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Assessment and management of risks associated with exposures to Auger- and beta-emitting radionuclides

Recommendations and proposals for lines of research, Scientific direction report 2010-03, 106 p.

Document type > *Report/contribution to WG (paper or CD-Rom)

Keywords > beta emitters, Auger emitters

Research Unit > IRSN/DS

Authors > PAQUET François, BIAU Alain, BLANCHARDON Eric, PASQUIER Jean-Luc

Publication Date > 31/03/2010

Summary

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 with well-established relevance for the management and prevention of exposures.

 

Despite this, there are a number of dissenting voices, claiming that this system is not suitable for estimating the risks resulting from internal exposures, particularly when incorporated radionuclides decay, emitting electrons. Criticisms of the system particularly pertain to Auger- and beta-emitting radionuclides, the intake of which can occur during environmental and industrial exposures or, simply, during a medical use of ionising radiation for diagnostic or therapeutic purposes.

 
These debates result from a lack of data in the fields of dosimetry and toxicology of these radionuclides. Auger and beta emitters can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to the vector with which they are associated. Given the limited range of electrons in matter, this heterogeneous distribution can generate highly localised energy depositions, not taken into account in conventional dosimetry methods, which make the assumption of uniform energy depositions.
These specific physical and biochemical features of some of these radionuclides seem to influence their cellular toxicity directly. It is thus established that intranuclear distribution of iodine-125 is more effective for the induction of mutations or even cell death than a cytosolic distribution1. This point is explained by the very short range of Auger electrons in matter (around a few dozen nm), which, in the case of an intranuclear distribution, would deliver all of their energy in the vicinity of the DNA, which, if affected, would be detrimental to the survival of the cell.
The observation of these phenomena has led some scientists to call for a revision or even the abandonment of the current radiological protection system and the creation of new concepts that would take into account the specific characteristics mentioned above.
Various other systems have been proposed, based on a dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy depositions occurring near or within the DNA molecule. The progress made in the field of modelling now makes it possible to accurately calculate these energy depositions at virtually all scales, from the molecules to the tissues overall.
However, the algorithms developed for dose calculations at the molecular level are not sufficient to claim a better assessment of the risks incurred. Favouring a microdosimetric approach for risk assessments would require comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and, above all, all of the mechanisms leading from a cellular energy deposition to the appearance of a health detriment. It has been established that the human body has developed many defence mechanisms, including the repair of damaged molecules, the replacement of killed cells, and the elimination of mutated cells. Detailed knowledge of these mechanisms for repair or, conversely, propagation and amplification of molecular damage is therefore an essential prerequisite for the use of any molecular or cellular dosimetric information for radiological protection purposes.
The required knowledge is not available today. In fact, it is not yet possible to link a cellular energy deposition to a probability of occurrence of health effects. These deficiencies have led the ICRP to choose a protection system based on the macroscopic observation of health detriments, associated with an aggregate dose of radiation rather than a mechanistic analysis at the cellular level and an incorporation of the various steps leading to the genesis of radiation-induced pathologies. This approach has recognised limitations but is intended to provide a simple system for exposure management.
The heuristic deficits of the other approaches that could be an alternative to the current radiological protection system should not discourage efforts. The radiological protection system can and should be improved in order to take into account any specific characteristics of radionuclides or certain exposure situations. Protection against exposure to Auger and beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of transmitters in various cellular structures, but also radiotoxicological studies to define the relative biological efficacy of each Auger emitter used in medicine, and certain beta emitters, whose behaviour may highly depend on their chemical form during intake.
The scientific expertise as well as the human and physical resources needed to conduct these studies have been identified and are available. They should now be mobilised in order to improve the protection of people exposed to these particular radionuclides.

 

1 A cytosolic distribution corresponds to a homogeneous deposit in the soluble portion of the cell (outside the cell organelles).


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