Biomedical subjects

H Thierens

Publications and source records attributed to H Thierens.

At least 19 recordsLinked to original sources

PubMed2005

Experimental verification of lung dose with radiochromic film: comparison with Monte Carlo simulations and commercially available treatment planning systems.

The purpose of this study was to assess the absorbed dose in and around lung tissue by performing radiochromic film measurements, Monte Carlo simulations and calculations with superposition convolution algorithms. We considered a layered polystyrene phantom of 12 x 12 x 12 cm3 containing a central cavity of 6 x 6 x 6 cm3 filled with Gammex RMI lung-equivalent material. Two field configurations were investigated, a small 1 x 10 cm2 field and a larger 10 x 10 cm2 field. First, we performed Monte Carlo simulations to investigate the influence of radiochromic film itself on the measured dose distribution when the film intersects a lung-equivalent region and is oriented parallel to the central beam axis. To that end, the film and the lung-equivalent materials were modelled in detail, taking into account their specific composition. Next, measurements were performed with the film oriented both parallel and perpendicular to the central beam axis to verify the results of our Monte Carlo simulations. Finally, we digitized the phantom in two commercially available treatment planning systems, Helax-TMS version 6.1A and Pinnacle version 6.2b, and calculated the absorbed dose in the phantom with their incorporated superposition convolution algorithms to compare with the Monte Carlo simulations. Comparing Monte Carlo simulations with measurements reveals that radiochromic film is a reliable dosimeter in and around lung-equivalent regions when the film is positioned perpendicular to the central beam axis. Radiochromic film is also able to predict the absorbed dose accurately when the film is positioned parallel to the central beam axis through the lung-equivalent region. However, attention must be paid when the film is not positioned along the central beam axis, in which case the film gradually attenuates the beam and decreases the dose measured behind the cavity. This underdosage disappears by offsetting the film a few centimetres. We find deviations of about 3.6% between Monte Carlo and the superposition convolution algorithm of Pinnacle behind the lung region, for both field configurations. Pinnacle is quite accurate in the lung region. Deviations up to 5.6% for the small field are found in the lung region between Monte Carlo and the superposition convolution algorithm of Helax-TMS. Behind the lung region, Helax-TMS is in better agreement with Monte Carlo. Radiochromic film measurements or Monte Carlo simulations are reliable methods to establish the dose in and around lung tissue.

Algorithms↗

PubMed2005

Cytogenetic biodosimetry of an accidental exposure of a radiological worker using multiple assays.

A technician involved in the maintenance of X-ray equipment visited the occupational medicine service with complaints of skin lesions, apparently caused by an accidental exposure three months earlier. To estimate the dose received by the technician in the accident, biodosimetry was performed 6 and 18 months post-exposure with the dicentric and micronucleus assays. Part of the latest blood sample was also used for retrospective dosimetry by fluorescence in situ hybridisation (FISH) analysis for translocations. The data obtained 6 and 18 months post-exposure indicate that both dicentrics and micronuclei disappear with a half-time of 1 y. After correction for delayed blood sampling, dose values of 0.75 Gy (95% confidence limits 0.56-1.05 Gy) from dicentrics and 0.96 Gy (95% confidence limits 0.79-1.18 Gy) from micronuclei were obtained. FISH analysis of translocations resulted in a dose estimate of 0.79 Gy (95% confidence limits 0.61-0.99 Gy). The satisfactory agreement between the three cytogenetic endpoints supports the use of the micronucleus assay for triage purposes in the case of large scale radiological accidents and provides further evidence for the valid use of FISH for translocations as a reliable retrospective biological dosimeter.

Adult↗

PubMed2005

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations.

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

Dose-Response Relationship, Radiation↗

PubMed2004

Optimised tracer-dependent dosage cards to obtain weight-independent effective doses.

PURPOSE: The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to determine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. METHODS: Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiopharmaceuticals were investigated using cluster analysis. RESULTS: Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA=7, nB=76, nC=12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodine-labelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. CONCLUSION: Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses.

Adult↗

PubMed2004

DOSSCORE: an accelerated DOSXYZnrc code with an efficient stepping algorithm and scoring grid.

DOSSCORE is an accelerated version of DOSXYZnrc that allows photons to cross voxel boundaries of the same medium and utilizes a separate scoring grid superimposed on the geometrical grid. Two different stepping algorithms, the hownear method and the scaling method are implemented in DOSSCORE. The hownear method allows particles to travel larger distances in homogeneous regions where there is no interest in the dose deposition of these particles, whilst the scaling method utilizes a stepping algorithm in which particles are only slowed down by the boundaries of the geometrical voxels and not by the boundaries of the scoring voxels. For CT-based phantoms, only photon ray tracing is applied, which results in a rather modest speed gain of factor 1.2 compared to DOSXYZnrc. The hownear method and scaling method do not increase the speed for CT-based phantoms, but only for homogeneous phantoms and phantoms with a limited number of small heterogeneities. In cases where a small number of scoring voxels are needed, the hownear method performs better than the scaling method, whilst the opposite is true for cases when many scoring voxels are needed. The photon transport is accelerated by almost a factor of 2 for all phantoms (homogeneous, heterogeneous with much homogeneity and CT-based phantoms) compared to DOSXYZnrc. For a small number of scoring voxels, the hownear method is up to a factor of 2.6 and 1.9 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2.4 is obtained. For a full scoring grid like the one used in DOSXYZnrc, the scaling method is up to a factor of 2.2 and 1.7 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2 is obtained. A speed increase without biasing the results is very relevant. The use of two separate grids, the more efficient stepping algorithms and the accelerated photon transport can be applied to every EGS-based or other Monte Carlo code.

Algorithms↗

PubMed2004

MCDE: a new Monte Carlo dose engine for IMRT.

A new accurate Monte Carlo code for IMRT dose computations, MCDE (Monte Carlo dose engine), is introduced. MCDE is based on BEAMnrc/DOSXYZnrc and consequently the accurate EGSnrc electron transport. DOSXYZnrc is reprogrammed as a component module for BEAMnrc. In this way both codes are interconnected elegantly, while maintaining the BEAM structure and only minimal changes to BEAMnrc.mortran are necessary. The treatment head of the Elekta SLiplus linear accelerator is modelled in detail. CT grids consisting of up to 200 slices of 512 x 512 voxels can be introduced and up to 100 beams can be handled simultaneously. The beams and CT data are imported from the treatment planning system GRATIS via a DICOM interface. To enable the handling of up to 50 x 10(6) voxels the system was programmed in Fortran95 to enable dynamic memory management. All region-dependent arrays (dose, statistics, transport arrays) were redefined. A scoring grid was introduced and superimposed on the geometry grid, to be able to limit the number of scoring voxels. The whole system uses approximately 200 MB of RAM and runs on a PC cluster consisting of 38 1.0 GHz processors. A set of in-house made scripts handle the parallellization and the centralization of the Monte Carlo calculations on a server. As an illustration of MCDE, a clinical example is discussed and compared with collapsed cone convolution calculations. At present, the system is still rather slow and is intended to be a tool for reliable verification of IMRT treatment planning in the case of the presence of tissue inhomogeneities such as air cavities.

Adenocarcinoma↗

PubMed2004

Chromosomal aberrations and in vitro radiosensitivity: intra-individual versus inter-individual variability.

In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co gamma-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co gamma-rays in the G2 phase of the cell cycle. For 14 donors, 2-15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population. Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual radiosensitivity or cancer susceptibility the assays are very valuable to examine population radiosensitivity and the relationship between radiosensitivity, cancer predisposition and genotype.

Adult↗

PubMed2004

Chromosomal radiosensitivity in BRCA1 and BRCA2 mutation carriers.

PURPOSE: The chromosomal radiosensitivity of a selected group of familial breast cancer patients carrying a mutation in BRCA1 (n=11) or BRCA2 (n=9) and a group of healthy mutation carriers (n=12) was investigated and compared to a reference group of breast cancer patients without a BRCA1/2 mutation (n=78) and a group of healthy women carrying no mutation (n=58). MATERIALS AND METHODS: The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus (MN)-assay on fresh blood samples and on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. For the MN-assay, lymphocytes were exposed in vitro to 3.5 Gy and 2 Gy 60Co gamma-rays at a high dose rate (HDR) or low dose rate (LDR). 70-h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. For the G2-assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy 60Co gamma-rays after 71h incubation. Cultures were arrested 90 min after irradiation and chromatid breaks were scored in 50 metaphases. RESULTS: The group of breast cancer patients with a BRCA1 or 2 mutation was on average more radiosensitive than the control group, but not different from breast cancer patients without a BRCA mutation. The radiation response of healthy BRCA1/2 carriers was not significantly different from the control group and also not different from relatives without a BRCA mutation. Comparing the radiation response in EBV cell lines derived from breast cancer patients with or without a BRCA1 mutation revealed no significant difference. CONCLUSIONS: Our results reveal that chromosomal radiosensitivity observed in breast cancer patients heterozygous for BRCA1 or 2 mutations, could not be demonstrated in healthy BRCA1/2 mutation carriers. This suggests that mutations in BRCA1 or 2 genes are not playing a main role in chromosomal radiosensitivity, this although BRCA1 and 2 are both involved in DNA repair/signalling processes.

BRCA1 Protein↗

PubMed2004

The use of EBV-transformed cell lines of breast cancer patients to measure chromosomal radiosensitivity.

To investigate the chromosomal radiosensitivity of lymphocytes in cancer patients the micronucleus (MN) assay is often used and performed on freshly drawn peripheral blood lymphocytes. The use of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines may have a lot of advantages (e.g. large pool of cells) compared with fresh blood samples. In this study we have investigated whether the response of EBV-transformed lymphoblastoid cell lines to irradiation in the G1/S/G2 phases of the cell cycle is the same as in concordant whole blood cultures where primary lymphocytes were irradiated in the G0 phase of the cell cycle. For this study the MN assay (2 Gy) was performed on EBV-transformed cell lines of breast cancer patients and a group of healthy women. Those breast cancer patients were selected who showed an elevated chromosomal radiosensitivity in fresh blood samples in a previous study. The results demonstrated that the enhanced chromosomal radiosensitivity observed in fresh blood cultures of breast cancer patients is not present in EBV-transformed cell lines derived from the same blood samples. Therefore, care must be taken when EBV cell lines are used to assess chromosomal radiosensitivity in breast cancer patients.

Breast Neoplasms↗

PubMed2004

The use of IL-2 cultures to measure chromosomal radiosensitivity in breast cancer patients.

Enhanced chromosomal radiosensitivity in breast cancer patients has been demonstrated in several studies. To investigate the chromosomal radiosensitivity of lymphocytes in breast cancer patients the G2 and micronucleus (MN) assays are often used. In these assays blood samples are exposed to ionizing radiation and the number of radiation-induced micronuclei or chromatid breaks are scored. In most studies investigating the in vitro chromosomal radiosensitivity of breast cancer patients the G2 and MN assays were performed on freshly drawn blood. The disadvantage of working with fresh blood samples is that in most cases only one blood sample can be obtained and that the assay cannot be easily repeated without further blood sampling. To allow repeated testing we propose the use of long-term cultures of T lymphocytes (IL-2 cultures). In this study we therefore investigated whether the radiation-induced MN response in IL-2 cultures was the same as in concordant whole blood cultures. For this study the MN assay (2 Gy) was performed on IL-2 cultures of 11 sensitive breast cancer patients and 20 healthy women. The results demonstrate that the enhanced chromosomal radiosensitivity observed in whole blood cultures of breast cancer patients is not present in IL-2 cultures derived from the same blood samples. Therefore, care has to be taken when IL-2 cultures are used to assess chromosomal radiosensitivity in breast cancer patients.

Blood Cells↗

PubMed2004

Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.

Antineoplastic Agents↗

PubMed2003

The value of radiochromic film dosimetry around air cavities: experimental results and Monte Carlo simulations.

In this study we investigate radiochromic film dosimetry around air cavities with particular focus on the perturbation of the dose distribution by the film when the film is parallel to the beam axis. We considered a layered polystyrene phantom containing an air cavity as a model for the air-soft tissue geometry that may occur after surgical resection of a paranasal sinus tumour. A radiochromic film type MD-55 was positioned within the phantom so that it intersected the cavity. Two phantom set-ups were examined. In the first case, the air cavity is at the centre of the phantom, thus the film is lying along the central beam axis. In the second case, the cavity and film are located 2 cm offset from the phantom centre and the central beam axis. In order to examine the influence of the film on the dose distribution and to interpret the film-measured results, Monte Carlo simulations were performed. The film was modelled rigorously to incorporate the composition and structure of the film. Two field configurations, a 1 x 10 cm2 field and a 10 x 10 cm2 field, were examined. The dose behind the air cavity is reduced by 6 to 7% for both field configurations when a film that intersects the cavity contains the central beam axis. This is due to the attenuation exerted by the film when photons cross the cavity. Offsetting the beam to the cavity and the film by 2 cm removes the dose reduction behind the air cavity completely. Another result was that the rebuild-up behind the cavity for the 10 x 10 cm2 field, albeit less significant than for the 1 x 10 cm2 field, could only be measured by the film that was placed offset with respect to the central beam axis. Although radiochromic film is approximately soft-tissue equivalent and energy independent as compared to radiographic films, care should be taken in the case of inhomogeneous phantoms when the film intersects air cavities and contains the beam central axis. Errors in dose measurement can be expected distal to the air cavity due to attenuation in the film itself. This attenuation would not occur in the absence of the film. Both experiments and Monte Carlo computations support this conclusion.

Air↗

PubMed2003

Monte Carlo model of the Elekta SLiplus accelerator: validation of a new MLC component module in BEAM for a 6 MV beam.

A new component module (CM), called MLCE, has been implemented in the BEAM program. The CM takes into account the particular 'tongue-and-groove' design of the Elekta multi-leaf collimator (MLC) and the air gap between the leaves. The model was validated by two series of measurements and simulations. The first benchmarking series focuses on the interleaf leakage and the intraleaf transmission. The measurement showed a total transmission through the MLC of 1.42% of the open field dose. Two Monte Carlo (MC) simulations were made, the first with the new CM MLCE (inclusive of air gap) and the second with the CM MLCQ (exclusive of air gap), which is available in the BEAM distribution. When the air gap between the leaves was determined by varying the parameters of the leaf geometry within tolerance limits on the technical drawing, the total measured transmission of 1.42% was well reproduced by the CM MLCE. In contrast, MC simulations with MLCQ showed that the transmission through the MLC calculated without the interleaf leakage is only 44% of the total transmitted radiation. The relevance of the detailed MLC modelling was demonstrated also by studying the 'adjacent' tongue-and-groove effect, where two adjacent (not opposing) leaves are complementary, opened or closed. The two complementary leaf settings were simulated both with the CM MLCE and MLCQ. A comparison with measurements was made. In regions covered by two or more leaves, the dose increased by 14% for two leaves and by 40% for more than two leaves when the interleaf leakage was included in the transmission. The tongue-and-groove effect was perfectly reproduced by the MLCE module.

Algorithms↗

PubMed2003

Intra-arterial radionuclide therapy for liver tumours: effect of selectivity of catheterization and 131I-Lipiodol delivery on tumour uptake and response.

Several authors have demonstrated the good tolerance of hepatic intra-arterial 131I-Lipiodol therapy and report survival rates of 21-25% after 1 year in inoperable patients. This study explored the possibility that more selective hepatic arterial instillation could be a strategy for increasing tumoural uptake and response of 131I-Lipiodol. Between June 1999 and September 2001 we selected 24 patients: 14 received a selective instillation of 131I-Lipiodol to the proper hepatic artery (SEL group); and 10 received a hyperselective instillation in the right or left hepatic artery (HYP-SEL group). The individual 131I-Lipiodol activity as a per cent of the injected activity per millilitre of tumour (%IA/ml tumour) was correlated with the selectivity of instillation in 28 tumours and with tumour response in 24 tumours. Differences in tumour response or tumour uptake between the SEL and HYP-SEL groups were not significant. In general, we observed a %IA/ml tumour of 0.05-2.6% for the uptake of 131I-Lipiodol. The uptake was significantly higher in responsive disease than in stable or progressive disease (P=0.002). A large tumour volume was invariably related to low uptake of 131I-Lipiodol and progressive disease (P=0.008). In conclusion, our study does not support the general use of hyper-selective or super-selective intra-arterial administration of 131I-Lipiodol. This result may be extrapolated to similar types of intra-arterial, loco-regional hepatic radionuclide therapy.

Aged↗

PubMed2003

Biodistribution and dosimetry study of 123I-rh-annexin V in mice and humans.

This study reports on the optimization of the labelling procedure of clinical grade 123I-rh-annexin V and on the investigation of the biodistribution and dosimetry of 123I-rh-annexin V, a tracer proposed for the study of apoptosis in mice and humans. Research grade 123I-rh-annexin V was prepared as described previously, whereas clinical grade 123I-rh-annexin V was prepared according to a modified IodoGen method. NMRI mice, 3-4 weeks of age, received research grade 123I-rh-annexin V (74.0+/-3.7 kBq/mouse) by intravenous (i.v.) injection and killed at preset time points. Afterwards, the collected organs, blood, urine and faeces were counted for radioactivity and determined as %ID/g tissue or %ID over time. Secondly, six volunteers with normal liver and kidney function underwent whole-body scans up to 21 h after i.v. injection of clinical grade 123I-rh-annexin V (345+/-38 MBq). Time-activity curves were generated for the organs of interest, e.g., thyroid, heart, liver, kidneys and whole body, by fitting the organ specific geometric mean counts, obtained from region of interest analysis of acquired images in humans. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Clinical grade 123I-rh-annexin V was obtained in radiochemical yields of 87.0+/-6.5% and radiochemical purities >98%. In mice, research grade 123I-rh-annexin V accumulated primarily in liver, kidney, stomach and lung tissue, limiting its usefulness for imaging of ongoing apoptosis in the abdominal and thoracic region. Clearance was predominantly urinary. In humans, acquired images with the clinical grade radioligand showed low lung uptake, resulting in good imaging conditions for the thoracic region. On the other hand, delayed imaging of the abdominal region was impeded due to extensive bowel activity. The highest absorbed doses were received by the thyroid, the kidneys, the heart wall, the liver and bone surfaces. The average effective dose of 123I-rh-annexin V was estimated to be 0.02 mSv.MBq-1. The amount of 123I-rh-annexin V required for in vivo imaging, results in an acceptable effective dose to the patient.

Adult↗

PubMed2002

Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.

The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).

Adult↗

PubMed2002

Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary?

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before (131)I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after (131)I-lipiodol ( n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry ( n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 ( n=17) or 4 ( n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity ( n=31) compared with 0.42%+/-0.20% in the non-KI group ( n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group ( n=19) versus 11.9+/-5.9 Gy in the non-KI group ( n=21). These differences were statistically significant ( P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident ( P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Carcinoma, Hepatocellular↗

PubMed2002

Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low-LET gamma-rays and high-LET fast neutrons.

PURPOSE: To determine by means of the G2 assay the number of chromatid breaks induced by low-LET gamma-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIALS AND METHODS: The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET gamma-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for gamma-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments, the kinetics of chromatid break formation and disappearance were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. RESULTS: No significant differences in the number of chromatid breaks were observed between low-LET gamma-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET gamma-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for gamma-rays and 0.84 h for neutrons were obtained. CONCLUSIONS: Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV x microm(-1) 60Co gamma-rays and 20 keV x microm(-1) fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result of an exchange process which is triggered by a single double-strand break.

Adult↗