced activation of SCD1-MUFA-STING axis. Thus, the stress-induced amphibian peptides can be a bountiful source of novel radiation mitigators.

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.

Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements.

PURPOSE: Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups. CONCLUSIONS: Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.