Actinium-225 as an example for monitoring of internal exposure of occupational intakes of radionuclides in face of new nuclear-medical applications for short-lived alpha emitting particles.

Monitoring of internal exposure to short-lived alpha-emitting radionuclides such as actinium-225 (225Ac), which are becoming increasingly important in nuclear medicine, plays an important role in the radiation protection of occupationally exposed persons. After having tested gamma spectrometry, liquid scintillation counting and alpha spectrometry for monitoring of internal exposure, the focus of the present study was on solid phase extraction of 225Ac from urine in combination with alpha spectrometry. The development of the method was based on recent findings from the literature on this topic. The method was used in a pilot phase to monitor internal exposure of four workers who were directly or indirectly involved in the manufacture and/or use of 225Ac. The monitoring protocol allowed a relatively short 24-hour urine sample analysis with excellent recovery of the internal standard, but it did not allow for a detection limit of less than 1 mBq nor a sufficient yield of 225Ac. Based on these results it is concluded that an in vitro excretion analysis alone is not appropriate for monitoring internal exposure to 225Ac. Instead, different radiation monitoring techniques have to be combined to ensure the radiation protection of employees.

Renal and Intestinal Excretion of 90Y and 166Ho After Transarterial Radioembolization of Liver Tumors.

OBJECTIVE. The aim of this study was to evaluate the amount of free radioactivity in renal and intestinal excretions during the first 48 hours after transarterial radioembolization (TARE) procedures on the liver. SUBJECTS AND METHODS. Urinary, intestinal, and biliary excretions of patients who underwent TARE with three different types of microspheres were collected during a postinterventional period of 48 hours (divided into two 24-hour intervals). Radioactivity measurements were performed. The detected amounts of activity were correlated to clinical and procedural characteristics, times of excretion, and microsphere types. RESULTS. Twenty-four patients were evaluated, 10 treated with 90Y-glass, 10 with 90Y-resin, and four with 166Ho-poly-L-lactic acid (PLLA) microspheres. Activity excretion occurred in all cases. The highest total excretion proportions of the injected activities were 0.011% for 90Y-glass, 0.119% for 90Y-resin, and 0.005% for 166Ho-PLLA microspheres. Intestinal excretion was markedly less than renal excretion (p < 0.001). Excretion after TARE with 90Y-resin was statistically significantly higher than with 90Y-glass or 166Ho-PLLA micro-spheres (p = 0.002). For each microsphere type, the excreted activity was independent of the activity of the injected microspheres. CONCLUSION. Renal and intestinal excretion of radioactivity after TARE is low but not negligible. The radiation risk for individuals interacting with patients can be minimized if contact with urine and bile is avoided, particularly during the first 24 hours after the procedure.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism. This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

Chlorine-36 in fossil rat urine: an archive of cosmogenic nuclide deposition during the past 40,000 years.

Knowledge of the production history of cosmogenic nuclides, which is needed for geological and archaeological dating, has been uncertain. Measurements of chlorine-36/chlorine (36Cl/Cl) ratios in fossil packrat middens from Nevada that are radiocarbon-dated between about 38 thousand years ago (ka) and the present showed that 36Cl/Cl ratios were higher by a factor of about 2 before approximately 11 ka. This raises the possibility that cosmogenic production rates just before the close of the Pleistocene were up to 50% higher than is suggested by carbon-14 calibration data. The discrepancy could be explained by addition of low-carbon-14 carbon dioxide to the atmosphere during that period, which would have depressed atmospheric radiocarbon activity. Alternatively, climatic effects on 36Cl deposition may have enhanced the 36Cl/Cl ratios.

Bioassay and alpha spectrometry in indirect monitoring of Spanish workers exposed to enriched uranium.

Workers at risk of exposure to uranium compounds should be monitored and their internal exposure quantified in terms of committed effective dose E(50) in mSv. In vitro bioassay methods can quantify uranium in urine and faeces at low activity levels. Alpha spectrometry (AS) is the most common method used for monitoring alpha-emitting radionuclides in internal dosimetry services. It provides isotopic information and low minimum detectable activity (MDA) values (≤0.50 mBq per sample). This study reports the results of a five-year monitoring of workers exposed to uranium at a Spanish Juzbado facility, which produces nuclear fuel elements enriched with up to 5 % of 235U. Monitoring included about 100 workers per year, most of whom had worked at the facility for more than 10 years before the individual monitoring programme was established. We analysed nearly 550 samples of more than 200 workers over five years. The obtained results indicate that workers were adequately protected from uranium exposure through inhalation and had an acceptably low chronic intake at the facility.

Studies of a urinary biomarker of dietary inorganic sulphur in subjects on diets containing 1-38 mmol sulphur/day and of the half-life of ingested 34SO4(2-).

OBJECTIVE: Sulphites are widely used food additives that may damage health, hence limits are set on their use. They are excreted in urine as sulphate, along with sulphate derived from sulphur amino acids. Dietary intakes of sulphites are hard to determine, so we have tested the utility of urinary nitrogen:sulphate ratio as a biomarker of inorganic sulphur (IS) intake. Additionally we determined the half-life of ingested (34)SO(4)(2-) from its urinary excretion. SUBJECTS: Twenty healthy adult subjects were recruited by poster advertisement, for a 24-h study where they ate specified foods, which were high in IS, in addition to their normal diet. The half-life of ingested (34)SO(4)(2-) was assessed in five healthy volunteers, given 5.9 mmols of Na(2)(34)SO(4) as a single dose and collecting all urine specimens for 72-96 h. Urine and duplicate diets from three previously conducted studies were analysed for nitrogen and sulphate content, thus expanding the range of IS intakes for evaluation. METHODS: Duplicate diets were analysed for IS content by ion exchange chromatography, while IS intake was predicted from urinary sulphate (g/day S)-(urinary nitrogen (g/day)/18.89). (32)S:(34)S ratios were determined by liquid chromatography mass spectrometry/mass spectrometry. RESULTS: The range of IS intake was 1.3-37.5 mmol S/day. Actual and predicted IS intakes were mmol/day+/-s.e. 9.2+/-0.65 and 7.0+/-0.45, respectively, and were correlated r=0.60 (n=108). The mean half-life of ingested (34)SO(4)(2-) was 8.2 h. CONCLUSIONS: From a 24-h urine collection, IS intake from the habitual diet can be determined for groups of individuals. To predict individual intakes of IS, which may include high sporadic amounts from beer and wine, at least 48 h of urine collection would be required.

[Pharmacokinetic parameter and residua of 63Ni-NiCl2 in rat].

Absorption distribution and excretion of 63Ni-NiCl2, administered orally to rats were studied by using liquid scintillation counting method. It was observed that the concentration-time curves in blood fitted the two compartment model of pharmacokinetics, Ka=6.18 h(-1), T(1/2)alpha =0.79 h, T(1/2)beta=40.68 h, CL =0.42 mL kg(-1) h(-1), Tmax =0.53 h, Cmax=24,987.75 min(-1) mL(-1), and Vd=0.016 L kg(-1). After rats were treated by 63Ni-NiCl2 for 15 days, in 22 tissues tested, the contents of 63Ni-NiCl2 in hair, hypothalamus, hypophysis, pancreas, small and large intestines were higher, and the residua of 63Ni-NiCl2 was not discovered in liver, kidney and heart. Radioactivity eliminated was 83.27% by urine and feces, 54.86% by urine, 28.41% by feces.

Simultaneous Determination of Uranium and Depleted Uranium Isotopic Ratio Using Inductively Coupled Mass Spectrometry.

We have developed and validated a method for the simultaneous quantitative measurement of total uranium (TU) and uranium 235 U/238 U isotopic ratio (UIR) in urine by inductively coupled plasma mass spectrometry (ICP-MS) using a Thermo Scientific iCAP-Q instrument. The performance characteristics of the assay were determined to be in compliance with clinical laboratory standards. The assay was linear in the concentration range of 1.0 to 500.0 ng/liter TU. The method was precise and accurate with limits of detection of 2.5 ng/liter for TU and 9.8 ng/liter for UIR. The accuracy was >93% and the coefficient of variation (% CV) was <5.0% for both TU and UIR. All results were within established guidelines and agreed-upon criteria, and the results fell within the certified range for the reference controls. The method has thus been shown to be effective as a simple, precise, and sensitive analytical technique for testing urine samples. © 2018 by John Wiley & Sons, Inc.

Evaluation of in vivo and in vitro dose detection limits for different radionuclides and measurement techniques.

Personal monitoring programs for workers handling radioactive materials are influenced by numerous factors as the measurements of radioactivity in tissues or/and in excreta can be carried out using different techniques. This paper summaries the basic procedures needed for accurate and fast measurement of different radionuclides like (235)U, (234)U, (238)U, (226)Ra, (210)Po, (131)I, (99m)Tc, (134)Cs, (137)Cs, (57)Co, (58)Co, and (60)Co. Overviews of in vitro and in vivo monitoring methods are provided as well as methods used to calculate detection limits and internal radiation dose. For the radionuclides of interest, in vivo and in vitro detection limits were converted into committed effective doses to evaluate the applicability and limitations of the systems used at the laboratory. The results proved that the systems' sensitivity is suitable for use in routine monitoring of workers subject to risk of internal exposure from such radionuclides. Consequently, monitoring programs suggested by the Syrian internal dosimetry laboratory are suitable to detect committed effective doses even below 1mSv in most cases.

Tissue distribution, elimination, and metabolism of dietary sodium [36Cl]chlorate in beef cattle.

Two steers (approximately 195 kg) were each dosed with 62.5 or 130.6 mg/kg body weight sodium [36Cl]chlorate for three consecutive days. All excreta were collected during the dosing and 8 h withdrawal periods. The apparent radiochlorine absorption was 62-68% of the total dose with the major excretory route being urine. Parent chlorate was 65-100% of the urinary radiochlorine; chloride was the only other radiochlorine species present. Similarly, residues in edible tissues were composed of chloride and chlorate with chloride being the major radiolabeled species present. Chlorate represented 28-57% of the total radioactive residues in skeletal muscle; in liver, kidney, and adipose tissues, chlorate ion represented a smaller percentage of the total residues. Chlorate residues in the low dose steer were 26 ppm in kidney, 14 ppm in skeletal muscle, 2.0 ppm in adipose tissue, and 0.7 ppm in liver. These data indicate that sodium chlorate may be a viable preharvest food safety tool for use by the cattle industry.

Effect of sodium [36Cl]chlorate dose on total radioactive residues and residues of parent chlorate in beef cattle.

The objectives of this study were to determine total radioactive residues and chlorate residues in edible tissues of cattle administered at three levels of sodium [36Cl]chlorate over a 24-h period and slaughtered after a 24-h withdrawal period. Three sets of cattle, each consisting of a heifer and a steer, were intraruminally dosed with a total of 21, 42, or 63 mg of sodium [36Cl]chlorate/kg of body weight. To simulate a 24-h exposure, equal aliquots of the respective doses were administered to each animal at 0, 8, 16, and 24 h. Urine and feces were collected in 12-h increments for the duration of the 48-h study. At 24 h after the last chlorate exposure, cattle were slaughtered and edible tissues were collected. Urine and tissue samples were analyzed for total radioactive residues and for metabolites. Elimination of radioactivity in urine and feces equaled 20, 33, and 48% of the total dose for the low, medium, and high doses, respectively. Chlorate and chloride were the only radioactive chlorine species present in urine; the fraction of chlorate present as a percentage of the total urine radioactivity decreased with time regardless of the dose. Chloride was the major radioactive residue present in edible tissues, comprising over 98% of the tissue radioactivity for all animals. Chlorate concentrations in edible tissues ranged from nondetectable to an average of 0.41 ppm in skeletal muscle of the high-dosed animals. No evidence for the presence of chlorite was observed in any tissue. Results of this study suggest that further development of chlorate as a preharvest food safety tool merits consideration.

Excreta Sampling as an Alternative to In Vivo Measurements at the Hanford Site.

The capabilities of indirect radiobioassay by urine and fecal sample analysis were compared with the direct radiobioassay methods of whole body counting and lung counting for the most common radionuclides and inhalation exposure scenarios encountered by Hanford workers. Radionuclides addressed by in vivo measurement included 137Cs, 60Co, 154Eu, and 241Am as an indicator for plutonium mixtures. The same radionuclides were addressed using gamma energy analysis of urine samples, augmented by radiochemistry and alpha spectrometry methods for plutonium in urine and fecal samples. It was concluded that in vivo whole body counting and lung counting capability should be maintained at the Hanford Site for the foreseeable future, however, urine and fecal sample analysis could provide adequate, though degraded, monitoring capability for workers as a short-term alternative, should in vivo capability be lost due to planned or unplanned circumstances.

The effects of internal radiation exposure on cancer mortality in nuclear workers at Rocketdyne/Atomics International.

We examined the effects of chronic exposure to radionuclides, primarily uranium and mixed-fission products, on cancer mortality in a retrospective cohort study of workers enrolled in the radiation-monitoring program of a nuclear research and development facility. Between 1950 and 1994, 2,297 workers were monitored for internal radiation exposures, and 441 workers died, 134 (30.4%) of them from cancer as the underlying cause. We calculated internal lung-dose estimates based on urinalysis and whole-body and lung counts reported for individual workers. We examined cancer mortality of workers exposed at different cumulative lung-dose levels using complete risk-set analysis for cohort data, adjusting for age, pay type, time since first radiation monitored, and external radiation. In addition, we examined the potential for confounding due to chemical exposures and smoking, explored whether external radiation exposure modifies the effects of internal exposure, and estimated effects after excluding exposures likely to have been unrelated to disease onset. Dose-response relations were observed for death from hemato- and lymphopoietic cancers and from upper aerodigestive tract cancers, adjusting for age, time since first monitored, pay type, and external (gamma) radiation dose. No association was found for other cancers, including cancers of the lung. Despite the small number of exposed deaths from specific cancer types and possible bias due to measurement error and confounding, the positive findings and strong dose-response gradients observed suggest carcinogenic effects of internal radiation to the upper aerodigestive tract and the blood and lymph system in this occupational cohort. However, causal inferences require replication of our results in other populations or confirmation with an extended follow-up of this cohort.

The effect of certain variables on the tumor and tissue distribution of tracers. Part 1; Carrier.

Buffalo rats bearing thigh-implanted strain-7777 Morris hepatomas were used as a model for studying the effect of carrier material on the body distribution, tumor uptake, excretion, and tumor-to-background ratios of 67Ga and 54Mn. An effort was also made to observe the changes in 67Ga and 54Mn concentrations induced by carrier in viable tumor and skeletal muscle, relative to their interstitial fluid space. This value is referred to as the Tissue Distribution Index. Carrier manipulation resulted in striking changes in the distribution of the two ions from the carrier-free state. The data also indicated a difference in the pharmacodynamics of 67Ga and 54Mn in malignant and healthy tissues which could be of importance to nuclear medicine and oncology.

Blood and urinary 18F pharmacokinetics following parenteral administration in the rat.

Blood and urinary excretion time courses of 18F administered parenterally to rats were monitored for two hours. The intraperitoneal, subcutaneous, and intravenous routes gave kinetically indistinguishable results after ten minutes following the dose. The blood time course during the first hour following intramuscular dosing showed a relative constancy and suggested a delayed absorption time.

Analysis of urine samples from metastatic bone cancer patients administered 153Sm-EDTMP.

153Sm-EDTMP is currently undergoing clinical evaluation as a radiotherapeutic agent for the relief of pain associated with cancer metastatic to bone. These clinical studies have demonstrated biodistributions similar to those seen earlier in animals, namely, rapid clearance from blood, selective uptake in bone and in particular metastatic bone lesions. The radioactivity not deposited in bone is cleared through the kidneys into the urine. In this study, urine samples collected from 9 patients injected with 153Sm-EDTMP underwent complexation analysis via Pharmacia SP-Sephadex C25 cation exchange chromatography. The results showed 96.9 +/- 1.7% of the radioactivity in the urine to be present as a complex of 153Sm. An HPLC method was developed and it was demonstrated that different complexes of 153Sm could be separated. A non-radioactive analytical standard of the Sm-EDTMP chelate was synthesized, characterized and shown to have the same HPLC retention profile as the 153Sm-EDTMP drug product. HPLC analysis was performed on six urine samples and in each case a single radioactivity peak with an elution profile the same as that of a 153Sm-EDTMP standard was observed. These results indicate that the 153Sm-EDTMP chelate is excreted intact in the urine of patients.

Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats.

Rat plasma distribution data obtained following IV administration of 99mTc(DTPA) alone or after co-administration of 99mTc(DTPA) and 153Gd-labeled Gd(DTPA)2- at 0.001, 0.1, and 1.0 mmol Gd/kg were evaluated using compartmental modeling techniques. A three-compartment open model was found to fit the data significantly better (P less than 0.01) than a two- or four-compartment open model. This model incorporates and links the plasma and urine data and includes a delay to account for the transit time through the kidneys/ureters. The two nonplasma compartments of the model were assumed to be related to rapidly and slowly equilibrating tissues. Tc(DTPA) and Gd(DTPA)2- had nearly identical pharmacokinetic profiles in plasma and the rate constants were essentially the same. No significant dose dependent pharmacokinetic differences were found for the range of Gd(DTPA)2- doses tested. Simulations of the proposed three-compartment model were used to generate concentration-time curves for each of the three compartments.

Occupational exposure to radionuclides in French nuclear power plants: five years excretion monitoring results.

In the French Nuclear Power Plants, monitoring of individual internal exposures is accomplished by lung counting by the medical service of the plant, and on request of the physician by analysis of biological samples in the Saint-Denis Laboratory. A description of the various methods used in the Laboratory for measuring low level activity samples is given. In particular, the performance of routine contamination monitoring by gamma spectrometry of urines with a semiconductor detector is discussed. An automatic system, designed for Marinelli beaker analysis, made up of a sample changer, a germanium detector and a computerized multichannel analyser is presented. The same device is used for counting faecal ashes and nose blows sampled after an incident. The estimation of the incorporated activities is achieved by using a computer program originating from the compartmental metabolic model of the ICRP. This paper presents a survey of routine monitoring of excretions over a period of 5 years, and a discussion of the ICRP Cobalt metabolic models based on the study of its elimination kinetics after occupational intake.

The impact of natural radioactivity from a coal-fired power plant.

In a coal-fired power station burning coal which contained between 14--100 ppm U, 210Pb was detected in the urine of an exposed group of individuals. Chromosome aberrations (complex, numerical and the percentage of total aberrations) were also registered.

Current status of bioassay procedures to detect and quantify previous exposures to radioactive materials. Bioassay Procedures Working Group.

This report was prepared by a working group established by the Oak Ridge Associated Universities (ORAU) for the purpose of assessing the current capabilities of bioassay methods that can be used to determine the occurrence and magnitude of a previous internal deposition of one or more radionuclides. The first five sections discuss general features of the use of in-vitro bioassay samples to achieve this purpose. The remainder of the report is focused on the possible use of urine bioassay procedures to detect and quantify internal depositions of radionuclides that may have occurred in United States occupation troops in Hiroshima or Nagasaki, Japan, prior to 1 July 1946, or to personnel who participated in atmospheric nuclear weapons tests conducted between 1945 and 1962. Theoretical calculations were made to estimate the quantities of various radionuclides produced in a 20-kiloton (kt) nuclear detonation that might still be present in measurable quantities in people today if they were exposed 25 to 40 y ago. Two radionuclides that emerged as good choices for this type of bioassay analysis were 90Sr, which emits beta particles, and 239,240Pu, which emits alpha particles. The current status and future prospects of chemical procedures for analyzing in-vitro urine bioassay samples for these two radionuclides were examined to determine the minimum amounts that could be detected with current methods and how much one might expect the sensitivity of detection to improve in the near future. Most routine 239,240Pu bioassay analyses involve detection by alpha spectrometry. The current minimum detectable amount (MDA) is about 0.74 mBq L-1 (20 fCi L-1), but this could be lowered to 74 muBq L-1 (2 fCi L-1). An MDA of 0.74 mBq L-1 (20 fCi L-1) is adequate for routine bioassay analyses but is too high to detect most uptakes of 239,240Pu that may have occurred 25 to 40 y ago. Methods under development that are or can be much more sensitive and have lower MDAs than alpha spectrometry for 239Pu are fission track analysis and mass spectrometry. Currently, the fission track analysis method has an MDA of about 19 muBq L-1), and this may eventually be lowered to 1.9 muBq L-1 (0.005 fCi L-1). The current MDA for 239Pu by mass spectrometry is about 7.4 mBq L-1 (200 fCi L-1), but the potential exists that it could be lowered to a value of about 0.37 muBq L-1 (0.01 fCi L-1).(ABSTRACT TRUNCATED AT 400 WORDS)