Radiopharmacokinetic modelling and radiation dose assessment of 223Ra used for treatment of metastatic castration-resistant prostate cancer.

PURPOSE: Ra-223 dichloride (223Ra, Xofigo®) is used for treatment of patients suffering from castration-resistant metastatic prostate cancer. The objective of this work was to apply the most recent biokinetic model for radium and its progeny to show their radiopharmacokinetic behaviour. Organ absorbed doses after intravenous injection of 223Ra were estimated and compared to clinical data and data of an earlier modelling study. METHODS: The most recent systemic biokinetic model of 223Ra and its progeny, developed by the International Commission on Radiological Protection (ICRP), as well as the ICRP human alimentary tract model were applied for the radiopharmacokinetic modelling of Xofigo® biodistribution in patients after bolus administration. Independent kinetics were assumed for the progeny of 223Ra. The time activity curves for 223Ra were modelled and the time integrated activity coefficients, [Formula: see text] in the source regions for each progeny were determined. For estimating the organ absorbed doses, the Specific Absorbed Fractions (SAF) and dosimetric framework of ICRP were used together with the aforementioned [Formula: see text] values. RESULTS: The distribution of 223Ra after injection showed a rapid plasma clearance and a low urinary excretion. Main elimination was via faeces. Bone retention was found to be about 30% at 4 h post-injection. Similar tendencies were observed in clinical trials of other authors. The highest absorbed dose coefficients were found for bone endosteum, liver and red marrow, followed by kidneys and colon. CONCLUSION: The biokinetic modelling of 223Ra and its progeny may help to predict their distributions in patients after administration of Xofigo®. The organ dose coefficients of this work showed some variation to the values reported from clinical studies and an earlier compartmental modelling study. The dose to the bone endosteum was found to be lower by a factor of ca. 3 than previously estimated.

Measurement, model prediction and uncertainty quantification of plasma clearance of cerium citrate in humans.

Double tracer studies in healthy human volunteers with stable isotopes of cerium citrate were performed with the aim of investigating the gastro-intestinal absorption of cerium (Ce), its plasma clearance and urinary excretion. In the present work, results of the clearance of Ce in blood plasma are shown after simultaneous intravenous and oral administration of a Ce tracer. Inductively coupled plasma mass spectrometry was used to determine the tracer concentrations in plasma. The results show that about 80% of the injected Ce citrate cleared from the plasma within the 5 mins post-administration. The data obtained are compared to a revised biokinetic model of Ce, which was initially developed by the International Commission on Radiological Protection (ICRP). The measured plasma clearance of Ce citrate was mostly consistent with that predicted by the ICRP biokinetic model. Furthermore, in an effort to quantify the uncertainty of the model prediction, the laboratory animal data on which the ICRP biokinetic Ce model is based, was analyzed. The measured plasma clearance and its uncertainty was also compared to the plasma clearance uncertainty predicted by the model. It was found that the measured plasma clearance during the first 15 min after administration is in a good agreement with the modelled plasma clearance. In general, the measured clearance falls inside the 95% confidence interval predicted by the biokinetic model.

The effect of attenuation map, scatter energy window width, and volume of interest on the calibration factor calculation in quantitative 177Lu SPECT imaging: Simulation and phantom study.

PURPOSE: The objective of this study was to evaluate the image degrading factors in quantitative 177Lu SPECT imaging when using both main gamma photopeak energies. METHODS: Phantom measurements with two different vials containing various calibrated activities in air or water were performed to derive a mean calibration factor (CF) for large and small volumes of interest (VOIs). In addition, Monte Carlo simulations were utilized to investigate the effect of scatter energy window width, scatter correction method, such as effective scatter source estimation (ESSE) and triple energy window (TEW), and attenuation map on the quantification of 177Lu. RESULTS: The measured mean CF using large and small VOIs in water was 4.50 ±â€¯0.80 and 4.80 ±â€¯0.72 cps MBq-1, respectively. Simulations showed a reference CF of 3.3 cps MBq-1 for the water-filled phantom considering all photons excluding scattered events. By using the attenuation map generated for 190 keV photons, the calculated CFs for 113 keV and 208 keV are 10% lower than by using the weighted mean energy of 175 keV for 177Lu. The calculated CF using the TEW correction was 17% higher than using the ESSE method for a water-filled phantom. However, our findings showed that an appropriate scatter window combination can reduce this difference between TEW and ESSE methods. CONCLUSIONS: The present work implies that choosing a suitable width of scatter energy windows can reduce uncertainties in radioactivity quantification. It is suggested to generate the attenuation map at 113 keV and 208 keV, separately. Furthermore, using small VOIs is suggested in CF calculation.

A systemic view on the distribution of diet-derived methanol and hepatic acetone in mice.

Volatile organic compounds (VOCs) from breath can successfully be used to diagnose disease-specific pathological alterations in metabolism. However, the exact origin and underlying biochemical pathways that could be mapped to VOC signatures are mainly unknown. There is a knowledge gap regarding the contribution of tissues, organs, the gut microbiome, and exogenous factors to the 'sum signal' from breath samples. Animal models for human disease such as mutant mice provide the possibility to reproduce genetic predisposition to disease, thereby allowing in-depth analysis of metabolic and biochemical functions. We hypothesized that breath VOCs can be traced back to origins and organ-specific metabolic functions by combining breath concentrations with systemic levels detected in different organs and biological media (breath, blood, feces and urine). For this we fed C57Bl/6N mice a grain-based chow or a purified low-fat diet, thereby modifying the emission of methanol in breath whereas acetone levels were unaffected. We then measured headspace concentrations of both VOCs in ex vivo samples of several biological media. Cecum content especially was identified as a likely source of systemic methanol, whereas the liver showed highest acetone concentrations. Our findings are a first step to the systemic mapping of VOC patterns to metabolic functions in mice because differences between VOCs could be traced to different sources in the body. As a future aim, different levels of so-called omics technologies (genomics, proteomics, metabolomics, and breathomics) could be mapped to metabolic pathways in multiple tissues, deepening our understanding of VOC metabolism and possibly leading to early non-invasive biomarkers for human pathologies.

Biokinetic measurements and modelling of urinary excretion of cerium citrate in humans.

Tracer kinetics in healthy human volunteers was studied applying stable isotopes of cerium citrate to obtain biokinetic human data for the urinary excretion of cerium. These data were then used to compare and validate the biokinetic model for lanthanides (cerium) proposed by Taylor and Leggett (Radiat Prot Dosim 105:193-198, 2003), which is substantially improved and more realistic than the biokinetic model currently recommended by the International Commission on Radiological Protection (ICRP Publication 67, 1993); both models are primarily based on animal data. In the present study, 16 adults were investigated and two cerium tracers were simultaneously administered, both intravenously and/or orally. The cerium concentrations in urine were determined by inductively coupled plasma mass spectrometry. Ingested cerium citrate was poorly absorbed, and its low excretion was similar to the prediction of the biokinetic model of Taylor and Leggett. In contrast, after injection of cerium citrate its urinary excretion was rapidly increased, and the model underestimated the experimental results. These results suggest that urinary excretion of cerium may be dependent on the administered chemical form of cerium (speciation).

Estimating the absorption of soil-derived uranium in humans.

The aim of the present study was to improve the estimation of soil-derived uranium absorption in humans. For this purpose, an in vitro solubility assay was combined with a human study by using a specific edible soil low in uranium. The mean bioaccessibility of the soil-derived uranium, determined by the solubility assay in artificial gastrointestinal fluid, was found to be 7.7% with a standard deviation of 0.2%. The corresponding bioavailability of the soil-derived uranium in humans was assumed to be log-normal distributed with a geometric mean of 0.04% and a 95% confidence interval ranging from 0.0049% to 0.34%. Both results were used to calculate a factor, denoted as fA(sol), which describes the relation between the bioaccessibility and the bioavailability of soil-derived uranium. The geometric mean of fA(sol) was determined to be 0.53% with a 95% confidence interval ranging from 0.06% to 4.43%. Based on fA(sol), it is possible to estimate more realistic values on the bioavailability of uranium for highly uranium-contaminated soils in humans by just performing the applied solubility assay. The results of this study can be further used to obtain more reliable results on the internal dose assessment of ingested highly uranium-contaminated soils.

Online breath gas analysis in unrestrained mice by hs-PTR-MS.

The phenotyping of genetic mouse models for human disorders may greatly benefit from breath gas analysis as a noninvasive tool to identify metabolic alterations in mice. Phenotyping screens such as the German Mouse Clinic demand investigations in unrestrained mice. Therefore, we adapted a breath screen in which exhaled volatile organic compounds (VOCs) were online monitored by proton transfer reaction mass spectrometry (hs-PTR-MS). The source strength of VOCs was derived from the dynamics in the accumulation profile of exhaled VOCs of a single mouse in a respirometry chamber. A careful survey of the accumulation revealed alterations in the source strength due to confounders, e.g., urine and feces. Moreover changes in the source strength of humidity were triggered by changes in locomotor behavior as mice showed a typical behavioral pattern from activity to settling down in the course of subsequent accumulation profiles. We demonstrated that metabolic changes caused by a dietary intervention, e.g., after feeding a high-fat diet (HFD) a sample of 14 male mice, still resulted in a statistically significant shift in the source strength of exhaled VOCs. Applying a normalization which was derived from the distribution of the source strength of humidity and accounted for varying locomotor behaviors improved the shift. Hence, breath gas analysis may provide a noninvasive, fast access to monitor the metabolic adaptation of a mouse to alterations in energy balance due to overfeeding or fasting and dietary macronutrient composition as well as a high potential for systemic phenotyping of mouse mutants, intervention studies, and drug testing in mice.

Preparation of Ca-alginate biopolymer beads and investigation of their decorporation characteristics for 85Sr, 238U and 234Th by in vitro experiments.

The aim of this work was to investigate whether Ca-alginate biopolymer beads (CaABBs) can be used to reduce the bioavailability of radionuclides in the gastrointestinal tract of humans. The uptake of strontium, uranium and thorium from a simulated gastrointestinal system was studied by in vitro techniques using CaABBs. This agent was prepared from Na-alginate through cross-linking with divalent calcium ions according to the egg-box model. The effects of process variables such as pH of the gastrointestinal juice, incubation time and solid-to-solution ratio for the removal of radionuclides from the gastrointestinal juice were investigated. The results suggest that CaABBs are a potent material for reducing the bioavailability of radionuclides with a high uptake efficiency in the gastrointestinal tract.

Human breath gas analysis in the screening of gestational diabetes mellitus.

BACKGROUND: We present a pilot study on the feasibility of the application and advantages of online, noninvasive breath gas analysis (BGA) by proton transfer reaction quadrupole mass spectrometry for the screening of gestational diabetes mellitus (GDM) in 52 pregnant women by means of an oral glucose tolerance test (OGTT). SUBJECTS AND METHODS: We collected and identified samples of end-tidal breath gas from patients during OGTT. Time evolution parameters of challenge-responsive volatile organic compounds (VOCs) in human breath gas were estimated. Multivariate analysis of variance and permutation analysis were used to assess feasibility of BGA as a diagnostic tool for GDM. RESULTS: Standard OGTT diagnosis identified pregnant women as having GDM (n = 8), impaired glucose tolerance (n = 12), and normal glucose tolerance (n = 32); a part of this latter group was further subdivided into a "marginal" group (n = 9) because of a marginal high 1-h or 2-h OGTT value. We observed that OGTT diagnosis (four metabolic groups) could be mapped into breath gas data. The time evolution of oxidation products of glucose and lipids, acetone metabolites, and thiols in breath gas after a glucose challenge was correlated with GDM diagnosis (P = 0.035). Furthermore, basal (fasting) values of dimethyl sulfide and values of methanol in breath gas were inversely correlated with phenotype characteristics such as homeostasis model assessment of insulin resistance index (R = -0.538; P = 0.0002, P(corrected) = 0.0034) and pregestational body mass index (R = -0.433; P = 0.0013, P(corrected) = 0.022). CONCLUSIONS: Noninvasive BGA in challenge response studies was successfully applied to GDM diagnosis and offered an insight into metabolic pathways involved. We propose a new approach to the identification of diagnosis thresholds for GDM screening.

Daily urinary excretion of uranium in members of the public of Southwest Nigeria.

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 78 years) 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 150 ng L(-1) (median 13.8 ng L(-1)) and from 2.52 to 252.7 ng g(-1) creatinine (median 33.4 ng g(-1) creatinine), respectively, for adult subjects above 15 years of both genders. An increased uranium excretion value of 61.6 ng L(-1) (median), and of 76.0 ng g(-1) creatinine, respectively, were found in young subjects below 15 years. The median of daily excreted uranium was estimated to be 14.2 ng d(-1) for adults and of 45.1 ng d(-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.

Human biokinetic data and a new compartmental model of zirconium--a tracer study with enriched stable isotopes.

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 (95)Zr, 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 100 d 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.

Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes.

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.

Solubility of uranium and thorium from a healing earth in synthetic gut fluids: a case study for use in dose assessments.

The aim of this case study was to estimate the bioaccessibility of uranium ((238)U) and thorium ((232)Th) 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 (238)U and (232)Th 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 (238)U and from 0.3% to 1.6% for (232)Th, respectively, depending on the digestion method. Subsequently, the committed effective doses from intake of (238)U and (232)Th 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 (238)U and 5.6 × 10(-7)-3.3 × 10(-6) Sv y(-1) for (232)Th, respectively. On the basis of the assumptions and estimations made, the present work indicates a relatively low radiation risk due to (238)U and (232)Th after internal exposure of the healing earth.

Measurement of cerium in human breast milk and blood samples.

The aim of this study was to evaluate the relationship between cerium content in human breast milk and blood plasma or serum. Blood samples and breast milk at various stages of lactation, from 5 days to 51 weeks post partum, were donated by 42 healthy breast-feeding mothers from Munich, Germany and by 26 lactating Spanish mothers from Madrid at 4 weeks post partum. Inductively coupled plasma mass spectrometry was applied for the determination of cerium in the biological samples. Cerium concentration in the digested milk samples from Munich showed low values and the arithmetic mean values ranged between the quantification limit of 5 ng/L up to 65 ng/L. The median value amounted to 13 ng/L. The cerium concentrations in the Spanish breast milk samples amounted to similar low values. The data were about a factor of eight lower than values found in a former study of samples from an eastern German province. All cerium concentrations in the German plasma samples, except for two, were at the quantification limit of 10 ng/L. Interestingly, the serum samples of the Spanish mothers showed cerium values ranging between 21.6 and 70.3 ng/L; these higher data could be explained by an enhanced intake of cerium by humans in Madrid. This could be caused by increased cerium concentrations in particulate matter due to a higher traffic volume in Madrid compared to Munich. The results obtained in this study contribute to setting reference baseline values of cerium in human breast milk and blood plasma/serum and indicate a varying cerium amount depending on the cerium environmental pollution. Possibly, the cerium content in plasma/serum could be an indicator for environmental cerium, which is not valid for breast milk.

Radiation dose assessment of exposure to depleted uranium.

Depleted uranium (DU) is claimed to contribute to human health problems, known as the Gulf War Syndrome and the Balkan Syndrome. Quantitative radiation dose is required to estimate the health risk of DU materials. The influences of the solubility parameters in the human alimentary tract and the respiratory tract systems and the aerosol particles size on the radiation dose of DU materials were evaluated. The dose conversion factor of daily urinary excretion of DU is provided. The retention and excretion of DU in the human body after a contamination at a wound site were predicted. Dose coefficients of DU after ingestion and inhalation were calculated using the solubility parameters of the DU corrosion products in simulated gastric and simulated lung fluid, which were determined in the Helmholtz Zentrum München. (238)U is the main radiation dose contributor per 1 Bq of DU materials. The dose coefficients of DU materials were estimated to be 3.5 x 10(-8) and 2.1 x 10(-6) Sv Bq(-1) after ingestion and inhalation for members of the public. The ingestion dose coefficient of DU materials is about 75% of the natural uranium value. The inhalation dose coefficient of DU material is in between those for Type M and Type S according to the category for inhaled materials defined by the International Commission on Radiological Protection. Radiation dose possibly received from DU materials can directly be estimated by using the dose conversion factor provided in this study, if daily urinary excretion of DU is measured.

Investigations on the solubility of corrosion products on depleted uranium projectiles by simulated body fluids and the consequences on dose assessment.

Ingestion and inhalation of corrosion products covering weathered penetrators made of depleted uranium (DU) represent potential radiological exposure pathways. In order to study the bioavailability of these corrosion products, their solubility was determined using simulated gastric and pulmonary juices. About 75 and 36% of the uranium in the corrosion products were found to be soluble in simulated gastric and pulmonary juices, respectively. The effective dose coefficient for adults after ingestion was calculated to be 0.61 muSv mg(-1) DU. This compares to an effective dose coefficient for an adult of 0.71 muSv mg(-1) for DU materials given by the World Health Organization (WHO). The effective dose coefficient for inhalation was calculated to be 3.7 x 10(-6 )Sv Bq(-1) for workers and 5.3 x 10(-6 )Sv Bq(-1) for members of the public, respectively, which is between those of particles of Types M and S as defined by the International Commission on Radiological Protection (ICRP). The speciation of the corrosion products was investigated by time-of-flight secondary ion mass spectrometry (TOF-SIMS). The mean oxidation state of uranium was found to be 4.6, which suggests that the uranium in the corrosion products consists of a mixture of U(IV) and U(VI) species.

Influence of human biokinetics of strontium on internal ingestion dose of 90Sr and absorbed dose of 89Sr to organs and metastases.

The objective of the present work is to apply the plasma clearance parameters to strontium, previously determined in our laboratory, to improve the biokinetic and dosimetric models of strontium-90 ((90)Sr) used in radiological protection; and also to apply this data for the estimation of the radiation doses from strontium-89 ((89)Sr) after administration to patients for the treatment of the painful bone metastases. Plasma clearance and urinary excretion of stable strontium tracers of strontium-84 ((84)Sr) and strontium-86 ((86)Sr) were measured in GSF-National Research Center for Environment and Health (GSF) in 13 healthy German adult subjects after intravenous injection and oral administration. The biological half-life of strontium in plasma was evaluated from 49 plasma concentration data sets following intravenous injections. This value was used to determine the transfer rates from plasma to other organs and tissues. At the same time, the long-term retention of strontium in soft tissue and whole body was constrained to be consistent with measured values available. A physiological urinary path was integrated into the biokinetic model of strontium. Parameters were estimated using our own measured urinary excretion values. Retention and excretion of strontium were modeled using compartmental transfer rates published by the International Commission on Radiological Protection (ICRP), the SENES Oak Ridge Inc. (SENES), and the Urals Research Center for Radiation Medicine (TBM). The results were compared with values calculated by applying our GSF parameters (GSF). For the dose estimation of (89)Sr, a bone metastases model (GSF-M) was developed by adding a compartment, representing the metastases, into the strontium biokinetic model. The related parameters were evaluated based on measured data available in the literature. A set of biokinetic parameters was optimized to represent not only the early plasma kinetics of strontium but also the long-term retention measured in soft tissue and whole body. The ingestion dose coefficients of (90)Sr were computed and compared with different biokinetic model parameters. The ingestion dose coefficients were calculated as 2.8 x 10(-8), 2.1 x 10(-8), 2.5 x 10(-8) and 3.8 x 10(-8) Sv Bq(-1) for ICRP, SENES, TBM and GSF model parameters, respectively. Moreover, organ absorbed dose for the radiopharmaceutical of (89)Sr in bone metastases therapy was estimated based on the GSF and ICRP biokinetic model parameters. The effective doses were 3.3, 1.8 and 1.2 mSv MBq(-1) by GSF, GSF-M, and ICRP Publication 67 model parameters, respectively, compared to the value of 3.1 mSv MBq(-1) reported by ICRP Publication 80. The absorbed doses of red bone marrow and bone surface, 17 and 21 mGy MBq(-1) calculated by GSF parameters, and 7.1 and 8.8 mGy MBq(-1) by GSF-M parameters, are comparable to the clinical results of 3-19 mGy MBq(-1) for bone marrow and 16 mGy MBq(-1) for bone surface. Based on the GSF-M model, the absorbed dose of (89)Sr to metastases was estimated to be 434 mGy MBq(-1). The strontium clearance half-life of 0.25 h from the plasma obtained in the present study is obviously faster than the value of 1.1 h recommended by ICRP. There are no significant changes for ingestion dose coefficients of (90)Sr using different model parameters. A model including the metastases was particularly developed for dose estimation of (89)Sr treatment for the pain of bone metastases.

Modelling urinary excretion of molybdenum after oral and intravenous administration of stable tracers.

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.

Plasma clearance and urinary excretion after intravenous injection of stable 84Sr in humans.

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.

Human biokinetics of strontium--part II: Final data evaluation of intestinal absorption and urinary excretion of strontium in human subjects after stable tracer administration.

Fractional intestinal absorption (f1 value) and urinary excretion of strontium in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 86Sr and 84Sr using the double-isotope method. Final evaluation of the complete data set confirmed that ingestion of different foodstuff and nutritional factors could influence the fractional gut uptake of strontium. In some cases, significant deviations from the f1 value adopted by the International Commission on Radiological Protection (ICRP) were found. The arithmetic mean (+/- standard deviation) of the f1 values of all experiments performed was determined to be 0.46 (+/- 0.24). The probability distribution function of the f1 values is represented by a lognormal curve with a geometric mean of 0.38 and a geometric standard deviation of 2.06. Urinary excretion in all subjects varied depending on the administered foodstuff in a wide range and differs from the ICRP model, up to 2 days after tracer administration. No age or gender dependence of the absorbed strontium fraction and of the urinary excretion of strontium after an oral load was found.