A semi-automated FISH-based micronucleus-centromere assay for biomonitoring of hospital workers exposed to low doses of ionizing radiation

The aim of the present study was to perform cytogenetic analysis by means of a semi-automated micronucleus-centromere assay in lymphocytes from medical radiation workers. Two groups of workers receiving the highest occupational doses were selected: 10 nuclear medicine technicians and 10 interventional radiologists/cardiologists. Centromere-negative micronucleus (MNCM-) data, obtained from these two groups of medical radiation workers were compared with those obtained in matched controls. The blood samples of the matched controls were additionally used to construct a 'low-dose' (0-100 mGy) MNCM-dose-response curve to evaluate the sensitivity and suitability of the micronucleus-centromere assay as an 'effect' biomarker in medical surveillance programs. The physical dosimetry data of the 3 years preceding the blood sampling, based on single or double dosimetry practices, were collected for the interpretation of the micronucleus data. The in vitro radiation results showed that for small sized groups, semi-automated scoring of MNCM-enables the detection of a dose of 50 mGy. The comparison of MNCM-yields in medical radiation workers and control individuals showed enhanced MNCM-scores in the medical radiation workers group (P=0.15). The highest MNCM-scores were obtained in the interventional radiologists/cardiologists group, and these scores were significantly higher compared with those obtained from the matched control group (P=0.05). The higher MNCM-scores observed in interventional radiologists/cardiologists compared with nuclear medicine technicians were not in agreement with the personal dosimetry records in both groups, which may point to the limitation of 'double dosimetry' procedures used in interventional radiology/cardiology. In conclusion, the data obtained in the present study supports the importance of cytogenetic analysis, in addition to physical dosimetry, as a routine biomonitoring method in medical radiation workers receiving the highest occupational radiation burdens

RBE, reference RBE and clinical RBE: applications of these concepts in hadron therapy.

Introduction of heavy particles (hadrons) into radiation therapy aims at improving the physical selectivity of the irradiation (e.g. proton beams), or the radiobiological differential effect (e.g. fast neutrons), or both (e.g. heavy-ion beams). Each of these new therapy modalities requires several types of information before prescribing safely the doses to patients, as well as for recording and reporting the treatments: (i) absorbed dose measured in a homogeneous phantom in reference conditions; (ii) dose distribution computed at the level of the target volume(s) and the normal tissues at risk; (iii) radiation quality from which a RBE evaluation could be predicted and (iv) RBE measured on biological systems or derived from clinical observation. In hadron therapy, the RBE of the different beams raises specific problems. For fast neutrons, the RBE varies within wide limits (about 2 to 5) depending on the neutron energy spectrum, dose, and biological system. For protons, the RBE values range between smaller limits (about 1.0 to 1.2). A clinical benefit can thus not be expected from RBE differences. However, the proton RBE problem cannot be ignored since dose differences of about 5% can be detected clinically in some cases. The situation is most complex with heavy ions since RBE variations are at least as large as for fast neutrons, as a function of particle type and energy, dose and biological system. In addition, RBE varies with depth. Radiation quality thus has to be taken into account when prescribing and reporting a treatment. This can be done in different ways: (a) description of the method of beam production; (b) computed LET spectra and/or measured microdosimetric spectra at the points clinically relevant; (c) RBE determination. The most relevant RBE data are those obtained for late tolerance of normal tissues at 2 Gy per fraction ("reference RBE"). The "clinical RBE" selected by the radiation oncologist when prescribing the treatment will be close to the reference RBE, but other factors (such as heterogeneity in dose distribution) may influence the selection of the clinical RBE. Combination of microdosimetric data and experimental RBE values improves the confidence in both sets of data

Contribution of Microdosimetry To the Specification of Neutron Beam Quality for the Choice of the Clinical Rbe in Fast-neutron Therapy

This paper discusses the Relative Biological Effectiveness (RBE) problem in neutron therapy and the way it is handled today. The possible contribution of microdosimetry to improve the situation is suggested. In high LET radiation therapy, radiation quality and radiation quality differences have to be taken into account and specified. In fast neutron therapy, an operational approach has been adopted which is based on the concept of 'clinical RBE'. The paper discusses the quantities of RBE, reference RBE and clinical RBE, their relationship and significance in radiation therapy. In particular, the difference between the well-defined RBE in radiation biology and the clinical RBE which is based on the judgement of radiotherapists are elucidated and emphasised. Although it is based first on the reference RBE, the clinical RBE implicitly includes differences in physical selectivity of the irradiation beam as well as clinical experience when available. Microdosimetry can provide useful information for the selection of the clinical RBE by giving a description of the radiation quality at the point of interest. A method has been developed, using iterative and deconvolution techniques, allowing the derivation of the RBE of a given new neutron beam provided the microdosimetric spectra are available. This method has been tested by combining microdosimetric data and radiobiological data (intestinal crypt cell regeneration) obtained at nine neutron therapy beams. For a 'new' neutron beam, the RBE value computed on the basis of the microdosimetric spectra would have the same accuracy (and confidence) as RBE values measured directly. Radiobiological data, systematically obtained for late normal tissue tolerance at 2 Gy per fraction, are still missing; their correlation with the microdosimetric data would be most relevant for clinical applications

Contribution à l'étude de l'efficacité biologique relative des faisceaux de photons et d'électrons de 20 MeV du betatron

Thèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 196