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The general population is increasingly exposed to cerium (Ce), which is contained in industrial products or is present as nuclear Ce fission products. Some studies suggested a link between elevated Ce levels and endomyocardial fibrosis. Since breast milk is the optimal, and directly after birth, usually the sole nutrition for newborns, exposure of females to Ce and its transfer to infants by breast-feeding is of concern in neonate protection. Consequently, the transfer rate of Ce from blood to breast milk is of interest for elucidating the Ce exposure of infants. Biomonitoring of paired serum and breast milk samples provides such information about Ce transfer to human milk. Therefore, this study is aimed at clarification of the relationship between Ce in human milk and serum from respective mothers for elucidating Ce enrichment in human milk with possible nutritional risk for newborns. As a prerequisite a strictly quality-controlled Ce determination method applicable to very low Ce concentration was developed, and its figures of merit were determined and found to be sufficient for our purpose. It turned out that Ce concentration in milk from Munich (Germany) and Madrid (Spain) showed a median of 13 ng/L. Ce concentrations in serum were at limit of quantification (LOQ) 10 ng/L (Munich) or 21.6-70.3 ng/L (Madrid), suggesting a higher Ce intake in Madrid. No enrichment from blood to milk was seen, and no elevated nutritional risk for breast-fed babies from Ce was found. Ce in serum, but not in milk, could indicate environmental Ce. [ABSTRACT FROM AUTHOR]

Thermal ionisation mass spectrometry (TIMS) method has been developed for the simultaneous detection of different cerium isotopes in biological samples (i.e., blood and urine) at very low concentrations. The work has been done in the frame of a biokinetic study, where different stable cerium isotopes have been administered orally and intravenously as tracers to the human body. In order to develop an appropriate detection method for the tracers in the biological samples, an optimum sample preparation technique has been set and adapted to the specific requirements of the analysis technique used, i.e., TIMS. For sample evaporation and ionisation, the double tantalum filament technique showed the best results. The ions produced were simultaneously collected on a secondary electron multiplier so that the isotopic ratios of the cerium isotopes in the biological samples could be measured. The technique has been optimised for the determination of cerium down to 1 ng loaded on the evaporation filament corresponding to cerium concentrations of down to 1 ng ml-1 in the blood or urine samples. It has been shown that the technique is reliable in application and enables studies on cerium metabolism and biokinetics in humans without employing radioactive tracers. [ABSTRACT FROM AUTHOR]

An extensive study using stable isotopes of molybdenum as tracers was undertaken to investigate intestinal uptake, systemic kinetics and urinary excretion of molybdenum in healthy human volunteers. In total 63 experiments with 17 volunteers were performed administering the tracers in different chemical forms and measuring their concentrations in blood plasma and urine samples by means of activation analysis and mass spectrometry. Molybdenum was eliminated very rapidly from the circulation. The amount eliminated via the renal pathway was observed to be dependent on several factors, such as form and modality of administration and also the total amount of circulating molybdenum. The fact that the urinary excretion patterns diverged significantly from the current predictions of the International Commission on Radiological Protection model might be relevant when using the model for retrospective intake assessments in case of an accident. On the basis of the experimental data, a more realistic compartmental structure has been presented. [ABSTRACT FROM AUTHOR]

The article focuses on the nationwide survey on natural radionuclides in drinking water that displayed high concentrations of natural uranium in Finland. The concentrations of natural uranium in drinking water of the drilled wells were found out by radiochemical and alpha spectrometric methods in order to assess the radiation dose from the natural uranium to individuals. Uranium contents were assessed in the urinary samples of five members of a Finnish family through the substance of inductively coupled plasma-mass spectrometry. Similarly, theoretical biokinetic modeling of natural uranium integrated for the same persons was executed with the help of follow-up interviews.

The in vitro production of juvenile hormones (JH) was investigated by using corpora allata (CA) of larvae and corpora cardiaca–corpora allata (CC–CA) complexes of adult females of the fall armyworm Spodoptera frugiperda. In female moths, JH release was high compared to that in 5th and 6th instar larvae. Concentrations of 0.11–0.12 mM methionine, 180–200 mM Na+, 5.8–8.3 mM K+, 10–50 mM Ca2+ and a pH range of 5.7–6.3 yielded optimal incorporation of l-[methyl-3H] methionine in vitro by CC–CA complexes. The highest hourly incorporation occurred during a 9-h incubation period following a 1.5-h lag-phase. JH release from CC–CA complexes of adult females was shown to be age-dependent with a peak value on day 2 (approx. 4 pmol h−1 CA−1). By a combination of reversed phase (RP)- and normal phase (NP)-high performance liquid chromatography (HPLC), two major labelled products released by the complex were separated. One compound co-migrated with chemically synthesized JH II diol, the second compound with JH III diol. Only traces of JH II and III could be detected in some samples. Gland extracts also contained both the major radiolabelled products. Double labelling experiments using [3H]methionine and [14C]acetate confirmed their de novo synthesis in CC–CA complexes of female moths. The nature of chemically synthesized reference JH III diol was proved by LC-MS (ESI mass spectrometry) and 1H-NMR (nuclear magnetic resonance spectroscopy). [Copyright &y& Elsevier]

A correction to the article "Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes" that was published in the 2014 issue is presented.

Abstract: The main aim of this study was to determine and evaluate urinary excretion values of uranium in members of the public of Southwest Nigeria living in areas of low environmental uranium. As several uranium mines are running in Nigeria and the operations could be a risk of contamination for the workers as well as for the members of the public, biomonitoring of urine could provide information about the exposure to uranium for the subjects. Therefore, baseline values of uranium in urine are needed from subjects living in areas without mining activities. Volunteers of both genders (age range 3 to 78years) were asked to collect 24h-urine samples. The concentration measurements of uranium in urine were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In addition, urinary creatinine values were determined for normalization of the renal uranium relative to the creatinine concentrations. The urinary uranium concentrations and their creatinine normalized values ranged from <10.4 to 150ngL−1 (median 13.8ngL−1) and from 2.52 to 252.7ngg−1 creatinine (median 33.4ngg−1 creatinine), respectively, for adult subjects above 15years of both genders. An increased uranium excretion value of 61.6ngL−1 (median), and of 76.0ngg−1 creatinine, respectively, were found in young subjects below 15years. The median of daily excreted uranium was estimated to be 14.2ngd−1 for adults and of 45.1ngd−1 for children, respectively. The uranium excretion from males and females living in Nigeria in a non-mining area was comparable to reference values reported from other countries with low level of environmental uranium. The data can be considered as baseline values of urinary uranium in unexposed subjects in Nigeria. [Copyright &y& Elsevier]

Abstract: Biokinetic models describing the uptake, distribution and excretion of trace elements are an essential tool in nutrition, toxicology, or internal dosimetry of radionuclides. Zirconium, especially its radioisotope 95Zr, is relevant to radiation protection due to its production in uranium fission and neutron activation of nuclear fuel cladding material. We present a comprehensive set of human data from a tracer study with stable isotopes of zirconium. The data are used to refine a biokinetic model of zirconium. Six female and seven male healthy adult volunteers participated in the study. It includes 16 complete double tracer investigations with oral ingestion and intravenous injection, and seven supplemental investigations. Tracer concentrations were measured in blood plasma and urine collected up to 100d after tracer administration. The four data sets (two chemical tracer forms in plasma and urine) each encompass 105–240 measured concentration values above detection limits. Total fractional absorption of ingested zirconium was found to be 0.001 for zirconium in citrate-buffered drinking solution and 0.007 for zirconium oxalate solution. Biokinetic models were developed based on the linear first-order kinetic compartmental model approach used by the International Commission on Radiological Protection (ICRP). The main differences of the optimized systemic model of zirconium to the current ICRP model are (1) recycling into the transfer compartment made necessary by the observed tracer clearance from plasma, (2) different parameters related to fractional absorption for each form of the ingested tracer, and (3) a physiologically based excretion pathway to urine. The study considerably expands the knowledge on the biokinetics of zirconium, which was until now dominated by data from animal studies. The proposed systemic model improves the existing ICRP model, yet is based on the same principles and fits well into the ICRP radiation protection approach. [Copyright &y& Elsevier]

Abstract: The aim of this case study was to estimate the bioaccessibility of uranium (238U) and thorium (232Th) from a healing earth by analysing the solubility of these radionuclides in synthetic gastric and intestinal fluids. An easy applicable in vitro test system was used to investigate the fractional mobilization of the soil contaminants being potentially available for absorption under human in vivo conditions. These findings provided the basis for a prospective dose assessment. The solubility experiments were performed using two different in vitro digestion methods. The concentrations of 238U and 232Th in the solutions extracted from the soil were measured by inductively coupled plasma mass spectrometry (ICP-MS). The dissolved fractions in the synthetic gastrointestinal fluid ranged in average from 10.3% to 13.8% for 238U and from 0.3% to 1.6% for 232Th, respectively, depending on the digestion method. Subsequently, the committed effective doses from intake of 238U and 232Th after ingestion of the healing earth during 1 year were evaluated for adult persons. Thereby ingestion dose coefficients calculated as a function of bioaccessibility were used. The dose assessments ranged between 4.3×10−7–1.9×10−6 Sv y−1 for 238U and 5.6×10−7–3.3×10−6 Sv y−1 for 232Th, respectively. On the basis of the assumptions and estimations made, the present work indicates a relatively low radiation risk due to 238U and 232Th after internal exposure of the healing earth. [ABSTRACT FROM AUTHOR]

An increasing number of radiopharmaceuticals and proteins are available for diagnosing and treating various diseases. The demand for existing and newly developed pharmaceutical radionuclides and proteins is steadily increasing. The radiation exposure levels of workers in the radiopharmaceutical industry and nuclear medicine field are closely monitored, specifically their effective dose and equivalent dose, leading to the question, of whether the dawn of radiopharmaceuticals affects the occupational exposure level. This development is analyzed and evaluated with data from the German National Dose Register. Data shows that the effective dose in the work categories production and distribution of radioisotopes as well as nuclear medicine slightly decreased from 1997 to 2021. Over the same period, the hand equivalent dose in nuclear medicine increases steadily, with no discernible trend in production and distribution of radioisotopes. Over the past few decades, intentional efforts and measures have been taken to ensure radiation protection. Instruments for monitoring and dose reduction must be continuously applied. Given the low effective dose, the focus in future shall be on dose reduction following the a s l ow a s r easonably a chievable principle. The development of the hand equivalent dose should be carefully observed in the upcoming years., (Creative Commons Attribution license.)

The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging-(S)-4-(3- 18 F-fluoropropyl)-L-glutamic acid ( 18 F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18 F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in dosimetric calculations. Hence, blood samples should be included in all pharmacokinetic and dosimetric studies for new tracers if possible.

Metabolic challenge protocols, such as the oral glucose tolerance test, can uncover early alterations in metabolism preceding chronic diseases. Nevertheless, most metabolomics data accessible today reflect the fasting state. To analyze the dynamics of the human metabolome in response to environmental stimuli, we submitted 15 young healthy male volunteers to a highly controlled 4 d challenge protocol, including 36 h fasting, oral glucose and lipid tests, liquid test meals, physical exercise, and cold stress. Blood, urine, exhaled air, and breath condensate samples were analyzed on up to 56 time points by MS- and NMR-based methods, yielding 275 metabolic traits with a focus on lipids and amino acids. Here, we show that physiological challenges increased interindividual variation even in phenotypically similar volunteers, revealing metabotypes not observable in baseline metabolite profiles; volunteer-specific metabolite concentrations were consistently reflected in various biofluids; and readouts from a systematic model of β-oxidation (e.g., acetylcarnitine/palmitylcarnitine ratio) showed significant and stronger associations with physiological parameters (e.g., fat mass) than absolute metabolite concentrations, indicating that systematic models may aid in understanding individual challenge responses. Due to the multitude of analytical methods, challenges and sample types, our freely available metabolomics data set provides a unique reference for future metabolomics studies and for verification of systems biology models.

The reliability of biokinetic models is essential for the assessment of internal doses and a radiation risk analysis for the public and occupational workers exposed to radionuclides. In the present study, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. In the first part of the paper, the parameter uncertainty was analyzed for two biokinetic models of zirconium (Zr); one was reported by the International Commission on Radiological Protection (ICRP), and one was developed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU). In the second part of the paper, the parameter uncertainties and distributions of the Zr biokinetic models evaluated in Part I are used as the model inputs for identifying the most influential parameters in the models. Furthermore, the most influential model parameter on the integral of the radioactivity of Zr over 50 y in source organs after ingestion was identified. The results of the systemic HMGU Zr model showed that over the first 10 d, the parameters of transfer rates between blood and other soft tissues have the largest influence on the content of Zr in the blood and the daily urinary excretion; however, after day 1,000, the transfer rate from bone to blood becomes dominant. For the retention in bone, the transfer rate from blood to bone surfaces has the most influence out to the endpoint of the simulation; the transfer rate from blood to the upper larger intestine contributes a lot in the later days; i.e., after day 300. The alimentary tract absorption factor (fA) influences mostly the integral of radioactivity of Zr in most source organs after ingestion.

The reliability of biokinetic models is essential in internal dose assessments and radiation risk analysis for the public, occupational workers, and patients exposed to radionuclides. In this paper, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. The paper is divided into two parts. In the first part of the study published here, the uncertainty sources of the model parameters for zirconium (Zr), developed by the International Commission on Radiological Protection (ICRP), were identified and analyzed. Furthermore, the uncertainty of the biokinetic experimental measurement performed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) for developing a new biokinetic model of Zr was analyzed according to the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. The confidence interval and distribution of model parameters of the ICRP and HMGU Zr biokinetic models were evaluated. As a result of computer biokinetic modelings, the mean, standard uncertainty, and confidence interval of model prediction calculated based on the model parameter uncertainty were presented and compared to the plasma clearance and urinary excretion measured after intravenous administration. It was shown that for the most important compartment, the plasma, the uncertainty evaluated for the HMGU model was much smaller than that for the ICRP model; that phenomenon was observed for other organs and tissues as well. The uncertainty of the integral of the radioactivity of Zr up to 50 y calculated by the HMGU model after ingestion by adult members of the public was shown to be smaller by a factor of two than that of the ICRP model. It was also shown that the distribution type of the model parameter strongly influences the model prediction, and the correlation of the model input parameters affects the model prediction to a certain extent depending on the strength of the correlation. In the case of model prediction, the qualitative comparison of the model predictions with the measured plasma and urinary data showed the HMGU model to be more reliable than the ICRP model; quantitatively, the uncertainty model prediction by the HMGU systemic biokinetic model is smaller than that of the ICRP model. The uncertainty information on the model parameters analyzed in this study was used in the second part of the paper regarding a sensitivity analysis of the Zr biokinetic models.

Systemic kinetics and urinary excretion after intravenous injection of stable strontium 84Sr were evaluated in 42 investigations in human subjects. Tracer concentrations in plasma and urine were determined by thermal ionisation mass spectrometry. The initial strontium plasma clearance measured after tracer administration was found to be much faster than that predicted by the current model of the International Commission of Radiological Protection (ICRP). The biological half-life of the fast component plasma clearance (T(1/2)) was 0.25 h in comparison with 1.1 h of the ICRP value. This early clearance could be the consequence of a more rapid transfer from blood plasma to other compartments of the human body. In vitro blood tests have shown that strontium was not bound to red blood cells. Cumulative urinary excretion is considerably lower than the model prediction. The reason could be the reduced transfer rate of strontium from plasma to urine in the first 12 h after tracer administration. Plasma clearance and urinary excretion showed no dependency on the age or gender of the adult volunteers.

Since the later 1960's, a nationwide survey on natural radionuclides in drinking water showed high concentrations of natural uranium (U) in Finland, especially in uraniferous granite areas. In order to assess the radiation dose from the natural uranium to individuals, the concentrations of natural uranium in drinking water of the drilled wells were determined by radiochemical and alpha spectrometric methods. Uranium contents were measured in the urinary samples of five members of a Finnish family by means of inductively coupled plasma-mass spectrometry. Correspondingly, theoretical biokinetic modeling of natural uranium incorporated for the same persons were performed with the aid of follow-up interviews. The ICRP biokinetic compartmental model and the age-dependent transfer rates for uranium were used to model the intake, transfer, distribution, retention, and excretion of (234)U and (238)U, respectively, from the drinking water for each person of the family. The organ absorbed dose, equivalent dose, and effective dose were evaluated for each family member at time intervals using specific effective energy values calculated by the SEECAL program and compared with recommended values. The modeled urinary excretion rates were found to be mostly higher than the measured values by a factor of three. The mean annual effective dose for this family is 8 muSv y(-1). By comparing the measured and calculated data, estimation of retrospective radiation exposure based on biokinetic modeling and bioassay method is enhanced and, vice versa, the biokinetic and dosimetric models are tested and verified.