Biological and internal dosimetry for radiation medicine: current status and future perspectives.

The International Atomic Energy Agency (IAEA) and Hiroshima International Council for Health Care of the Radiation-Exposed (HICARE) jointly organized two relevant workshops in Hiroshima, Japan, i.e. a Training Meeting 'Biodosimetry in the 21st century' (BIODOSE-21) on 10-14 June 2013 and a Workshop on 'Biological and internal dosimetry: recent advance and clinical applications' which took place between 17 and 21 February 2020.

Clinical Applications of Biological Dosimetry in Patients Exposed to Low Dose Radiation Due to Radiological, Imaging or Nuclear Medicine Procedures.

Radiation dosimetric biomarkers have found applications beyond radiation protection area and now are actively introduced into clinical practice. Cytogenetic assays appeared to be a valuable tool for individualized quantifying radiation effects in patients, with high capability for assessing genotoxicity of various medical exposure modalities and providing meaningful radiation dose estimates for prognoses of radiation-related cancer risk. This review summarized current data on the use of biological dosimetry methods in patients undergoing various medical irradiations to low doses.

Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review.

A search for effective methods for the assessment of patients' individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT.

Radiation Exposure Biomarkers in the Practice of Medical Radiology: Cooperative Research and the Role of the International Atomic Energy Agency (IAEA) Biodosimetry/Radiobiology Laboratory.

The strategy toward personalized medicine in radiation oncology, nuclear medicine, and diagnostic and interventional radiology demands a specific set of assays for individualized estimation of radiation load for safety concerns and prognosis of normal tissue reactions caused by ionizing radiation. Apparently, it seems reasonable to use validated radiation dosimetric biomarkers for these purposes. However, a number of gaps in knowledge and methodological limitations still have to be resolved until dosimetric biomarkers will start to play a valuable role in clinical practice beyond radiation protection and radiation medicine.

Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy.

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

CLINICAL APPLICATIONS OF BIOMARKERS OF RADIATION EXPOSURE: LIMITATIONS AND POSSIBLE SOLUTIONS THROUGH COORDINATED RESEARCH.

Dosimetric biomarkers have been effectively and intensively used for a long time in the area of radiation protection. In contrast to that, no robust standards or widely accepted protocols for application of these end-points in radiotherapy, diagnostic and interventional radiology and nuclear medicine exist to date. The International Atomic Energy Agency (IAEA) organized the review of the available data on the possibilities of the use of dosimetric biomarkers in medical irradiation scenarios.

The Frequency of Lymphocytes Containing Dumbbell-Shaped Nuclei Depends on Ionizing Radiation Dose and Correlates with Appearance of Chromosomal Aberrations.

Nuclear anomalies of different types appear in cells in response to the action of ionizing radiation after the passage of the first mitotic division. In this article, we present the results of the study of the frequency of occurrence of three types of nuclear anomalies ("tailed" nuclei, nucleoplasmic bridges, and dumbbell-shaped nuclei) in human lymphocytes cultured with cytochalasin B when exposed to X-rays at doses of 0.0, 0.

Biomarkers of Ionizing Radiation Exposure: A Multiparametric Approach.

Humans are exposed to ionizing radiation not only through background radiation but also through the ubiquitous presence of devices and sources that generate radiation. With the expanded use of radiation in day-to-day life, the chances of accidents or misuse only increase. Therefore, a thorough understanding of the dynamic effects of radiation exposure on biological entities is necessary.

Non-targeted effects of ionising radiation--implications for low dose risk.

Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation.

Some important questions connected with non-targeted effects.

This paper briefly reviews the highlights of experimental evidence that led to the adoption of the term "non-targeted" to describe new effects induced by ionising radiation that did not fit the classical radiobiological paradigm, principally genomic instability and bystander effect, identifying the reports that were most influential on the subsequent course of radiobiological research. The issue of appropriate terminology for the new effects is discussed. Particular emphasis is placed on the inheritance of genomic instability, where there are issues concerning which effects should be considered as transgenerational.

A (238)Pu irradiator for exposure of cultured cells with alpha-radiation: construction, calibration and dosimetry.

An alpha-particle irradiator that can facilitate investigations of alpha-radiation effects on human cells in radiation protection, carcinogenesis and radioimmunotherapy was constructed. The irradiator was based on a 1.3 GBq (238)Pu source, housed in a stainless steel tube flushed with helium.

Microbeam studies of the bystander response.

Microbeams have undergone a renaissance since their introduction and early use in the mid 60s. Recent advances in imaging, software and beam delivery have allowed rapid technological developments in microbeams for use in a range of experimental studies. The resurgence in the use of microbeams since the mid 90s has coincided with major changes in our understanding of how radiation interacts with cells.

Design, spectrum measurements and simulations for a 238Pu alpha-particle irradiator for bystander effect and genomic instability experiments.

Design, spectrum measurements and simulations for an alpha-particle irradiator for bystander effect and genomic instability experiments are presented. Measured alpha-particle energy spectra were used to confirm the characteristics of the source of the irradiator specified by the manufacturer of the source. The spectra were measured in vacuum with a high-resolution spectrometer and simulated with an AASI Monte Carlo code.

Bystander-induced differentiation: a major response to targeted irradiation of a urothelial explant model.

A ureter primary explant technique, using porcine tissue sections was developed to study bystander effects under in vivo like conditions where dividing and differentiated cells are present. Targeted irradiations of ureter tissue fragments were performed with the Gray Cancer Institute charged particle microbeam at a single location (2 microm precision) with 10 3He2+ particles (5 MeV; LET 70 keV/microm). After irradiation the ureter tissue section was incubated for 7 days allowing explant outgrowth to be formed.

Classical radiation biology, the bystander effect and paradigms: a reply.

Although, in retrospect, it can be seen that the bystander effect and the related effect of genomic instability were observed well before they were recognized as such, they have not been able to be accommodated within the existing understanding of how radiation causes late effects, which provides the basis for radiological protection standards. It is argued here that before these effects can be fully researched and there can be full confidence in radiological protection, a paradigm shift that provides a framework in which these effects can be considered alongside the well established effects of radiation is needed. In particular this framework will encompass the epigenetic as well as genetic aspects of radiation biology.

Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away.

A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning "bystander" responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit.