A puzzling case of contamination with 241Am.

Two people were exposed to and contaminated with 241Am. In vivo determinations of the incorporated 241Am were performed using a whole-body counter and two partial-body counters for the skull and lung, respectively. Additionally, urine samples were analysed to estimate the systemic activity removed from the body. To improve the geometry of the skull measurements, an optimised detector configuration was used, a calibration with three physical phantoms of the human head was conducted, and the morphological variability between the individuals was also considered. The results of the measurements indicate that activity is not deposited in the deep tissues, rather in the skin tissues close to the body surface. Unfortunately, the many open questions relating to the actual circumstances during and after the incident make the interpretation of this case difficult if at all possible.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

Radiation risk and protection of patients in clinical SPECT/CT.

Clinical studies have demonstrated that hybrid single photon emission computed tomography (SPECT)/CT for various diagnostic issues has an added value as compared to SPECT alone. However, the combined acquisition of functional and anatomical images can substantially increase radiation exposure to patients, in particular when using a hybrid system with diagnostic CT capabilities. It is, therefore, essential to carefully balance the diagnostic needs and radiation protection requirements. To this end, the evidence on health effects induced by ionizing radiation is outlined. In addition, the essential concepts for estimating radiation doses and lifetime attributable cancer risks associated with SPECT/CT examinations are presented taking into account both the new recommendations of the International Commission on Radiological Protection (ICRP) as well as the most recent radiation risk models. Representative values of effective dose and lifetime attributable risk are reported for ten frequently used SPECT radiopharmaceuticals and five fully diagnostic partial-body CT examinations. A diagnostic CT scan acquired as part of a combined SPECT/CT examination contributes considerably to, and for some applications even dominates, the total patient exposure. For the common SPECT and CT examinations considered in this study, the lifetime attributable risk of developing a radiation-related cancer is less than 0.27 %/0.37 % for men/women older than 16 years, respectively, and decreases markedly with increasing age at exposure. Since there is no clinical indication for a SPECT/CT examination unless an emission scan has been indicated, the issue on justification comes down to the question of whether it is necessary to additionally acquire a low-dose CT for attenuation correction and anatomical localization of tracer uptake or even a fully diagnostic CT. In any case, SPECT/CT studies have to be optimized, e.g. by adapting dose reduction measures from state-of-the-art CT practice, and exposure levels should not exceed the national diagnostic reference levels for standard situations.

Joint EURADOS-EANM initiative for an advanced computational framework for the assessment of external dose rates from nuclear medicine patients.

BACKGROUND: In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models. RESULTS: Measurements of the ambient dose rate equivalent H*(10) at 1 m from the NM patient have been successfully compared against MC simulations with 5 different codes using the ICRP adult reference computational voxel phantoms, for typical clinical procedures with 99mTc-HDP/MDP, 18FDG and Na131I. All measurement data fall in the 95% confidence intervals, determined for the average simulated results. Moreover, the different MC codes (MCNP-X, PHITS, GATE, GEANT4, TRIPOLI-4®) have been compared for a more realistic scenario where the effective dose rate E of an exposed individual was determined in positions facing and aside the patient model at 30 cm, 50 cm and 100 cm. The variation between codes was lower than 8% for all the radiopharmaceuticals at 1 m, and varied from 5 to 16% for the face-to face and side-by-side configuration at 30 cm and 50 cm. A sensitivity study on the influence of patient model morphology demonstrated that the relative standard deviation of H*(10) at 1 m for the range of included patient models remained under 16% for time points up to 120 min post administration. CONCLUSIONS: The validated computational approach will be further used for the evaluation of effective dose rates per unit administered activity for a variety of close-contact configurations and a range of radiopharmaceuticals as part of risk assessment studies. Together with the choice of appropriate dose constraints this would facilitate the setting of release criteria and patient restrictions.

Dosimetry of 223Ra-chloride: dose to normal organs and tissues.

PURPOSE: (223)Ra-Chloride (also called Alpharadin®) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using (223)Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of (223)Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. METHODS: Absorbed doses were calculated for 25 organs or tissues. RESULTS: Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of (223)Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. CONCLUSION: The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry.

A revised compartmental model for biokinetics and dosimetry of 2-[18F]FDG.

BACKGROUND: The aim was to review available biokinetic data, collect own experimental data, and propose an updated compartmental model for 2-[18F]FDG in the frame of the revision of the ICRP report on dose coefficients for radiopharmaceuticals used in diagnostic nuclear medicine. METHODS: The compartmental model was developed based on published biokinetic data for 2-[18F]FDG. Additional data on urinary excretion in 23 patients (11 males, 12 females) undergoing whole-body PET/CT examinations were obtained within this study. The unknown biokinetic model parameters were derived using the software SAAM II and verified with a modified version of IDAC-Iodide. Dose coefficients for reference adults were calculated with the programme IDAC-Dose 2.1. A dynamic bladder model was employed for urinary bladder dosimetry. RESULTS: The proposed model consists of following compartments: blood, heart wall, brain, liver, lungs, pancreas, spleen, kidneys, urinary bladder content and a generic pool compartment "Other". The latter was introduced to account for 2-[18F]FDG in body organ and tissues besides the explicitly modelled ones. The model predictions showed a good agreement with experimental data. Urinary bladder wall received the highest absorbed dose coefficient of 7.5E-02 mGy/MBq under the assumption of initial urine volume of 100 ml, first voiding at 45 min p.i. and 3.75 h voiding intervals thereafter. The effective dose coefficient calculated according to the current dosimetry framework of ICRP amounted to 1.7E-02 mSv/MBq, compared to 1.9E-02 mSv/MBq in ICRP Publication 128. CONCLUSION: A compartmental model for 2-[18F]FDG was proposed and will be used to replace the descriptive biokinetic model of ICRP Publication 128. The revised model and the provided dose coefficients are expected to improve reference dosimetry for patients administered with 2-[18F]FDG.

Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine - a review.

PURPOSE: The impact on patients' health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET ( www.peddose.net ), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. METHODS: A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed ( www.ncbi.nlm.nih.gov/pubmed ). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. RESULTS: Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. CONCLUSION: It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained.

Risks and safety aspects related to PET/MR examinations.

INTRODUCTION: The introduction of positron emission tomography (PET)/magnetic resonance (MR) systems into medical practice in the foreseeable future may not only lead to a gain in clinical diagnosis compared to PET/computed tomography (CT) imaging due to the superior soft-tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully. OBJECTIVES: This review article summarizes biophysical and biological aspects, which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing radiation in PET and magnetic and electromagnetic fields in MR. On this basis, some considerations concerning the justification and optimization of PET/MR examinations are presented--as far as this is possible at this very early stage. DISCUSSION: Current safety standards do not take into account synergistic effects of ionizing radiation and magnetic and electromagnetic fields. In the light of the developing PET/MR technology, there is an urgent need to investigate this aspect in more detail for exposure levels that will occur at PET/MR systems.

Estimation of patient dose from radiopharmaceuticals using voxel models.

The aim of this study was to demonstrate the advantages of patient dosimetry using voxel models and to present sets of dose estimates for patients of different gender and size. These models offer greater realism with respect to organ shape and topology than the well-established Medical Internal Radiation Dose (MIRD)-type mathematical models. At the National Research Centre for Environment and Health (GSF), specific absorbed fractions have been previously calculated for 4 male and 3 female voxel models, representing different age and stature, for a wide range of source organs. For this study, estimates both for established and new radiopharmaceuticals were performed using biokinetic data from International Commission on Radiological Protection (ICRP). The above calculations allowed for comparison to the MIRD technique in relation to the resulting absorbed organ and effective doses. Furthermore, data sets representing a range of voxel phantoms were investigated. It was found that dose differences among the voxel models can amount up to a factor of 3.

The NUKDOS software for treatment planning in molecular radiotherapy.

The aim of this work was the development of a software tool for treatment planning prior to molecular radiotherapy, which comprises all functionality to objectively determine the activity to administer and the pertaining absorbed doses (including the corresponding error) based on a series of gamma camera images and one SPECT/CT or probe data. NUKDOS was developed in MATLAB. The workflow is based on the MIRD formalism For determination of the tissue or organ pharmacokinetics, gamma camera images as well as probe, urine, serum and blood activity data can be processed. To estimate the time-integrated activity coefficients (TIAC), sums of exponentials are fitted to the time activity data and integrated analytically. To obtain the TIAC on the voxel level, the voxel activity distribution from the quantitative 3D SPECT/CT (or PET/CT) is used for scaling and weighting the TIAC derived from the 2D organ data. The voxel S-values are automatically calculated based on the voxel-size of the image and the therapeutic nuclide ((90)Y, (131)I or (177)Lu). The absorbed dose coefficients are computed by convolution of the voxel TIAC and the voxel S-values. The activity to administer and the pertaining absorbed doses are determined by entering the absorbed dose for the organ at risk. The overall error of the calculated absorbed doses is determined by Gaussian error propagation. NUKDOS was tested for the operation systems Windows(®) 7 (64 Bit) and 8 (64 Bit). The results of each working step were compared to commercially available (SAAMII, OLINDA/EXM) and in-house (UlmDOS) software. The application of the software is demonstrated using examples form peptide receptor radionuclide therapy (PRRT) and from radioiodine therapy of benign thyroid diseases. For the example from PRRT, the calculated activity to administer differed by 4% comparing NUKDOS and the final result using UlmDos, SAAMII and OLINDA/EXM sequentially. The absorbed dose for the spleen and tumour differed by 7% and 8%, respectively. The results from the example from radioiodine therapy of benign thyroid diseases and the example given in the latest corresponding SOP were identical. The implemented, objective methods facilitate accurate and reproducible results. The software is freely available.

[Acquisition and assessment of patient exposure in diagnostic radiology and nuclear medicine]. / Erfassung und Bewertung der Patientenexposition in der diagnostischen Radiologie und Nuklearmedizin.

The regular annual monitoring of patient exposure in radiation diagnostics, as performed by the Federal Office for Radiation Protection (BfS), plays an important role in evaluating the awareness of radiological quality and safety in Germany and the risk-benefit optimization for patients. For the reporting year 1997, X-ray diagnostics resulted in a mean effective dose of 2 +/- 0.5 mSv per head of population. The underlying frequency of medical X-ray examinations was approximately 136 million, i.e., 1.7 examinations annually per head of population. In terms of nuclear medicine diagnostics, the patients exposure amounted to approximately 0.15 mSv effective dose per head of population. In this case, the number of examinations amounted to approximately 4 million, corresponding to a frequency of approximately 0.05 examinations annually per head of population. The paper discusses factors influencing the calculation of exposure, as well as the lack of an internationally accepted protocol to evaluate patient exposure.

Metrics, dose, and dose concept: the need for a proper dose concept in the risk assessment of nanoparticles.

In order to calculate the dose for nanoparticles (NP), (i) relevant information about the dose metrics and (ii) a proper dose concept are crucial. Since the appropriate metrics for NP toxicity are yet to be elaborated, a general dose calculation model for nanomaterials is not available. Here we propose how to develop a dose assessment model for NP in analogy to the radiation protection dose calculation, introducing the so-called "deposited and the equivalent dose". As a dose metric we propose the total deposited NP surface area (SA), which has been shown frequently to determine toxicological responses e.g. of lung tissue. The deposited NP dose is proportional to the total surface area of deposited NP per tissue mass, and takes into account primary and agglomerated NP. By using several weighting factors the equivalent dose additionally takes into account various physico-chemical properties of the NP which are influencing the biological responses. These weighting factors consider the specific surface area, the surface textures, the zeta-potential as a measure for surface charge, the particle morphology such as the shape and the length-to-diameter ratio (aspect ratio), the band gap energy levels of metal and metal oxide NP, and the particle dissolution rate. Furthermore, we discuss how these weighting factors influence the equivalent dose of the deposited NP.

Ninth Annual Warren K. Sinclair Keynote Address: effects of childhood radiation exposure: an issue from computed tomography scans to Fukushima.

The acute and chronic effects of radiation on children have been and will continue to be of great social, public health, scientific, and clinical importance. The focus of interest on ionizing radiation and children has been clear for over half a century and ranges from the effects of fallout from nuclear weapons testing to exposures from accidents, natural radiation, and medical procedures. There is a loosely stated notion that "children are three to five times more sensitive to radiation than adults." Is this really true? In fact, children are at greater risk for some health effects, but not all. For a few sequelae, children may be more resistant than adults. Which are those effects? How and why do they occur? While there are clear instances of increased risk of some radiation-induced tumors in children compared to adults, there are other tumor types in which there appears to be little or no difference in risk by age at exposure and some in which published models that assume the same relative increase in risks for child compared to adult exposures apply to nearly all tumor types are not supported by the scientific data. The United Nations Scientific Committee on Effects of Atomic Radiation (UNSCEAR) has a task group producing a comprehensive report on the subject. The factors to be considered include relevant radiation sources; developmental anatomy and physiology; dosimetry; and stochastic, deterministic, and hereditary effects.

Radiation protection for pregnant workers and their offspring: a recommended approach for monitoring.

Radiation protection of pregnant workers and their offspring is an issue that has been referenced in the literature by the International Commission on Radiological Protection (ICRP), the International Atomic Energy Agency (IAEA) and other international institutions. Several documents of the ICRP address the issue of the protection of the pregnant workers. The new ICRP recommendations refer to the control of working conditions of a pregnant worker, after declaration of pregnancy, such that it is unlikely that the additional dose to the fetus will exceed about 1 mSv during the remainder of pregnancy. The IAEA Basic Safety Standards present similar recommendations. The IAEA is preparing a technical document that provides guidance on these issues.

The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.

Therapy of ankylosing spondylitis with 224Ra-radium chloride: dosimetry and risk considerations.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease which reduces the quality of life and leads to disability in approximately one-third of the patients. The spectrum of therapeutic modalities is limited. The renaissance of the use of (224)Ra-radium chloride for AS treatment, however, gives rise to concern which should result in the reconsideration of (224)Ra dosimetry and in the discussion of the risks associated with this treatment. The present study introduces new dosimetric calculations for alpha and beta/gamma rays performed according to the model proposed by the International Commission on Radiological Protection (ICRP). After a treatment schedule of 10 intravenous injections, each with 1 MBq of (224)Ra, the absorbed doses were calculated to be highest on the bone surface of the patient (4.4 Gy) with a resulting effective dose of 2.5 Sv.

A survey of PET activity in Germany during 1999.

Positron emission tomography (PET) is the most powerful molecular imaging technique currently available for clinical use. The aim of this study was to provide public health information on PET procedures carried out in Germany - a country with a very high number of PET installations. To this end, all facilities that in 1999 were running at least one dedicated PET system were contacted and requested to provide information in a questionnaire on the radiopharmaceuticals applied, the total number and age distribution of patients and volunteers examined, the main diagnostic applications and the range of administered activities. Based on the information provided by 48 of the 60 PET facilities in Germany, an annual frequency of about 0.34 PET procedures per 1,000 inhabitants was estimated, associated with an annual per capita effective dose of about 1.9 micro Sv. Averaged over all PET procedures, the mean effective dose to patients was 5.6 mSv. The age distribution of patients and volunteers was skewed markedly towards higher ages; only a very small fraction (<3%) of patients were children younger than 15 years while older patients, and especially those in the age group between 41 and 65 years, were overrepresented relative to the general population. In total, 28 different PET radiopharmaceuticals were used, with only half of these having been administered to more than 20 patients each. The most frequently applied radiotracer was the glucose analogue 2-[(18)F]fluoro-2-deoxy- D-glucose (FDG), which was utilised in more than 84% of all PET procedures. For this tracer, the median value for activities applied for examinations in the three-dimensional (3D) acquisition mode was only half of that used for two-dimensional (2D) measurements. Based on a statistical analysis of the distribution of mean FDG activities administered to patients in the 48 PET facilities who responded to our inquiry, diagnostic reference levels of 370 and 200 MBq are proposed for the 2D and the 3D mode, respectively.