Developing the 134Ce and 134La pair as companion positron emission tomography diagnostic isotopes for 225Ac and 227Th radiotherapeutics.

Developing targeted α-therapies has the potential to transform how diseases are treated. In these interventions, targeting vectors are labelled with α-emitting radioisotopes that deliver destructive radiation discretely to diseased cells while simultaneously sparing the surrounding healthy tissue. Widespread implementation requires advances in non-invasive imaging technologies that rapidly assay therapeutics. Towards this end, positron emission tomography (PET) imaging has emerged as one of the most informative diagnostic techniques. Unfortunately, many promising α-emitting isotopes such as 225Ac and 227Th are incompatible with PET imaging. Here we overcame this obstacle by developing large-scale (Ci-scale) production and purification methods for 134Ce. Subsequent radiolabelling and in vivo PET imaging experiments in a small animal model demonstrated that 134Ce (and its 134La daughter) could be used as a PET imaging candidate for 225AcIII (with reduced 134CeIII) or 227ThIV (with oxidized 134CeIV). Evaluating these data alongside X-ray absorption spectroscopy results demonstrated how success relied on rigorously controlling the CeIII/CeIV redox couple.

Uncertainty analysis in internal dose calculations for cerium considering the uncertainties of biokinetic parameters and S values.

Radioactive cerium and other lanthanides can be transported through the aquatic system into foodstuffs and then be incorporated by humans. Information on the uncertainty of reported dose coefficients for exposed members of the public is then needed for risk analysis. In this study, uncertainties of dose coefficients due to the ingestion of the radionuclides 141Ce and 144Ce were estimated. According to the schema of internal dose calculation, a general statistical method based on the propagation of uncertainty was developed. The method takes into account the uncertainties contributed by the biokinetic models and by the so-called S values. These S-values were derived by using Monte Carlo radiation transport simulations with five adult non-reference voxel computational phantoms that have been developed at Helmholtz Zentrum München, Germany. Random and Latin hypercube sampling techniques were applied to sample parameters of biokinetic models and S values. The uncertainty factors, expressed as the square root of the 97.5th and 2.5th percentile ratios, for organ equivalent dose coefficients of 141Ce were found to be in the range of 1.2-5.1 and for 144Ce in the range of 1.2-7.4. The uncertainty factor of the detriment-weighted dose coefficient for 141Ce is 2.5 and for 144Ce 3.9. It is concluded that a general statistical method for calculating the uncertainty of dose coefficients was developed and applied to the lanthanide cerium. The dose uncertainties obtained provide improved dose coefficients for radiation risk analysis of humans. Furthermore, these uncertainties can be used to identify those parameters most important in internal dose calculations by applying sensitivity analyses.

Fungal spore involvement in the resuspension of radiocaesium in summer.

We observed the atmospheric resuspension of radiocaesium, derived from the Fukushima Dai-ichi Nuclear Power Plant accident, at Namie, a heavily contaminated area of Fukushima, since 2012. During the survey periods from 2012 to 2015, the activity concentrations of radiocaesium in air ranged from approximately 10-5 to 10-2 Bq per m3 and were higher in the warm season than in the cold season. Electron microscopy showed that the particles collected on filters in summer were predominantly of biological origin (bioaerosols), with which the observed radiocaesium activity concentration varied. We conducted an additional aerosol analysis based on fluorescent optical microscopic observation and high-throughput DNA sequencing technique to identify bioaerosols at Namie in 2015 summer. The concentrations of bioaerosols fluctuated the order of 106 particles per m3, and the phyla Basidiomycota and Ascomycota (true Fungi) accounted for approximately two-thirds of the bioaerosols. Moreover, the fungal spore concentration in air was positively correlated with the radiocaesium concentration at Namie in summer 2016. The bioaerosol emissions from Japanese mixed forests in the temperate zone predominately included fungal cells, which are known to accumulate radiocaesium, and should be considered an important scientific issue that must be addressed.

Ce-141-labeled DOTMP: A theranostic option in management of pain due to skeletal metastases.

Owing to its favorable radioactive decay characteristics (T1/2  = 32.51 d, Eß [max] = 434.6 keV [70.5%] and 580.0 keV [29.5%], Eγ  = 145.4 keV [48.5%]), 141 Ce could be envisaged as a theranostic radionuclide for use in nuclear medicine. The present article reports synthesis and evaluation of 141 Ce complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid (DOTMP) as a potent theranostic agent targeting metastatic skeletal lesions. Ce-141 was produced with 314 ± 29 MBq/mg (n = 6) specific activity and >99.9% radionuclidic purity (n = 6). Around 185 MBq dose of [141 Ce]Ce-DOTMP was synthesized with 98.6 ± 0.5% (n = 4) radiochemical yield under optimized conditions of reaction, and the preparation showed adequately high in vitro stability. Biodistribution studies in normal Wistar rats demonstrated significant skeletal localization and retention of injected activity (2.73 ± 0.28% and 2.63 ± 0.22% of injected activity per gram in femur at 3 hours and 14 days post-injection, respectively) with rapid clearance from non-target organs. The results of biodistribution studies were corroborated by serial scintigraphic imaging studies. These results demonstrate the potential utility of 141 Ce-DOTMP as a theranostic molecule for personalized patient care of cancer patients suffering from painful metastatic skeletal lesions.

Simulation study of light transport in laser-processed LYSO:Ce detectors with single-side readout.

A tightly focused pulsed laser beam can locally modify the crystal structure inside the bulk of a scintillator. The result is incorporation of so-called optical barriers with a refractive index different from that of the crystal bulk, that can be used to redirect the scintillation light and control the light spread in the detector. We here systematically study the scintillation light transport in detectors fabricated using the laser induced optical barrier technique, and objectively compare their potential performance characteristics with those of the two mainstream detector types: monolithic and mechanically pixelated arrays. Among countless optical barrier patterns, we explore barriers arranged in a pixel-like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce crystal. We analyze the performance of the detectors coupled to MPPC arrays, in terms of light response functions, flood maps, line profiles, and light collection efficiency. Our results show that laser-processed detectors with both barrier patterns constitute a new detector category with a behavior between that of the two standard detector types. Results show that when the barrier-crystal interface is smooth, no DOI information can be obtained regardless of barrier refractive index (RI). However, with a rough barrier-crystal interface we can extract multiple levels of DOI. Lower barrier RI results in larger light confinement, leading to better transverse resolution. Furthermore we see that the laser-processed crystals have the potential to increase the light collection efficiency, which could lead to improved energy resolution and potentially better timing resolution due to higher signals. For a laser-processed detector with smooth barrier-crystal interfaces the light collection efficiency is simulated to >42%, and for rough interfaces >73%. The corresponding numbers for a monolithic crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a mechanically pixelated array 35% with polished pixel surfaces and 59% with rough surfaces.

Development of a phantom and assessment of (141)Ce as a surrogate radionuclide for flood field uniformity testing of gamma cameras.

This paper describes an indigenous method for development and deployment of rechargeable liquid filled phantom with newly proposed radionuclide (141)Ce for determination of extrinsic uniformity of gamma cameras. Details about design of phantom, neutron irradiation of cerium targets, chemical processing of (141)Ce, charging of phantom with (141)Ce solution and their performance evaluation are presented. Suitability of (141)Ce in quality assurance of gamma cameras used in in-vivo diagnostic imaging procedures has been amply demonstrated.

Distribution and bioavailability of ceria nanoparticles in an aquatic ecosystem model.

Along with the increasing utilization of engineered nanoparticles, there is a growing concern for the potential environmental and health effects of exposure to these newly designed materials. Understanding the behavior of nanoparticles in the environment is a basic need. The present study aims to investigate the distribution and fate of ceria nanoparticles in an aquatic system model which consists of sediments, water, hornworts, fish and snails, using a radiotracer technique. Concentrations of ceria in the samples at regular time intervals were measured. Ceria nanoparticles were readily removed from the water column and partitioned between different organisms. Both snail and fish have fast absorption and clearance abilities. Hornwort has the highest bioaccumulation factors. At the end of the experiment, sediments accumulated most of the nanoparticles with a recovery of 75.7 ± 27.3% of total ceria nanoparticles, suggesting that sediments are major sinks of ceria nanoparticles.

Cyclotron production of radioactive CeO(2) nanoparticles and their application for in vitro uptake studies.

Nowadays, a wide variety of nanoparticles (NPs) are applied in different fields such as medical science and industry. Due to their large commercial volume, the OECD Working Party on Manufactured Nanomaterials (NMs) has proposed to study a set of 14 nanomaterials, one of which being cerium oxide (CeO(2)). In particular, CeO(2) based NPs are widely used in automotive industry, healthcare, and cosmetics. In this paper, we propose a method for the production of radioactive CeO(2) NPs.We demonstrate that they maintain the same physicochemical characteristics as the "cold" ones in terms of size distribution and Zeta potential; we develop a new protocol to assess their cellular interaction in immortalized mouse fibroblast cell line Balb/3T3, a model for the study of basal cytotoxicity and carcinogenic potential induced by chemicals and in the present case by NPs. Experimental result of this work, which shows a quasi-linear concentration-uptake response of cells, can be useful as a reference dose-uptake curve for explaining effects following biological uptake after exposure to CeO(2) NPs.

Removal of cerium ions from aqueous solution by hydrous ferric oxide--a radiotracer study.

Radiotracer technique has been used to study the removal behavior of Ce (III) ions from aqueous solutions by synthesized and well characterized hydrous ferric oxide (HFO). Adsorptive concentration (10(-4)-10(-8) mol dm(-3)), pH (ca 4.0-10.0) and temperature (303-333 K) were examined for assessing optimal conditions for removal of these ions. The uptake of Ce (III) ions, which fitted well for Freundlich and D-R isotherms, increased with increase in the temperature and no significant desorption took place in the studied temperature range. The presence of some anions/cations affected the uptake of metal ion markedly. Irradiation of hydrous ferric oxide and tungsten oxide by using a 11.1×10(9) Bq (Ra-Be) neutron source having a neutron flux of 3.9×10(6) cm(-2) s(-1) with associated γ-dose rate of 1.72 Gy/h did not influence the extent of adsorption of Ce (III) significantly.

Gamma spectrum unfolding for a NaI monitor of radioactivity in aquatic systems: experimental evaluations of the minimal detectable activity.

This paper deals with the experimental evaluation of the minimal detectable activity achievable by unfolding the gamma spectra of a NaI monitor. An aquatic monitor initially developed by the Institut des Radio-Eléments (IRE) is used for the application. Unfolding of the spectra is performed with GRAVEL, a UMG package code, on the basis of a response matrix obtained with MCNP5.1.40. Experimental data have been measured at IRE, in a 20m(3) seawater tank, for known activities of (137)Cs mixed with other gamma emitters ((40)K, (133)Ba, (113)Sn and (139)Ce). Deconvolution allows one to reduce the MDA of (137)Cs by an order of magnitude.

Impact on 141Ce, 144Ce, 95Zr, and 90Sr beta emitter dose coefficients of photon and electron SAFs calculated with ICRP/ICRU reference adult voxel computational phantoms.

The current dose coefficients for internal dose assessment of occupationally exposed persons and the general public were derived using the methodology of the International Commission on Radiological Protection (ICRP), which is similar to the Medical Internal Radiation Dose (MIRD)-type methodology. One component of this methodology is the mathematical representation of the human body (so-called MIRD-type phantoms) developed at the Oak Ridge National Laboratory for calculations of photon specific absorbed fractions (SAFs). Concerning the beta emissions, it is assumed in general that they irradiate only the organ where the radionuclide resides, whereas for walled organs, a fixed fraction of the emitted energy is absorbed within the wall. For the active marrow and bone surface targets, absorbed fractions were explicitly provided in ICRP Publication 30. The ICRP Publications 66 and 100 contain further detailed energy-dependent absorbed fraction data for the airways and the segments of the alimentary tract. In the present work, the voxel phantoms representing the reference male and female adults, recently developed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) in collaboration with the Task Group DOCAL of ICRP Committee 2, were used for the Monte Carlo computation of photon as well as electron SAFs. These voxel phantoms, being constructed from computed tomography (CT) scans of individuals, are more realistic in shape and location of organs in the body than the mathematical phantoms; therefore, they provide photon SAFs that are more precise than those stemming from mathematical phantoms. In addition, electron SAFs for solid and walled organs as well as tissues in the alimentary tract, the respiratory tract, and the skeleton were calculated with Monte Carlo methods using these phantoms to complement the data of ICRP Publications 66 and 100 that are confined to self-irradiation. The SAFs derived for photons and electrons are then used to calculate the dose coefficients of the beta emitters 141Ce, 144Ce, 95Zr, and 90Sr. It is found that the differences of the dose coefficients due to the revised SAFs are much larger for injection and ingestion than for inhalation. The equivalent doses for colon and ingestion with the new voxel-based SAFs are significantly smaller than the values with the MIRD-type photon SAFs and simplifying assumptions for electrons. For lungs and inhalation, no significant difference was observed for the equivalent doses, whereas for injection and ingestion, an increase of the new values is observed.

Comparative stochastic effects of alpha, beta or x-irradiation of the lung of rats.

The stochastic effects in the lung of inhaled, insoluble particles of alpha- and beta-emitting particles and low-linear energy transfer (LET) thoracic irradiation were compared in rats using data from previously conducted studies. Male and female F344 rats were exposed briefly by nasal inhalation to relatively insoluble aerosols of CeO(2) or PuO(2) to achieve a range of four lung burdens. The mean lifetime beta doses to the lung were 3.6 + or - 1.3 Gy, 6.8 + or - 1.7 Gy, 12 + or - 4.5 Gy, and 37 + or - 5.9 Gy. The mean lifetime alpha doses to the lung were 0.06 + or - 0.03 Gy, 0.95 + or - 0.46 Gy, 3.7 + or - 1.6 Gy, and 12 + or - 2.4 Gy. Additional rats were exposed to fractionated thoracic doses of x rays given on 10 successive working days. The lifetime doses to the lung were 3.3 Gy, 5.7 Gy, 11 Gy, and 38 Gy. Appropriate sham controls were included in each group and all groups were observed for their life spans. Lung neoplasms were found after all exposures, with the incidence increasing with radiation dose. Rats exposed to PuO(2) had the highest incidence, 94% in the group with a dose of 12 Gy. The incidence in the groups exposed to inhaled CeO(2) or fractionated thoracic x-irradiation was not significantly different. The incidence of lung tumors in the PuO(2) groups was 21 times higher than that of the groups exposed to the lower LET radiations. These results support a radiation-weighting factor of 20, as recommended by ICRP 60.

Role of magnetite and humic acid in radionuclide migration in the environment.

Sorption of (137)Cs, (90)Sr, (154)Eu and (141)Ce by magnetite has been studied at varying pH (4 to 11) in the presence and absence of humic acid. The sorption studies have also been carried out at varying ionic strength (0.01 to 0.2 M NaClO(4)) and humic acid concentration (2 to 20 mg/L). Percentage sorption of (137)Cs and (90)Sr was found to be pH dependent, with the sorption increasing with increasing pH of the suspension. At any pH, the percentage sorption of (90)Sr was higher than that of (137)Cs. The results have been explained in terms of the electrostatic interaction between the positively charged metal ions and the surface charge of the magnetite which becomes increasingly negative with increasing pH. On the other hand, (154)Eu and (141)Ce were found to be strongly sorbed by the magnetite at all pH values, with the sorption being independent of pH. The strong sorption of trivalent and tetravalent metal ions suggests the role of complexation reactions during sorption, apart from the electrostatic interactions. However, in the case of (141)Ce surface precipitation of Ce(III) formed by reduction of Ce(IV) in the presence of magnetite cannot be ruled out. Presence of humic acid (2 mg/L) was found to have negligible effect on sorption of all metal ions.

Distribution and Translocation of 141Ce (III) in Horseradish.

BACKGROUND AND AIMS: Rare earth elements (REEs) are used in agriculture and a large amount of them contaminate the environment and enter foods. The distribution and translocation of (141)Ce (III) in horseradish was investigated in order to help understand the biochemical behaviour and toxic mechanism of REEs in plants. METHODS: The distribution and translocation of (141)Ce (III) in horseradish were investigated using autoradiography, liquid scintillation counting (LSC) and electron microscopic autoradiography (EMARG) techniques. The contents of (141)Ce (III) and nutrient elements were analysed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). RESULTS: The results from autoradiography and LSC indicated that (141)Ce (III) could be absorbed by horseradish and transferred from the leaf to the leaf-stalk and then to the root. The content of (141)Ce (III) in different parts of horseradish was as follows: root > leaf-stalk > leaf. The uptake rates of (141)Ce (III) in horseradish changed with the different organs and time. The content of (141)Ce (III) in developing leaves was greater than that in mature leaves. The results from EMARG indicated that (141)Ce (III) could penetrate through the cell membrane and enter the mesophyll cells, being present in both extra- and intra-cellular deposits. The contents of macronutrients in horseradish were decreased by (141)Ce (III) treatment. CONCLUSIONS: (141)Ce (III) can be absorbed and transferred between organs of horseradish with time, and the distribution was found to be different at different growth stages. (141)Ce (III) can enter the mesophyll cells via apoplast and symplast channels or via plasmodesmata. (141)Ce (III) can disturb the metabolism of macronutrients in horseradish.

Validation of IC-VIEW fluorescence videography in a rabbit model of mesenteric ischaemia and reperfusion.

BACKGROUND/AIMS: Mortality in mesenteric ischaemia can be reduced by an optimised extent of resection. Up to now, no technique supplementing a surgeon's experience has achieved clinical acceptance. Besides a qualitative interpretation, the new technique of computer-assisted laser-fluorescence videography affords quantification of staining intensities. The aim of this study was to investigate the scientific value of this technique in mesenteric ischaemia in a rabbit model of controlled mesenteric ischaemia and reperfusion. METHODS: We used an established rabbit model of mesenteric ischaemia (group I, n=6) and reperfusion (group II, n=6). In each animal, three loops (each of 10 cm) of the small intestine were clamped (group I, 40 min; group II, 60 and 20 min reperfusion). For further evaluation, all loops were divided into five segments of 2 x 2 cm (total number of investigated areas, n=180). Measurement of vascular patency was performed by laser-fluorescence videography (pixel intensity per second). As standard, we used radioactive microspheres (impulse per minute per gram). In addition, the extent of ischaemic tissue damage was identified by histological examination. Statistical data were analysed by using regression analysis to define the regression coefficient r. RESULTS/FINDINGS: Laser-fluorescence videography and the microsphere technique demonstrated a close and linear correlation: ischaemic segments, r=0.90+/-0.07; reperfusion segments, r=0.85+/-0.02; overall, r=0.92+/-0.07. There was no reproducible correlation to cellular damage in histology. INTERPRETATION/CONCLUSION: Computer-assisted laser-fluorescence videography is a feasible, reliable, and valid experimental method for the detection of mesenteric blood supply and intestinal microcirculation. Clinical application is conceivable in mesenteric ischaemia and infarction as well as the operative transposition of intestine. As limiting values to identify the irreversible necrosis are not yet defined, further studies have to analyse the clinical impact more precisely.

Deposition of (90)YPO(4) and (144)CePO(4) radioisotopes on polymer surfaces for radiation delivery devices.

Intravascular irradiation with beta emitters inhibits restenosis in arteries after balloon angioplasty or stent implantation. Yttrium-90 ((90)Y, T(1/2)=64 h) and cerium-144 ((144)Ce, T(1/2)=286 d) emit beta particles (E(max)=2.28--3.50 MeV) having an ideal energy range for brachytherapy delivery system. In this article, a previously reported method for depositing (32)P on poly(ethylene terephtalate) (PET) surfaces is generalized and modifications that allow deposition of other beta-emitting radioisotopes, such as (90)Y and (144)Ce, are demonstrated. PET films were first coated with chitosan hydrogel and then adsorbed different amounts of phosphoric acid (PA) in aqueous solutions. Yttrium was deposited onto the surface as YPO(4) after the films were immersed in YCl(3) solutions. 1 muCi (90)YCl(3) (2 x 10(-9) g) was used in each sample as a tracer for measuring the deposition efficiency, which is defined as the percentage of YCl(3) deposited on the surface compared to the amount of YCl(3) in solutions before the deposition. In order to improve the safety of brachytherapy treatments, polyurethanes were used to seal the deposited radioisotopes on the surface to minimize the leakage of the isotopes into the patients. The generality of this method presented here for a wide variety of particular radioisotopic components allows design of a broad range of versatile radioisotope sources.

The placental transfer of cerium: experimental studies and estimates of doses to the human fetus from 141Ce and 144Ce.

PURPOSE: To measure the transfer of cerium from mother to fetus in experimental animals and estimate doses to the human fetus following intakes of radioisotopes of Ce. MATERIALS AND METHODS: Cerium-141 in chloride solution was administered intravenously to rats at different stages of pregnancy (days 9.5, 12.5 or 18.5), and retention in the embryo/fetus and associated tissues was measured 3 days later in each case. Retention in rat fetal tissues on day 21.5 (shortly before birth) was also measured after administration of 141Ce chloride 1 month prior to conception or 141Ce citrate on day 18.5. Cerium-141 chloride was administered to guinea pigs on day 50 for measurements of fetal retention on day 57 (shortly before birth). RESULTS: Retention of 141Ce in the rat embryo/fetus, measured at 3 days after administration to the mother, increased from about 0.00002% of injected activity per embryo/fetus on day 12.5 to about 0.014% on day 21.5 of gestation. However, the relative concentrations of 141Ce in the embryo/fetus and mother (CF:CM ratio) were between 0.005 and 0.01 in each case. After 141Ce administration prior to conception, retention by the rat fetus on day 21.5 was substantially lower than after short-term administration. Comparison of retention of 141Ce on day 21.5 after administration on day 18.5 as either chloride or citrate showed similar levels in maternal tissues but greater transfer to the fetus (CF:CM ratio of 0.03). Retention in the guinea pig fetus in late gestation at 7 days after administration of (141)Ce chloride was about 0.05% injected activity per fetus, corresponding to a CF:CM ratio of about 0.02. CONCLUSION: These results and other published animal data have been used to specify CF:CM ratios for use in the calculation of doses to the human fetus. The values used were 0.05 for intakes during pregnancy and 0.01 for intakes prior to conception. Doses to the offspring after maternal ingestion of 141Ce or 144Ce are largely due to irradiation from activity in the maternal colon and are insensitive to CF:CM. After inhalation, however, absorption of Ce to blood is much greater and doses to the offspring are dominated by the contribution from activity in the fetus, and therefore dependent on the CF:CM ratio used.

Lung albumin accumulation is spatially heterogeneous but not correlated with regional pulmonary perfusion.

The contribution of pulmonary perfusion heterogeneity to the development of regional differences in lung injury and edema is unknown. To test whether regional differences in pulmonary perfusion are associated with regional differences in microvascular function during lung injury, pigs were mechanically ventilated in the prone position and infused with endotoxin (Escherichia coli 055:B5, 0.15 microg. kg(-1). h(-1); n = 8) or saline (n = 4) for 4 h. Extravascular albumin accumulation and perfusion were measured in multiple approximately 0.7-ml lung regions by injecting pigs with radiolabeled albumin and radioactive microspheres, respectively. Extravascular albumin accumulation was spatially heterogeneous but not correlated with regional perfusion. Extravascular albumin accumulation was greater in dorsal than ventral regions, and regions with similar albumin accumulation were spatially clustered. This spatial organization was less evident in endotoxemic than control pigs. We conclude that there are regional differences in lung albumin accumulation that are spatially organized but not mediated by regional differences in pulmonary perfusion. We speculate that regional differences in microvascular pressure or endothelial function may account for the observed distribution of extravascular albumin accumulation.

Study on the kinetics of cerium(III) adsorption-desorption on different soils of China.

The kinetics of Ce(III) adsorption-desorption on four typical soils in China has been studied by using the batch method with the radioactive nuclide 141Ce. Results indicated that Ce(III) adsorption was rapid and nearly finished in less than 0.5 min. Desorption procedure was about completed in 1-30 min in the tested soils. Ce(III) desorption equilibrium times vary with different soils. The amounts of Ce(III) desorption on different soils in the same time were different. The Elovich equation proved to be the best models for fitting the data of Ce(III) desorption reactions in fluvo-aquic soil and black soil; and the parabolic-diffusion equation was the best model in red earth and loess soil.