The assessment and management of risks associated with exposures to short-range Auger- and beta-emitting radionuclides. State of the art and proposals for lines of research

Abstract

The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk.Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly.The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides.

Calculation of cellular S-values using Geant4-DNA: The effect of cell geometry

“…I-125 was chosen as the most studied radionuclide and In-111 is being considered in clinical studies (phase I) in the form of In-111-BLMC (bleomycin) (Cornelissen and Vallis, 2010). Although Tc-99m is the most widely used diagnostic radionuclide, concerns have been raised regarding the consequences of highly localized energy deposition of its Auger electrons, which could exacerbate the radiotoxic response at the cellular level (Paquet et al, 2013).…”

Inelastic Cross Sections for Low-Energy Electrons in Liquid Water: Exchange and Correlation Effects

“…Low-energy electrons are particularly important in radiation effects studies since they represent the so-called ''track-ends'', which are associated with increased radiobiological effectiveness (4,5). Moreover, owing to their small range, they often lead to a heterogeneous dose distribution at the (sub) cellular level, therefore, complicating risk assessment efforts (6). Studies on low-energy electron interactions in condensed biomaterials (especially liquid water and DNA) are an important prerequisite for understanding radiation action in cells by almost any ionizing radiation field (7,8) while also providing the physical basis of novel therapeutic modalities based on targeted radionuclide therapy with Auger emitters (9)(10)(11) and nanoparticle-enhanced radiotherapy (12)(13)(14).…”

Hto, Tritiated Amino Acid Exposure and External Exposure Induce Differential Effects on Hematopoiesis and Iron Metabolism

“…However, at the micro-dosimetric level concentrated energy deposition can occur – particularly following the incorporation of OBT into structural components of cells and tissues. Such concentrations could result in higher than expected risks 14,15 . To study this, more evenly distributed, gamma-rays from cobalt-60 were employed at the same doses and dose rates for comparison.…”

“…OBT forms are able to be incorporated within the cell and its nucleus, resulting in a higher probability of lethal damage to the cell 11–13 . It is therefore speculated that risks associated with tritium internal exposures may be underestimated 14,15 .…”