Radiobiological Research Articles

Sharing of data archive of radiation exposure animal experiments in QST/NIRS and IES.

Institute for Radiological Science (NIRS), National Institutes for Quantum Science and Technology (QST), and Institute for Environmental Sciences (IES) have conducted large-scale animal experiments for radiation risk analyses in terms of life shortening and cancer prevalence. It is important to store data and biological samples from these large-scale experiments for sharing and future use since the economic and practical limitations, as well as the ethical considerations, make it difficult. QST/NIRS established an archive called the Japan Storehouse of Animal Radiobiology Experiments (J-SHARE) for the purpose of storing and sharing these historic collections. We plan to integrate the data and tissue specimen images obtained at the IES into J-SHARE by standardizing the archive format, with the aim of maximizing the results of radiation biology research. This integration is expected to contribute to the generation of new knowledge for radiation risk assessment and the provision of scientifically based information on radiation protection.

Development of a novel computational technique to create DNA and cell geometrical models for Geant4-DNA

BackgroundThis study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve. MethodsA Python-based tool named “complexDNA” was developed to facilitate the design of both simple and complex DNA geometries. This tool was employed to construct a human cell geometry with individual pairs of chromosomes. Subsequently, the performance of this chromosomal model was compared to the standard human cell model provided in the “molecularDNA” Geant4-DNA example. ResultsSimulations using the new chromosomal model revealed minimal discrepancies in DNA damage yield and fragment size distribution compared to the default human cell model. Notably, the chromosomal model demonstrated significant computational efficiency, requiring approximately three times less simulation time to achieve equivalent results. ConclusionsThis work highlights the importance of incorporating chromosomal structure into human cell models for radiation biology research. The “complexDNA” tool offers a valuable resource for creating intricate DNA structures for future studies. Further refinements, such as implementing smaller voxels for euchromatin regions, are proposed to enhance the model’s accuracy.

Low-dose radiation research insights in experimental animals: A gateway to therapeutic implications

In recent years, a significant research effort has been underway to explore the effects of low-dose radiation (LDR). Animal models play a key role in various fields of research, including biomedicine, pharmaceutical, environmental, and behavioral studies. The use of animal models has been an invaluable tool in radiation research for understanding radiation biology, assessing radiation risks, and developing strategies for radiation protection and medical management. In the present review, the initial part focuses on the deleterious effects of high-dose radiation, and in correlation to that, in the later part of the review, the emphasis has been given to experimental approaches to explore the beneficial effects of LDR using animal models. This review could help explore the innovative approach for future research targeting the therapeutic role of LDR in various diseases, including depression, Cancer, Parkinson’s disease, and Alzheimer’s disease. Keywords: animal model, high dose radiation, low dose radiation, mice, rat.

Liquid water radiolysis induced by secondary electrons generated from MeV-energy carbon ions.

Fast ion beams induce damage to deoxyribonucleic acid (DNA) by chemical products, including secondary electrons, produced from interaction with liquid water in living cells. However, the production process of these chemical products in the Bragg peak region used in particle therapy is not fully understood. To investigate this process, we conducted experiments to evaluate the radiolytic yields produced when a liquid water jet in vacuum is irradiated with MeV-energy carbon beams. We used secondary ion mass spectrometry to measure the products, such as hydronium cations (H3O+) and hydroxyl anions (OH-), produced along with ·OH radicals, which are significant inducers of DNA damage formation. In addition, we simulated the ionization process in liquid water by incident ions and secondary electrons using a Monte Carlo code for radiation transport. Our results showed that secondary electrons, rather than incident ions, are the primary cause of ionization in water. We found that the production yield of H3O+ or OH- was linked to the frequency of ionization by secondary electrons in water, with these electrons having energies between 10.9 and 550eV. These electrons are responsible for ionizing the outer-shell electrons of water molecules. Finally, we present that the elementary processes contribute to advancing radiation biophysics and biochemistry, which study the formation mechanism of DNA damage.

Computer modeling of a new type galactic cosmic rays simulator

A new type of a galactic cosmic rays (GCR) simulator, provided at the JINR Laboratory of Radiation Biology, is potentially capable of generating a complex radiation field with inclusions of a variety of ions with a wide energy range and with required abundance at the charged particle accelerators. This complex multicomponent radiation field simulates radiation environment inside a spacecraft during an interplanetary flight, for example, to Mars. The article provides an analytical description of the GCR simulator as well as a description of a specially developed software that enables selection of necessary parameters of a simulator model for creating relevant mixed radiation conditions. The software implements processing of data obtained with Monte Carlo-based FLUKA and PHITS programs, fitting and optimization of model parameters as well as data visualization tools.

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Given that the original tumor microenvironment of oral cancer cannot be reproduced, predicting the therapeutic effects of irradiation using monolayer cultures and animal models of ectopic tumors is challenging. Unique properties of carbon-ion irradiation (CIR) characterized by the Bragg peak exert therapeutic effects on tumors and prevent adverse events in surrounding normal tissues. However, the underlying mechanism remains unclear. The biological effects of CIR were evaluated on three-dimensional (3D) in vitro models of normal oral mucosa (NOMM) and oral cancer (OCM3 and OCM4) consisting of HSC-3 and HSC-4 cells. A single 10- or 20-Gy dose of CIR was delivered to NOMM, OCM3, and OCM4 models. Histopathological and histomorphometric analyses and labeling indices for Ki-67, γH2AX, and TUNEL were examined after CIR. The concentrations of high mobility group box 1 (HMGB1) were measured. NOMM exhibited epithelial thinning after CIR, which could be caused by the decreased presence of Ki-67-labeled basal cells. The relative proportion of the thickness of cancer cells to the underlying stroma in cancer models decreased after CIR. This finding appeared to be supported by changes in the three labeling indices, indicating CIR-induced cancer cell death, mostly via apoptosis. Furthermore, the three indices and the HMGB1 release levels significantly differed among the OCM4 that received different doses and with different incubation times after CIR while those of the OCM3 models did not, suggesting more radiosensitivity in the OCM4. The three 3D in vitro models can be a feasible and novel tool to elucidate radiation biology.

Early and Late Effects of Low-Dose X-ray Exposure in Human Fibroblasts: DNA Repair Foci, Proliferation, Autophagy, and Senescence.

The effects of low-dose radiation exposure remain a controversial topic in radiation biology. This study compares early (0.5, 4, 24, 48, and 72 h) and late (5, 10, and 15 cell passages) post-irradiation changes in γH2AX, 53BP1, pATM, and p-p53 (Ser-15) foci, proliferation, autophagy, and senescence in primary fibroblasts exposed to 100 and 2000 mGy X-ray radiation. The results show that exposure to 100 mGy significantly increased γH2AX, 53BP1, and pATM foci only at 0.5 and 4 h post irradiation. There were no changes in p-p53 (Ser-15) foci, proliferation, autophagy, or senescence up to 15 passages post irradiation at the low dose.

Investigating the Radiobiological Response to Peptide Receptor Radionuclide Therapy Using Patient-Derived Meningioma Spheroids.

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of 177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT.

The Central Role of Cytogenetics in Radiation Biology.

Radiation cytogenetics has a rich history seldom appreciated by those outside the field. Early radiobiology was dominated by physics and biophysical concepts that borrowed heavily from the study of radiation-induced chromosome aberrations. From such studies, quantitative relationships between biological effect and changes in absorbed dose, dose rate and ionization density were codified into key concepts of radiobiological theory that have persisted for nearly a century. This review aims to provide a historical perspective of some of these concepts, including evidence supporting the contention that chromosome aberrations underlie development of many, if not most, of the biological effects of concern for humans exposed to ionizing radiations including cancer induction, on the one hand, and tumor eradication on the other. The significance of discoveries originating from these studies has widened and extended far beyond their original scope. Chromosome structural rearrangements viewed in mitotic cells were first attributed to the production of breaks by the radiations during interphase, followed by the rejoining or mis-rejoining among ends of other nearby breaks. These relatively modest beginnings eventually led to the discovery and characterization of DNA repair of double-strand breaks by non-homologous end joining, whose importance to various biological processes is now widely appreciated. Two examples, among many, are V(D)J recombination and speciation. Rapid technological advancements in cytogenetics, the burgeoning fields of molecular radiobiology and third-generation sequencing served as a point of confluence between the old and new. As a result, the emergent field of "cytogenomics" now becomes uniquely positioned for the purpose of more fully understanding mechanisms underlying the biological effects of ionizing radiation exposure.

Dose Rate Effects from the 1950s through to the Era of FLASH.

Numerous dose rate effects have been described over the past 6-7 decades in the radiation biology and radiation oncology literature depending on the dose rate range being discussed. This review focuses on the impact and understanding of altering dose rates in the context of radiation therapy, but does not discuss dose rate effects as relevant to radiation protection. The review starts with a short historic review of early studies on dose rate effects, considers mechanisms thought to underlie dose rate dependencies, then discusses some current issues in clinical findings with altered dose rates, the importance of dose rate in brachytherapy, and the current timely topic of the use of very high dose rates, so-called FLASH radiotherapy. The discussion includes dose rate effects in vitro in cultured cells, in invivo experimental systems and in the clinic, including both tumors and normal tissues. Gaps in understanding dose rate effects are identified, as are opportunities for improving clinical use of dose rate modulation.

Mechanisms Underlying the Development of Murine T-Cell Lymphoblastic Lymphoma/Leukemia Induced by Total-Body Irradiation.

Exposure to ionizing radiation is associated with an increased risk of hematologic malignancies in myeloid and lymphoid lineages in humans and experimental mice. Given that substantial evidence links radiation exposure with the risk of hematologic malignancies, it is imperative to deeply understand the mechanisms underlying cellular and molecular changes during the latency period between radiation exposure and the emergence of fully transformed malignant cells. One experimental model widely used in the field of radiation and cancer biology to study hematologic malignancies induced by radiation exposure is mouse models of radiation-induced thymic lymphoma. Murine radiation-induced thymic lymphoma is primarily driven by aberrant activation of Notch signaling, which occurs frequently in human precursor T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (T-ALL). Here, we summarize the literature elucidating cell-autonomous and non-cell-autonomous mechanisms underlying cancer initiation, progression, and malignant transformation in the thymus following total-body irradiation (TBI) in mice.

Organization and operation of multi particle therapy facilities: the Marburg Ion-Beam Therapy Center, Germany (MIT)

PurposeThe Marburg Ion-Beam Therapy Center (MIT) is one of two particle therapy centers in Germany that enables the treatment of patients with both protons and carbon ions. The facility was build by Siemens Healthineers and is one of only two centers worldwide built by Siemens (Marburg, Germany and Shanghai, China). The present report provides an overview of technical and clinical operations as well as research activities at MIT.MethodsThe MIT was completed in 2011 and uses a synchrotron for accelerating protons and carbon ions up to energies of 250 MeV/u and 430 MeV/u respectively. Three treatment rooms with a fixed horizontal beam-line and one room with a 45 degree beam angle are available.ResultsSince the start of clinical operations in 2015, around 2.500 patients have been treated at MIT, about 40% with carbon ions and 60% with protons. Currently around 400 patients are treated each year. The majority of the patients suffered from benign and malign CNS tumors (around 40%) followed by head and neck tumors (around 23%). MIT is actively involved in clinical studies with its patients. In addition to clinical operations, there is active research at MIT in the fields of radiation biology and medical physics. The focus is on translational research to improve the treatment of H & N carcinomas and lung cancer (NSCLC). Moreover, intensive work is being carried out on the technical implementation of FLASH irradiation for research purposes.ConclusionThe MIT is one of two centers worldwide that were built by Siemens Healtineers and has been successfully in clinical operation since 2015. The service provided by Siemens is guaranteed until 2030, the future after 2030 is currently under discussion.

Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Density estimation via measure transport: Outlook for applications in the biological sciences

AbstractOne among several advantages of measure transport methods is that they allow or a unified framework for processing and analysis of data distributed according to a wide class of probability measures. Within this context, we present results from computational studies aimed at assessing the potential of measure transport techniques, specifically, the use of triangular transport maps, as part of a workflow intended to support research in the biological sciences. Scenarios characterized by the availability of limited amount of sample data, which are common in domains such as radiation biology, are of particular interest. We find that when estimating a distribution density function given limited amount of sample data, adaptive transport maps are advantageous. In particular, statistics gathered from computing series of adaptive transport maps, trained on a series of randomly chosen subsets of the set of available data samples, leads to uncovering information hidden in the data. As a result, in the radiation biology application considered here, this approach provides a tool for generating hypotheses about gene relationships and their dynamics under radiation exposure.

Commissioning and Assessment of Radiation Field and Dose Inhomogeneity for a Dual X-ray Tube Cabinet Irradiator: To Ensure Accurate Dosimetry in Radiation Biology Experiments

PurposeStandardization of X-ray cabinet irradiators dose, geometry, and calibration reporting is an ongoing process. Multi-tube designs have been introduced onto the pre-clinical market and give a theoretical benefit but have not been widely assessed for use in pre-clinical irradiation conditions. The aim of this study was to report on our experience commissioning a dual x-ray source cabinet irradiator (CIXD, Xstrahl Limited, United Kingdom) and assess the dose distribution for various experimental conditions. Materials and MethodsHalf-value layer (HVL) measurement, profile measurements, and output calibration were performed with a calibrated ion chamber. Constancy measurements were performed twice daily over two weeks to assess output fluctuations. Film measurements were completed using solid water to assess percent depth dose and homogeneity within the field and within variable thickness of solid water and phosphate-buffered saline (PBS) solution. Film measurements were repeated for various arrangements of petri dishes filled with PBS or water and in a 3D printed mouse phantom. ResultsThe X-ray tubes measured in-air output was 1.27 Gy/min. The HVL was 1.7 mm Cu. The upper and lower tubes both exhibited the heel effect, but when operated simultaneously the effect was reduced. Ion chamber measurements revealed 15% dose inhomogeneity within the tray area (18 × 18 cm2). Film measurements in the petri dishes indicated minor non-uniformities with the arrangements of experimental apparatus. The mouse phantom with film agreed with ion chamber measurements for various phantom placement and orientations. ConclusionX-ray cell culture irradiation with the dual tube cabinet irradiation is efficient and robust when utilizing established dosimetric tools to confirm output and homogeneity. The conditions assumed for calibrations are often not maintained during experiments. We have confirmed that inhomogeneities are present for single tube use, however they are reduced with simultaneous tube use. Additional dosimetric monitoring should be performed for each unique irradiation setup.

Primary study of the relative and compound biological effectiveness model for boron neutron capture therapy based on nanodosimetry.

The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS-nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and β, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter effectively captures the fluctuations in model coefficients α and RBE. Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning.

RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy.

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.

Highlighting the NIAID Radiation and Nuclear Countermeasures Program's Commitment to Training and Diversifying the Radiation Workforce.

Developing and maintaining a robust and diverse scientific workforce is crucial to advance knowledge, drive innovation, and tackle societal issues that impact the economy and human health. The shortage of trained professionals in radiation and nuclear sciences derives from many factors, such as scarcity of specialized coursework, programming, professional development, and experiential learning at educational institutions, which significantly disrupt the training pipeline. Other challenges include small numbers of faculty and educators with specialized radiation/nuclear expertise that are continually overextended professionally and scientifically, with the burden of training falling on this subset of individuals. Even more alarming is the recent loss of radiobiologists due to increased retirements and deaths, leaving the radiobiology community with a void of mentors and knowledge. Lastly, inconsistency in acquiring stable grant funding to recruit and retain scientists is a major hurdle to training the next generation of radiation and nuclear scientists. Recommendations from the scientific community and the National Academies of Sciences, Engineering, and Medicine describe the need to bolster educational resources and provide more hands-on training experiences. Of equal importance was the suggestion that funding agencies provide more opportunities for training and tracking the radiation workforce. The Radiation and Nuclear Countermeasures Program (RNCP), and the Office of Research Training and Special Programs (ORTSP), both within the National Institute of Allergy and Infectious Diseases (NIAID) are committed to helping to develop and sustain the radiation research workforce. This commentary illustrates the importance of addressing radiation workforce development and outlines steps that the RNCP is taking to help mitigate the issue. In addition, the role for Diversity, Equity, Inclusion, and Accessibility (DEIA) in helping to increase the number of students trained in the radiation sciences is discussed, and the NIH's DEIA priorities and RNCP efforts to improve DEIA in the research community are highlighted. One of the main goals of this commentary is to provide awareness of available educational (i.e., development of a radiation biologist eBook) and funding resources. A summary of available awards targeting early- to mid-stage investigators and diversity candidates is given, and it is hoped that this list, although not exhaustive and not specific for all focus areas in radiation (e.g., cancer research), will encourage more radiation biologists to explore and apply to these under-utilized opportunities.

High Separation Factor, High Molar Activity, and Inexpensive Purification Method for the Production of Pure 165Er.

Introduction: Auger electron-emitting radionuclides with low (0.001-1 keV) energy, short-range (2-500 nm), and high linear energy transfer (4-26 keV/μm) can play an important role in the targeted radionuclide therapy (TRT) of cancer. 165Er is a pure Auger electron-emitting radionuclide, making it a useful tool for the fundamental studies of the biological effects of Auger electrons. This work develops a simple, inexpensive, high separation factor, and high molar activity radiochemical isolation process for the production of 165Er (t1/2 10.36 h) suitable for TRT in vitro and in vivo studies using irradiated natHo solid targets. Methods: Small medical cyclotron proton-irradiation of natHo targets produced 165Er in GBq scale quantities. 165Er was isolated using cation exchange chromatographic resin (AG 50W-X8, 200-400 mesh, 20 mL, under atmospheric pressure) using α-hydroxyisobutyric acid (70 mM, pH 4.75) followed by extraction using TK212, TK211, and TK221 extraction chromatographic columns. Radio nuclidic and chemical purity of the final 165Er were confirmed using HPGe Gamma spectrometry and induction coupled plasma-mass spectrometry analysis, respectively. The purified 165Er was radiolabeled with two radiometal chelators (DOTA and Crown) and used to produce a new Auger electron-emitting radiopharmaceutical, [165Er]Er-Crown-TATE. Results: Irradiation of 200 mg natHo targets with 20-30 μA of 12.8 MeV protons produced 165Er at 25 ± 5 MBq·μA-1·h-1. The 4.5 ± 0.5 h radiochemical isolation yielded GBq scale of 165Er in 0.05 M HCl (2 mL) with a radiochemical yield of 78.0 ± 5.6% decay corrected to the end of bombardment (EoB) and a Ho/165Er separation factor of (1.14 ± 0.25) × 106. The product showed high radio nuclidic purity and chemical purity. Concentration-dependent radiolabeling experiments with Crown and DOTA were performed resulting in the successful labeling of 165Er with high (>90%) radiochemical yield. Radiolabeling experiments with Crown-TATE were performed 8 h after EoB and synthesized [165Er]Er-Crown-TATE at molar activities of 202.4 MBq·nmol-1 at the end of synthesis (EoS). Conclusions: A 3 h cyclotron irradiation and 4.5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutic effects of Auger electron emissions. This will enable future fundamental radiation biology experiments of pure Auger electron-emitting therapeutic radiopharmaceuticals, such as [165Er]Er-Crown-TATE, which will be used to understand the impact of Auger electrons in TRT.

Evaluation of ChatGPT's Real-Life Implementation in Undergraduate Dental Education: Mixed Methods Study.

The recent artificial intelligence tool ChatGPT seems to offer a range of benefits in academic education while also raising concerns. Relevant literature encompasses issues of plagiarism and academic dishonesty, as well as pedagogy and educational affordances; yet, no real-life implementation of ChatGPT in the educational process has been reported to our knowledge so far. This mixed methods study aimed to evaluate the implementation of ChatGPT in the educational process, both quantitatively and qualitatively. In March 2023, a total of 77 second-year dental students of the European University Cyprus were divided into 2 groups and asked to compose a learning assignment on "Radiation Biology and Radiation Protection in the Dental Office," working collaboratively in small subgroups, as part of the educational semester program of the Dentomaxillofacial Radiology module. Careful planning ensured a seamless integration of ChatGPT, addressing potential challenges. One group searched the internet for scientific resources to perform the task and the other group used ChatGPT for this purpose. Both groups developed a PowerPoint (Microsoft Corp) presentation based on their research and presented it in class. The ChatGPT group students additionally registered all interactions with the language model during the prompting process and evaluated the final outcome; they also answered an open-ended evaluation questionnaire, including questions on their learning experience. Finally, all students undertook a knowledge examination on the topic, and the grades between the 2 groups were compared statistically, whereas the free-text comments of the questionnaires were thematically analyzed. Out of the 77 students, 39 were assigned to the ChatGPT group and 38 to the literature research group. Seventy students undertook the multiple choice question knowledge examination, and examination grades ranged from 5 to 10 on the 0-10 grading scale. The Mann-Whitney U test showed that students of the ChatGPT group performed significantly better (P=.045) than students of the literature research group. The evaluation questionnaires revealed the benefits (human-like interface, immediate response, and wide knowledge base), the limitations (need for rephrasing the prompts to get a relevant answer, general content, false citations, and incapability to provide images or videos), and the prospects (in education, clinical practice, continuing education, and research) of ChatGPT. Students using ChatGPT for their learning assignments performed significantly better in the knowledge examination than their fellow students who used the literature research methodology. Students adapted quickly to the technological environment of the language model, recognized its opportunities and limitations, and used it creatively and efficiently. Implications for practice: the study underscores the adaptability of students to technological innovations including ChatGPT and its potential to enhance educational outcomes. Educators should consider integrating ChatGPT into curriculum design; awareness programs are warranted to educate both students and educators about the limitations of ChatGPT, encouraging critical engagement and responsible use.