Dose assessment following an overexposure of a worker at a Swiss nuclear power plant.

AIM: The aim of this work was to assess the doses received by a diver exposed to a radiation source during maintenance work in the fuel transfer pool at a Swiss nuclear power plant, and to define whether the statutory limit was breached or not. METHOD: Onsite measurements were carried out and different scenarios were simulated using the MicroShield Software and the MCNPX Monte Carlo radiation transport code to estimate the activity of the irradiating object as well as the doses to the limbs and the effective dose delivered to the operator. RESULTS: The activity of the object was estimated to 1.8 TBq. From the various dose estimations, a conservative value of 7.5 Sv was proposed for the equivalent dose to the skin on the hands and an effective dose of 28 mSv. CONCLUSION: The use of different experimental and calculation methods allowed us to accurately estimate the activity of the object and the dose delivered to the diver, useful information for making a decision on the most appropriate scheme of follow up for the patient.

Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide.

PURPOSE: The biokinetics and dosimetry of (111)In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and (111)In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. METHODS: Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. RESULTS: Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and ß half-lives, but the ß fraction of NOCATE was double that of OCTREO. Blood T (1/2)ß for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 µSv/MBq) exceeded that of OCTREO (52 µSv/MBq), and the latter result was similar to the ICRP 106 value of 54 µSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. CONCLUSION: NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.

Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. METHODS: Planar and SPECT data were available for a patient examined with (111)In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., (111)In, (90)Y and (177)Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. RESULTS: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for (90)Y and (177)Lu. Nevertheless, for (111)In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT. CONCLUSIONS: The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.

Usefulness of specific calibration coefficients for gamma-emitting sources measured by radionuclide calibrators in nuclear medicine.

PURPOSE: In nuclear medicine, the activity of a radionuclide is measured with a radionuclide calibrator that often has a calibration coefficient independent of the container type and filling. METHODS: To determine the effect of the container on the accuracy of measuring the activity injected into a patient, The authors simulated a commercial radionuclide calibrator and 18 container types most typically used in clinical practice. The instrument sensitivity was computed for various container thicknesses and filling levels. Monoenergetic photons and electrons as well as seven common radionuclides were considered. RESULTS: The quality of the simulation with gamma-emitting sources was validated by an agreement with measurements better than 4% in five selected radionuclides. The results show that the measured activity can vary by more than a factor of 2 depending on the type of container. The filling level and the thickness of the container wall only have a marginal effect for radionuclides of high energy but could induce differences up to 4%. CONCLUSIONS: The authors conclude that radionuclide calibrators should be tailored to the uncertainty required by clinical applications. For most clinical cases, and at least for the low-energy gamma and x-ray emitters, measurements should be performed with calibration coefficients specific to the container type.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

PURPOSE: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity. The authors present here an adaptation of the simple sphere-based model from which cellular level dosimetry for macroscopic tumors and their end point quantities, such as TCP, may be extrapolated more reliably. METHODS: Ten homogenous spheres representing tumors of different sizes were constructed in GEANT4. The radionuclide 131I was randomly allowed to decay for each model size and for seven different ratios of number of decays to number of cells, N(r): 1000, 500, 200, 100, 50, 20, and 10 decays per cell. The deposited energy was collected in radial bins and divided by the bin mass to obtain the average bin absorbed dose. To simulate a cellular model, the number of cells present in each bin was calculated and an absorbed dose attributed to each cell equal to the bin average absorbed dose with a randomly determined adjustment based on a Gaussian probability distribution with a width equal to the statistical uncertainty consistent with the ratio of decays to cells, i.e., equal to Nr-1/2. From dose volume histograms the surviving fraction of cells, equivalent uniform dose (EUD), and TCP for the different scenarios were calculated. Comparably sized spherical models containing individual spherical cells (15 microm diameter) in hexagonal lattices were constructed, and Monte Carlo simulations were executed for all the same previous scenarios. The dosimetric quantities were calculated and compared to the adjusted simple sphere model results. The model was then applied to the Bortezomib-induced enzyme-targeted radiotherapy (BETR) strategy of targeting Epstein-Barr virus (EBV)-expressing cancers. RESULTS: The TCP values were comparable to within 2% between the adjusted simple sphere and full cellular models. Additionally, models were generated for a nonuniform distribution of activity, and results were compared between the adjusted spherical and cellular models with similar comparability. The TCP values from the experimental macroscopic tumor results were consistent with the experimental observations for BETR-treated 1 g EBV-expressing lymphoma tumors in mice. CONCLUSIONS: The adjusted spherical model presented here provides more accurate TCP values than simple spheres, on par with full cellular Monte Carlo simulations while maintaining the simplicity of the simple sphere model. This model provides a basis for complementing and understanding laboratory and clinical results pertaining to radiopharmaceutical therapy.

MODELLING THE EXPOSURE OF RESIDENTS OF A RADIUM-CONTAMINATED LIVING PLACE.

Within the framework of the Swiss Radium Action Plan 2015-22, which aims to investigate and remediate sites contaminated by the radium used in the Swiss watch industry, a reference level of 1 mSv per y has been defined for the exposure of residents. An additional protection objective has been set for soil contamination, which should not exceed the value of 1000 Bq per kg 226Ra. Based on measurements on the study sites, the doses received by residents were calculated accordingly to the methodology, in both indoor and outdoor areas, taking into account external exposure and ingestion. The site diagnosis approach consists of a screening procedure based on a rapid measurement, followed, if necessary, by additional analysis to estimate doses. Sites where modelling indicates that the reference level or the complementary protection objective for soil contamination have been exceeded are subject to remediation. The application of the methodology based on these radiological criteria to 752 sites diagnosed until December 2020 indicates a rate of sites (buildings and outdoor areas) requiring remediation of ~16%. The annual doses to residents calculated by modelling are between 1 and 20 mSv per y for these sites.

Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry.

In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high alpha/beta), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial activity ratio and the S value ratio between the two. In some scenarios, projected BED based on both the cortex and the medulla is a more appropriate constraint on the administered activity than the BED based on the cortex only. Furthermore, different fractionated regimens were considered to reduce renal toxicity. The MIRD-based BED formalism is expected to be useful for patient-specific adjustments of activity and to facilitate the investigation of dose-toxicity correlations with respect to dose-rate and tissue repair mechanism.

Determination of 226Ra at low levels in environmental, urine, and human bone samples and 223Ra in bone biopsy using alpha-spectrometry and metrological traceability to 229Th/225Ra or 226Ra.

226Ra is a natural radioelement emitting α and γ radiations. It can be highly concentrated in TENORM materials from the petroleum or fertilizer industries. In Switzerland, 226Ra is currently a radioactive inheritance problem from the watch industry. Furthermore, 223Ra is a radium isotope used in nuclear medicine to treat bone metastasis. There exist several methods to measure radium using alpha or gamma spectrometry or using 222Rn emanation technique. The limitations of these methods are due to the required detection limits and the nature of the samples. When using alpha spectrometry to reach very low detection limits, critical technical hitches often arise because of the difficulties in separating radium from barium, in removing organics eluted from the separating chromatography column, and in plating radium. Moreover, overall chemical recovery of radium is often not reproducible, depending on the studies. Here we propose a method that separates radium from other alkaline-earth cations using cation exchange chromatography and selective complex formation by EDTA and DCTA. Radium is completely free of the 229Th tracer and its daughter products, particularly 225Ac. Organics from the column are removed in a further purification step so that radium can be plated with acceptable yields in a HCl/HNO3/ethanol solution. We successfully applied the method to soil, water, urine and human bone samples and further extended it to the determination of 223Ra in a bone biopsy, using 226Ra as an internal tracer.

Model of ambient dose equivalent for radium contamination: Dependence on the geometry of the source.

Industrial activities involving radium sources, such as watchmaking, were still common up until the 1960s. They produced contaminations in building materials and the soil in a large variety of geometries. The potential remediation of such places requires instruments that are properly calibrated as well as adequate procedures. We have developed a model that estimates the rate of ambient dose equivalent H˙∗(10) at 10 cm and 1 m from a source of 226Ra and its progeny in both the soil or the building materials. Our model, described here, uses Monte Carlo (GEANT4) computed yield functions of H˙∗(10) per unit activity induced by point-like sources in different contaminated materials. Fit functions of the yield curve of H˙∗(10) are provided for outdoor contamination. The model can be used for any geometrical activity distribution and we present an example showing the dependency of H˙∗(10) on the diameter and the depth profile of the sources, for both outdoor and indoor contamination.

First in-human radiation dosimetry of the gastrin-releasing peptide (GRP) receptor antagonist 68Ga-NODAGA-MJ9.

BACKGROUND: Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of 68Ga-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2 h after tracer injection. To be used as input in OLINDA/EXM 2.0, time-integrated activity coefficients were derived from manually drawn regions of interest over the following body regions: brain, thyroid, lungs, heart, liver, gallbladder, spleen, stomach, kidneys, adrenals, red marrow, pancreas, intestines, urinary bladder and whole body. Organ absorbed doses and effective dose (ED) were calculated with OLINDA/EXM 2.0 using the NURBS voxelized phantoms adjusted to the ICRP-89 organ masses and ICRP103 tissue-weighting factors. Additional absorbed dose estimations were performed with OLINDA/EXM 1.1 to be comparable with similar previous publications. RESULTS: The body regions receiving the highest absorbed doses were the pancreas, the urinary bladder wall, the small intestine and the kidneys (260, 69.8, 38.8 and 34.8 µGy/MBq respectively). The ED considering a 30-min urinary voiding cycle was 17.6 µSv/MBq in male patients. The increment of voiding time interval produced a significant increase of absorbed doses in bladder, prostate and testes, as well as an increase of ED. ED also increased if calculated with OLINDA/EXM 1.1. These results have been discussed in view of similar publications on bombesin analogues or on other commonly used theranostic peptides. CONCLUSIONS: The pancreas is the most irradiated organ after the injection of 68Ga-NODAGA-MJ9, followed by the urinary bladder wall, the small intestine and the kidneys. ED is in the same range of other common 68Ga-labelled peptides. Differences with similarly published studies on bombesin analogues exist, and are mainly dependent on the methodology used for absorbed dose calculations. TRIAL REGISTRATION: Clinicaltrial.Gov identifier: NCT02111954 , posted on 11/042014.

REMEDIATION OF RADIUM LEGACIES FROM THE SWISS WATCH INDUSTRY.

Discovery of radioactive radium contaminations in a former landfill site in Biel was made in 2014. Following this, it was decided to search for and remediate sites that had possibly been contaminated with radium as a result of its use in the watchmaking industry between 1920 and 1960. This work describe the general approach to identify survey and remediate affected sites. The methods is based on the concept of existing exposure situations as developed by the International Commission on Radiological Protection, and is supported by an action plan for radium 2015-2019 approved by the Federal Council in 2015. The plan comprises four steps: the search for potentially contaminated sites, the measurement and assessment of each site, the remediation of those sites where the public would be exposed to an annual dose higher than 1 mSv, and actions to secure the landfill sites. The arrangements for each step are described in the present article. The measurement and remediation procedures imply intrusions into the privacy of the inhabitants. This requires the public authorities to actively inform the population and to develop an effective and transparent means of communication. The actions developed for this are also described.

Modeling of geogenic radon in Switzerland based on ordered logistic regression.

PURPOSE: The estimation of the radon hazard of a future construction site should ideally be based on the geogenic radon potential (GRP), since this estimate is free of anthropogenic influences and building characteristics. The goal of this study was to evaluate terrestrial gamma dose rate (TGD), geology, fault lines and topsoil permeability as predictors for the creation of a GRP map based on logistic regression. METHOD: Soil gas radon measurements (SRC) are more suited for the estimation of GRP than indoor radon measurements (IRC) since the former do not depend on ventilation and heating habits or building characteristics. However, SRC have only been measured at a few locations in Switzerland. In former studies a good correlation between spatial aggregates of IRC and SRC has been observed. That's why we used IRC measurements aggregated on a 10 km × 10 km grid to calibrate an ordered logistic regression model for geogenic radon potential (GRP). As predictors we took into account terrestrial gamma doserate, regrouped geological units, fault line density and the permeability of the soil. RESULTS: The classification success rate of the model results to 56% in case of the inclusion of all 4 predictor variables. Our results suggest that terrestrial gamma doserate and regrouped geological units are more suited to model GRP than fault line density and soil permeability. CONCLUSION: Ordered logistic regression is a promising tool for the modeling of GRP maps due to its simplicity and fast computation time. Future studies should account for additional variables to improve the modeling of high radon hazard in the Jura Mountains of Switzerland.

First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK.

BACKGROUND: Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of 68Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of 68Ga-NODAGA-RGDyK in the five consecutive patients included in a clinical imaging protocol of carotid atherosclerotic plaques. Five male patients underwent whole-body time-of-flight (TOF) PET/CT scans 10, 60 and 120 min after tracer injection (200 MBq). Quantification of 68Ga activity concentration was first validated by a phantom study. To be used as input in OLINDA/EXM, time-activity curves were derived from manually drawn regions of interest over the following organs: brain, thyroid, lungs, heart, liver, spleen, stomach, kidneys, red marrow, pancreas, small intestine, colon, urinary bladder and whole body. A separate dosimetric analysis was performed for the choroid plexuses. Female dosimetry was extrapolated from male data. Effective doses (EDs) were estimated according to both ICRP60 and ICRP103 assuming 30-min and 1-h voiding cycles. RESULTS: The body regions receiving the highest dose were urinary bladder, kidneys and choroid plexuses. For a 30-min voiding cycle, the EDs were 15.7 and 16.5 µSv/MBq according to ICRP60 and ICRP103, respectively. The extrapolation to female dosimetry resulted in organ absorbed doses 17% higher than those of male patients, on average. The 1-h voiding cycle extrapolation resulted in EDs of 19.3 and 19.8 µSv/MBq according to ICRP60 and ICRP103, respectively. A comparison is made with previous mouse dosimetry and with other human studies employing different RGD-based radiopharmaceuticals. CONCLUSIONS: According to ICRP60/ICRP103 recommendations, an injection of 200 MBq 68Ga-NODAGA-RGDyK leads to an ED in man of 3.86/3.92 mSv. For future therapeutic applications, specific attention should be directed to delivered dose to kidneys and potentially also to the choroid plexuses. TRIAL REGISTRATION: Clinical trial.gov, NCT01608516.

Partition Model-Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison.

90Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment 99mTc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of 99mTc-MAA SPECT/CT and posttreatment dosimetry based on 90Y time-of-flight (TOF) PET/CT. METHODS: We compared the 99mTc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with 90Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment 90Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the 99mTc-MAA SPECT/CT and 90Y TOF PET/CT data. Mean absorbed dose ([Formula: see text]) was evaluated to compute the predicted-to-actual dose ratio ([Formula: see text]) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance ([Formula: see text]) was used to measure accuracy ([Formula: see text]) and precision (ρ). RESULTS: Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose [Formula: see text] was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. [Formula: see text] was 1.46 ± 0.58 (0.65-2.53) for glass and 1.16 ± 0.41 (0.54-2.54) for resin, and the respective values for [Formula: see text] were 0.88 ± 0.15 (0.56-1.00) and 0.86 ± 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between [Formula: see text] and [Formula: see text] (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller ([Formula: see text] = 0.93 and [Formula: see text] = 0.95 vs. [Formula: see text] = 0.57 and [Formula: see text] = 0.93; P < 0.05). CONCLUSION: In 90Y radioembolization of HCC, predictive dosimetry based on 99mTc-MAA SPECT/CT provided good estimates of absorbed doses calculated from posttreatment 90Y TOF PET/CT for tumor and nontumor tissues. The low variability of [Formula: see text] demonstrates that pretreatment dosimetry is particularly suitable for minimizing radiation-induced hepatotoxicity.

(210)Po poisoning as possible cause of death: forensic investigations and toxicological analysis of the remains of Yasser Arafat.

The late president of the Palestinian Authority, Yasser Arafat, died in November 2004 in Percy Hospital, one month after having experienced a sudden onset of symptoms that included severe nausea, vomiting, diarrhoea and abdominal pain and which were followed by multiple organ failure. In spite of numerous investigations performed in France, the pathophysiological mechanisms at the origin of the symptoms could not be identified. In 2011, we found abnormal levels of polonium-210 ((210)Po) in some of Arafat's belongings that were worn during his final hospital stay and which were stained with biological fluids. This finding led to the exhumation of Arafat's remains in 2012. Significantly higher (up to 20 times) activities of (210)Po and lead-210 ((210)Pb) were found in the ribs, iliac crest and sternum specimens compared to reference samples from the literature (p-value <1%). In all specimens from the tomb, (210)Po activity was supported by a similar activity of (210)Pb. Biokinetic calculations demonstrated that a (210)Pb impurity, as identified in a commercial source of 3MBq of (210)Po, may be responsible for the activities measured in Arafat's belongings and remains 8 years after his death. The absence of myelosuppression and hair loss in Mr Arafat's case compared to Mr Litvinenko's, the only known case of malicious poisoning with (210)Po, could be explained by differences in the time delivery-scheme of intake. In conclusion, statistical Bayesian analysis combining all the evidence gathered in our forensic expert report moderately supports the proposition that Mr Arafat was poisoned by (210)Po.

Predictive analysis and mapping of indoor radon concentrations in a complex environment using kernel estimation: an application to Switzerland.

PURPOSE: The aim of this study was to develop models based on kernel regression and probability estimation in order to predict and map IRC in Switzerland by taking into account all of the following: architectural factors, spatial relationships between the measurements, as well as geological information. METHODS: We looked at about 240,000 IRC measurements carried out in about 150,000 houses. As predictor variables we included: building type, foundation type, year of construction, detector type, geographical coordinates, altitude, temperature and lithology into the kernel estimation models. We developed predictive maps as well as a map of the local probability to exceed 300 Bq/m(3). Additionally, we developed a map of a confidence index in order to estimate the reliability of the probability map. RESULTS: Our models were able to explain 28% of the variations of IRC data. All variables added information to the model. The model estimation revealed a bandwidth for each variable, making it possible to characterize the influence of each variable on the IRC estimation. Furthermore, we assessed the mapping characteristics of kernel estimation overall as well as by municipality. Overall, our model reproduces spatial IRC patterns which were already obtained earlier. On the municipal level, we could show that our model accounts well for IRC trends within municipal boundaries. Finally, we found that different building characteristics result in different IRC maps. Maps corresponding to detached houses with concrete foundations indicate systematically smaller IRC than maps corresponding to farms with earth foundation. CONCLUSIONS: IRC mapping based on kernel estimation is a powerful tool to predict and analyze IRC on a large-scale as well as on a local level. This approach enables to develop tailor-made maps for different architectural elements and measurement conditions and to account at the same time for geological information and spatial relations between IRC measurements.

Improved predictive mapping of indoor radon concentrations using ensemble regression trees based on automatic clustering of geological units.

PURPOSE: According to estimations around 230 people die as a result of radon exposure in Switzerland. This public health concern makes reliable indoor radon prediction and mapping methods necessary in order to improve risk communication to the public. The aim of this study was to develop an automated method to classify lithological units according to their radon characteristics and to develop mapping and predictive tools in order to improve local radon prediction. METHOD: About 240 000 indoor radon concentration (IRC) measurements in about 150 000 buildings were available for our analysis. The automated classification of lithological units was based on k-medoids clustering via pair-wise Kolmogorov distances between IRC distributions of lithological units. For IRC mapping and prediction we used random forests and Bayesian additive regression trees (BART). RESULTS: The automated classification groups lithological units well in terms of their IRC characteristics. Especially the IRC differences in metamorphic rocks like gneiss are well revealed by this method. The maps produced by random forests soundly represent the regional difference of IRCs in Switzerland and improve the spatial detail compared to existing approaches. We could explain 33% of the variations in IRC data with random forests. Additionally, the influence of a variable evaluated by random forests shows that building characteristics are less important predictors for IRCs than spatial/geological influences. BART could explain 29% of IRC variability and produced maps that indicate the prediction uncertainty. CONCLUSION: Ensemble regression trees are a powerful tool to model and understand the multidimensional influences on IRCs. Automatic clustering of lithological units complements this method by facilitating the interpretation of radon properties of rock types. This study provides an important element for radon risk communication. Future approaches should consider taking into account further variables like soil gas radon measurements as well as more detailed geological information.

Strengths and Weaknesses of a Planar Whole-Body Method of (153)Sm Dosimetry for Patients with Metastatic Osteosarcoma and Comparison with Three-Dimensional Dosimetry.

PURPOSE: Dosimetric accuracy depends directly upon the accuracy of the activity measurements in tumors and organs. The authors present the methods and results of a retrospective tumor dosimetry analysis in 14 patients with a total of 28 tumors treated with high activities of (153)Sm-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) for therapy of metastatic osteosarcoma using planar images and compare the results with three-dimensional dosimetry. MATERIALS AND METHODS: Analysis of phantom data provided a complete set of parameters for dosimetric calculations, including buildup factor, attenuation coefficient, and camera dead-time compensation. The latter was obtained using a previously developed methodology that accounts for the relative motion of the camera and patient during whole-body (WB) imaging. Tumor activity values calculated from the anterior and posterior views of WB planar images of patients treated with (153)Sm-EDTMP for pediatric osteosarcoma were compared with the geometric mean value. The mean activities were integrated over time and tumor-absorbed doses were calculated using the software package OLINDA/EXM. RESULTS: The authors found that it was necessary to employ the dead-time correction algorithm to prevent measured tumor activity half-lives from often exceeding the physical decay half-life of (153)Sm. Measured half-lives so long are unquestionably in error. Tumor-absorbed doses varied between 0.0022 and 0.27 cGy/MBq with an average of 0.065 cGy/MBq; however, a comparison with absorbed dose values derived from a three-dimensional analysis for the same tumors showed no correlation; moreover, the ratio of three-dimensional absorbed dose value to planar absorbed dose value was 2.19. From the anterior and posterior activity comparisons, the order of clinical uncertainty for activity and dose calculations from WB planar images, with the present methodology, is hypothesized to be about 70%. CONCLUSION: The dosimetric results from clinical patient data indicate that absolute planar dosimetry is unreliable and dosimetry using three-dimensional imaging is preferable, particularly for tumors, except perhaps for the most sophisticated planar methods. The relative activity and patient kinetics derived from planar imaging show a greater level of reliability than the dosimetry.

Redefining relative biological effectiveness in the context of the EQDX formalism: implications for alpha-particle emitter therapy.

Alpha-particle radiopharmaceutical therapy (αRPT) is currently enjoying increasing attention as a viable alternative to chemotherapy for targeting of disseminated micrometastatic disease. In theory, αRPT can be personalized through pre-therapeutic imaging and dosimetry. However, in practice, given the particularities of α-particle emissions, a dosimetric methodology that accurately predicts the thresholds for organ toxicity has not been reported. This is in part due to the fact that the biological effects caused by α-particle radiation differ markedly from the effects caused by traditional external beam (photon or electron) radiation or ß-particle emitting radiopharmaceuticals. The concept of relative biological effectiveness (RBE) is used to quantify the ratio of absorbed doses required to achieve a given biological response with alpha particles versus a reference radiation (typically a beta emitter or external beam radiation). However, as conventionally defined, the RBE varies as a function of absorbed dose and therefore a single RBE value is limited in its utility because it cannot be used to predict response over a wide range of absorbed doses. Therefore, efforts are underway to standardize bioeffect modeling for different fractionation schemes and dose rates for both nuclear medicine and external beam radiotherapy. Given the preponderant use of external beams of radiation compared to nuclear medicine in cancer therapy, the more clinically relevant quantity, the 2 Gy equieffective dose, EQD2(α/ß), has recently been proposed by the ICRU. In concert with EQD2(α/ß), we introduce a new, redefined RBE quantity, named RBE2(α/ß), as the ratio of the two linear coefficients that characterize the α particle absorbed dose-response curve and the low-LET megavoltage photon 2 Gy fraction equieffective dose-response curve. The theoretical framework for the proposed new formalism is presented along with its application to experimental data obtained from irradiation of a breast cancer cell line. Radiobiological parameters are obtained using the linear quadratic model to fit cell survival data for MDA-MB-231 human breast cancer cells that were irradiated with either α particles or a single fraction of low-LET (137)Cs γ rays. From these, the linear coefficient for both the biologically effective dose (BED) and the EQD2(α/ß) response lines were derived for fractionated irradiation. The standard RBE calculation, using the traditional single fraction reference radiation, gave RBE values that ranged from 2.4 for a surviving fraction of 0.82-6.0 for a surviving fraction of 0.02, while the dose-independent RBE2(4.6) value was 4.5 for all surviving fraction values. Furthermore, bioeffect modeling with RBE2(α/ß) and EQD2(α/ß) demonstrated the capacity to predict the surviving fraction of cells irradiated with acute and fractionated low-LET radiation, α particles and chronic exponentially decreasing dose rates of low-LET radiation. RBE2(α/ß) is independent of absorbed dose for α-particle emitters and it provides a more logical framework for data reporting and conversion to equieffective dose than the conventional dose-dependent definition of RBE. Moreover, it provides a much needed foundation for the ongoing development of an α-particle dosimetry paradigm and will facilitate the use of tolerance dose data available from external beam radiation therapy, thereby helping to develop αRPT as a single modality as well as for combination therapies.