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The status of serotonin 5HT2A receptors (5HT2ARs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5HT2AR density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study investigates 5HT2AR density in the post-mortem prefrontal cortex from subjects with schizophrenia and controls using three radiotracers with a different pharmacological profile. The specific binding parameters of the inverse agonist [18F]altanserin, the agonist [3 H]lysergic acid diethylamide (LSD) and the antagonist [ 3 H]MDL100907 to brain cortex membranes from 20 subjects with schizophrenia and 20 individually matched controls were evaluated under similar methodological conditions. Ten schizophrenia subjects were antipsychotic-free at death. Saturation curve analyses were performed by non-linear regression to obtain a maximal density of binding sites (Bmax) and the affinity of the respective radiotracers (Kd). In schizophrenia subjects, 5-HT2AR density was decreased when quantified by [18F]altanserin binding, whereas increased when evaluated by [3 H]LSD binding. However, [3 H] MDL100907 binding was unaltered. A slight loss of affinity (higher Kd) was observed exclusively in [3 H]LSD binding. The findings were more evident in antipsychotic-free subjects than in antipsychotic-treated subjects. In conclusion, a higher proportion of the 5-HT2AR-active functional conformation, which is rather identified by agonist radiotracers, was observed in schizophrenia patients. A consequent reduction of the inactive 5-HT2AR conformation, which is preferentially identified by inverse agonist radiotracers, was also obtained. Antagonist radiotracers do not distinguish between molecular conformations of the receptor, and accordingly, the absence of changes was shown. These results are compatible with the proposed increased functional activity of brain cortical 5-HT2ARs in schizophrenia. This study was supported by the Spanish State Research Agency, Ministry of Science and ERD Funds (SAF-2009-08460, SAF-2017-88126-R, RYC-2017-22412 and CTQ-2017-87637-R), and the Basque Government (SAIOTEK S-PE13UN019 and IT-1211-19). Part of this work was conducted under the Maria de Maeztu Units of Excellence Programme (Grant MDM-2017-0720). C.M. and A.G.-B. were recipients of fellowships from the Marie Slodowska-Curie Programme (European Union’s Horizon 2020, Grant 747487) and the Basque Government predoctoral training Programme, respectively

There is an urgent clinical need for imaging of α‐synuclein (αSyn) fibrils, the hallmark biomarker for Parkinson's disease, in neurodegenerative disorders. Despite immense efforts, promising tracer candidates for nuclear imaging of αSyn are rare. Diphenyl pyrazoles are known modulators of αSyn aggregation and thus bear potential for non‐invasive detection of this biomarker in vivo. Here we demonstrate high‐affinity binding of the family member anle253b to fibrillar αSyn and present a high‐yielding site‐selective radiosynthesis route for 11C radiolabeling using in‐situ generated [11C]formaldehyde and reductive methylation. Radio‐HPLC of the tracer after incubation with rat serum in vitro shows excellent stability of the molecule. Positron emission tomography in healthy animals is used to assess the pharmacokinetics and biodistribution of the tracer, showing good penetration of the blood–brain barrier and low background binding to the non‐pathological brain., High binding, low background: Development of radiotracers for α‐synuclein has proven challenging. Herein we describe a radiolabeling strategy for the aggregation modulator anle253b (2) and demonstrate its successful penetration of the blood‐brain barrier in healthy rats as well as its high‐affinity binding to aggregated α‐synuclein in vitro.

There is a need for versatile in vivo nuclear imaging reporter systems to foster preclinical and clinical research. We explore the applicability of the SNAPTag and novel radiolabeled small-molecule ligands as a versatile reporter gene system for in vivo nuclear imaging. SNAPTag is a high-affinity protein tag used in a variety of biochemical research areas and based on the suicide DNA repair enzyme O6-methylguanine methyl transferase (MGMT). Its ligands are well suited for reporter gene imaging as the benzyl guanine core scaffold can be derivatized with fluorescent or radiolabeled moieties for various applications. Three guanine-based SNAPTag ligands ([18F]FBBG, [18F]pFBG and [18F]mFBG) were synthesized in high yields and were (radio)chemically characterized. HEK293 cells were engineered to express the SNAPTag on the cell surface and served as cell model to assess target affinity by radiotracer uptake assays, Western blotting and SDS-PAGE autoradiography. A subcutaneous HEK293-SNAPTag xenograft model in immunodeficient mice was used for in vivo evaluation of [18F]FBBG and [18F]pFBG while the biodistribution of [18F]mFBG was characterized in naïve animals. The results were validated by ex vivo biodistribution studies and immunofluorescence staining of the xenografts. All three radiotracers were produced in high radiochemical purity, molar activity and good yields. Western blot analysis revealed successful SNAPTag expression by the transfected HEK293 cells. In vitro testing revealed high target affinity of all three tracers with an up to 191-fold higher signal in the HEK293-SNAPTag cells compared to untransfected cells. This was further supported by a prominent radioactive protein band at the expected size in the SDS-PAGE autoradiograph of cells incubated with [18F]FBBG or [18F]pFBG. The in vivo studies demonstrated high uptake in HEK293-SNAP xenografts compared to HEK293 xenografts with excellent tumor-to-muscle ratios (7.5 ± 4.2 for [18F]FBBG and 10.6 ± 6.2 for [18F]pFBG). In contrast to [18F]pFBG and its chemical analogue [18F]mFBG, [18F]FBBG showed no signs of unspecific bone uptake and defluorination in vivo. Radiolabeled SNAPTag ligands bear great potential for clinical applications such as in vivo tracking of cell populations, antibody fragments and targeted radiotherapy. With excellent target affinity, good stability, and low non-specific binding, [18F]FBBG is a highly promising candidate for further preclinical evaluation.

Radioiodine labeling of peptides and proteins is routinely performed by using various oxidizing agents such as Chloramine T, Iodobeads, and Iodogen reagent and radioactive iodide (I−), although some other oxidizing agents were also investigated. The main objective of the present study was to develop and test a novel reagent, inorganic monochloramine (NH2Cl), for radioiodine labeling of new chemical entities and biomolecules which is cost-effective, easy to make and handle, and is selective to label amino acids, peptides, and proteins. The data presented in this report demonstrate that the yields of the non-radioactive iodine labeling reactions using monochloramine are >70% for an amino acid (tyrosine) and a cyclic peptide (cyclo Arg-Gly-Asp-d-Tyr-Lys, cRGDyK). No evidence of the formation of N-chloro derivatives in cRGDyK was observed, suggesting that the reagent is selective in iodinating the tyrosine residue in the biomolecules. The method was successfully translated into radioiodine labeling of amino acid, a peptide, and a protein, Bovine Serum Albumin (BSA).

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

There is currently great interest in the development of cell-based therapies, particularly those focused on the idea of exploiting systemically administered immune cells for therapeutic purposes in cancer (e.g., CAR-T and CAR-NK cells). The ability to monitor the fate of cells in vivo after administration is vital for the assessment of therapeutic outcomes of immune cell-based therapies both in preclinical research and clinical practice. In this context, imaging techniques, which allow for noninvasive and real-time monitoring of the distribution and long-term viability of the adoptively transferred immune cells in the tissue of interest, are of paramount importance. Among clinically relevant in vivo imaging modalities, the nuclear imaging techniques, comprising planar scintigraphy, SPECT, and PET, are considered to be of pivotal importance to in vivo cell tracking and designing optimal treatment strategies for cell-based therapies. This review paper focuses on nuclear imaging and its role in the evaluation of immune cell-based therapies’ effectiveness - tracking cells and their ability to home to the target tissue. We compare different types of radiotracers, outline various ways of immune cell labeling, and provide the latest examples for the use of nuclear imaging techniques both in preclinical studies and clinical settings.

Target-specific biomolecules, monoclonal antibodies (mAb), proteins, and protein fragments are known to have high specificity and affinity for receptors associated with tumors and other pathological conditions. However, the large biomolecules have relatively intermediate to long circulation half-lives (>day) and tumor localization times. Combining superior target specificity of mAbs and high sensitivity and resolution of the PET (Positron Emission Tomography) imaging technique has created a paradigm-shifting imaging modality, ImmunoPET. In addition to metallic PET radionuclides, 124I is an attractive radionuclide for radiolabeling of mAbs as potential immunoPET imaging pharmaceuticals due to its physical properties (decay characteristics and half-life), easy and routine production by cyclotrons, and well-established methodologies for radioiodination. The objective of this report is to provide a comprehensive review of the physical properties of iodine and iodine radionuclides, production processes of 124I, various 124I-labeling methodologies for large biomolecules, mAbs, and the development of 124I-labeled immunoPET imaging pharmaceuticals for various cancer targets in preclinical and clinical environments. A summary of several production processes, including 123Te(d,n)124I, 124Te(d,2n)124I, 121Sb(α,n)124I, 123Sb(α,3n)124I, 123Sb(3He,2n)124I, natSb(α, xn)124I, natSb(3He,n)124I reactions, a detailed overview of the 124Te(p,n)124I reaction (including target selection, preparation, processing, and recovery of 124I), and a fully automated process that can be scaled up for GMP (Good Manufacturing Practices) production of large quantities of 124I is provided. Direct, using inorganic and organic oxidizing agents and enzyme catalysis, and indirect, using prosthetic groups, 124I-labeling techniques have been discussed. Significant research has been conducted, in more than the last two decades, in the development of 124I-labeled immunoPET imaging pharmaceuticals for target-specific cancer detection. Details of preclinical and clinical evaluations of the potential 124I-labeled immunoPET imaging pharmaceuticals are described here.

The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine‐based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo‐irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution., PET tracer: A pseudo‐irreversible butyrylcholinesterase inhibitor with prolonged duration of action, high inhibitory potency and pronounced selectivity was used to design an 18F‐labeled radiotracer for positron emission tomography. Syntheses and a new protecting group strategy for radiolabeling carbamates are presented, binding and kinetics are investigated, and the radiotracer is tested in ex vivo autoradiography and in vivo microPET studies.

The marine trace gas dimethylsulfide (DMS) is the single most important biogenic source of atmospheric sulfur, accounting for up to 80% of global biogenic sulfur emissions. Approximately 300 million tons of DMS are produced annually, but the majority is degraded by microbes in seawater. The DMS precursor dimethylsulfoniopropionate (DMSP) and oxidation product dimethylsulphoxide (DMSO) are also important organic sulfur reservoirs. However, the marine sinks of dissolved DMSO remain unknown. We used a novel combination of stable and radiotracers to determine seasonal changes in multiple dissolved organic sulfur transformation rates to ascertain whether microbial uptake of dissolved DMSO was a significant loss pathway. Surface concentrations of DMS ranged from 0.5 to 17.0 nM with biological consumption rates between 2.4 and 40.8 nM&middot, d&minus, 1. DMS produced from the reduction of DMSO was not a significant process. Surface concentrations of total DMSO ranged from 2.3 to 102 nM with biological consumption of dissolved DMSO between 2.9 and 111 nM&middot, 1. Comparisons between 14C2-DMSO assimilation and dissimilation rates suggest that the majority of dissolved DMSO was respired (&gt, 94%). Radiotracer microbial consumption rates suggest that dissimilation of dissolved DMSO to CO2 can be a significant loss pathway in coastal waters, illustrating the significance of bacteria in controlling organic sulfur seawater concentrations.

Coastal sediment redeposition after resuspension events may change the sediment capacity to sequester pollutants after the formation of new sediment-water interfaces. To test this hypothesis, radiotracer experiments were performed to evaluate zinc (65Zn) and cadmium (109Cd) removal kinetics by redeposited mangrove sediments. After 24-h experiments, average inventories within redeposited sediments were close to those from control sediments (~ 20% lower in redeposited sediments), while average decreases of 41% (109Cd) and 27% (65Zn) in the half-removal times (t1/2) from overlying water were promoted by redeposited sediments in comparison with control sediments. High variability in metal removal rates, however, implied in no statistically significant differences between t1/2 values, suggesting a low influence of sediment redeposition on the metal removal capacity of mangrove sediments. More limited depth diffusion of metals was observed within redeposited sediments, always within the uppermost centimeter. Possible benefits to water quality by a slightly faster metal diffusion into redeposited sediments may be less effective due to this trend since the metal retention very close to the sediment top can facilitate new remobilization to the overlying water.

[Tc-99m][TcN-DBODC(5) is the lead candidate of a class of cationic complexes proposed as myocardial imaging agents (MPIAs). Phase I clinical studies showed that its clinical properties were comparable to those of the commercially available agents. Thus, modification of [Tc-99m]TcN-DBODC(5), directed to obtain an ideal myocardial imaging without interference from the adjacent organ activities, is desirable. This work describes the pharmacological and pharmacokinetic development of four new complexes of general formula [Tc-99m][Tc(N)(DASD)(PNPn)](+), [Tc-99m]TcN-DASD(n) (DASD = 1,4-dioxa-8-azaspiro[4,5]decandithiocarbamate; PNPn = bisphosphinoamine), proposed as improved MPIAs. Among the tested compounds, [Tc-99m]TcN-DASD(5) and [Tc-99m]TcN-DASD(7) showed enhanced heart uptake compared with the gold standards, with a rapid liver washout and superior heart-to-liver ratio. These features might shorten the duration of imaging procedures below 30 min, consenting the early acquisition of high-quality images. In addition, mechanistic studies were performed in cellulo by using human drug-sensitive and drug-resistant cancer cell lines, obtaining results which might be conveniently applied to tumor imaging.

Cadmium is a serious environmental pollutant and its uptake by plant represents a serious health risk. Uptake, accumulation as well as sensitivity of soybean plants to metals have been shown to vary with genotype, while the dynamics of this uptake has rarely been studied. Here we studied the uptake and accumulation of Cd2+ ions in different parts of soybean plants of four cultivars Moravians, Gallec, Kent and Cardiff. The plants at early developmental stage were immersed in Hoagland nutrient solution in the presence or absence of 50 mg.L−1 and the isotope of 109Cd2+ to monitor its accumulation continuously at 24 h intervals for 10 days. Our results showed that the uptake rate varied among the cultivars, being the highest in roots of the cv. Moravians and the lowest in the cv. Gallec. We also observed a non-even distribution of radioactivity within the entire plants of individual cultivars. The most of Cd2+ isotope was translocated into primary leaves and leaves in the cvs. Kent and Moravians; on the contrary, relatively less in the cvs. Cardiff and Gallec. The results were fitted with genetic potential, growth as well as defense parameters such as proline accumulation. Combining uptake dynamics and biochemical data are indicative for different tolerance strategies of soybeans.

Atherosclerosis is a well-known disease leading to cardiovascular events, including myocardial infarction and ischemic stroke. These conditions lead to a high mortality rate, which explains the interest in their prevention, early detection, and treatment. Molecular imaging is able to shed light on the basic pathophysiological processes, such as inflammation, that cause the progression and instability of plaque. The most common radiotracers used in clinical practice can detect increased energy metabolism (FDG), macrophage number (somatostatin receptor imaging), the intensity of cell proliferation in the area (labeled choline), and microcalcifications (fluoride imaging). These radiopharmaceuticals, especially FDG and labeled sodium fluoride, can predict cardiovascular events. The limitations of molecular imaging in atherosclerosis include low uptake of highly specific tracers, possible overlap with other diseases of the vessel wall, and specific features of certain tracers’ physiological distribution. A common protocol for patient preparation, data acquisition, and quantification is needed in the area of atherosclerosis imaging research.

Research on the adenosine receptors has been supported by the continuous discovery of new chemical probes characterized by more and more affinity and selectivity for the single adenosine receptor subtypes (A1, A2A, A2B and A3 adenosine receptors). Furthermore, the development of new techniques for the detection of G protein-coupled receptors (GPCR) requires new specific probes. In fact, if in the past radioligands were the most important GPCR probes for detection, compound screening and diagnostic purposes, nowadays, increasing importance is given to fluorescent and covalent ligands. In fact, advances in techniques such as fluorescence resonance energy transfer (FRET) and fluorescent polarization, as well as new applications in flow cytometry and different fluorescence-based microscopic techniques, are at the origin of the extensive research of new fluorescent ligands for these receptors. The resurgence of covalent ligands is due in part to a change in the common thinking in the medicinal chemistry community that a covalent drug is necessarily more toxic than a reversible one, and in part to the useful application of covalent ligands in GPCR structural biology. In this review, an updated collection of available chemical probes targeting adenosine receptors is reported.

The prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) are identified as important targets on prostate cancer. Receptor-targeting radiolabeled imaging pharmaceuticals with high affinity and specificity are useful in studying and monitoring biological processes and responses. Two potential imaging pharmaceuticals, AMBA agonist (where AMBA = DO3A-CH2CO-G-[4-aminobenzyl]- Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2) and RM1 antagonist (where RM1 = DO3A-CH2CO-G-[4-aminobenzyl]-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2), have demonstrated high binding affinity (IC50) to GRP receptors and high tumor uptake. Antagonists, despite the poor tumor cell internalization properties, can show clearer images and pharmacokinetic profiles by virtue of their higher tumor uptake in animal models compared to agonists. For characterization, development, and translation of a potential imaging pharmaceutical into the clinic, it must be evaluated in a series of tests, including in vitro cell binding assays, in vitro buffer and serum stability studies, the biodistribution of the radiolabeled material, and finally imaging studies in preclinical animal models. Data related to acetate buffer, mouse, canine, and human sera stability of 177Lu-labeled RM1 are presented here and compared with the acetate buffer and sera stability data of AMBA agonist. The samples of 177Lu-labeled RM1 with a high radioconcentration degrade faster than low-radioconcentration samples upon storage at 2&ndash, 8 &deg, C. Addition of stabilizers, ascorbic acid and gentisic acid, improve the stability of 177Lu-labeled RM1 significantly with gentisic acid being more efficient than ascorbic acid as a stabilizer. The degradation kinetics of 177Lu-labeled AMBA and RM1 in sera follow the order (fastest to slowest): mouse &gt, canine &gt, human sera. Finally, 177Lu-labeled RM1 antagonist is slower to degrade in mouse, canine, and human sera than 177Lu-labeled AMBA agonist, further suggesting that an antagonist is a more promising candidate than agonist for the positron emission tomography (PET) imaging and therapy of prostate cancer patients.

ABC transporters at the human blood-brain barrier protect the brain against the entry of harmful compounds but may also limit (or prevent) the cerebral entry of therapeutic drugs (e.g. anti-epileptics, antidepressants and antipsychotics). The efflux function of these transporters may be impaired in neurodegenerative disorders like Alzheimer and Parkinson disease. For such reasons, there is much interest in modulation of the efflux function of ABC transporters and in the monitoring of this function with positron emission tomography (PET). The efflux function of P-glycoprotein, an important member of the ABC transporter family, can be quantified with the PET tracer (R)-[ 11 C]verapamil, but the lipophilicity of this probe and the formation of radioactive metabolites which enter the brain complicate such measurements considerably. (R)-[ 11 C]verapamil is also not very suitable for the detection of P-gp upregulation, as may occur in epilepsy or drug resistance. Current radiochemical efforts are therefore focused on the development of PET probes with improved characteristics, for example; capability to detect both up- and down regulation of transporter function and expression, a better metabolic profile (no brain-entering metabolites), reduced lipophilicity and a longer physical half-life (labeling with 18 F instead of 11 C).

The biological activity influence on the mangrove sediment capacity to remove 65Zn and 109Cd from tidal water was evaluated in a site chronically polluted. Benthic Activity Indexes (BAI), corresponding to relative estimates of biological impact on radiotracer accumulation, were higher for 109Cd (~ 38%) than for 65Zn (~ 10%) in the top centimetre of sediment. However, BAI exceeded 96% for deeper sediment layers. This apparent decrease in radiotracer diffusion into deep sediments through biological activity inhibition is stronger than reported for much less polluted mangrove nearby, suggesting that benthic organisms tolerant of chronic metal pollution may affect metal sorption mechanisms.

Biodynamic modeling was used to investigate the uptake and bioaccumulation of arsenic and silver from water and food by two Hydropsychid caddisfly larvae: Hydropsyche siltalai and Hydropsyche pellucidula. Radiotracer techniques determined the uptake rate constants of arsenic and silver from water, and assimilation efficiencies from food, and their subsequent loss rate constants after accumulation from either route. The uptake rate constants (±SE) of As and Ag from solution were 0.021±0.005 and 0.350±0.049Lg(-1)day(-1), respectively, for H. siltalai, and 0.435±0.054 and 0.277±0.021Lg(-1)day(-1), respectively, for H. pellucidula in moderately hard synthetic water at 10°C. The assimilation efficiencies (±SE) of As and Ag from radiolabeled ingested food were 46.0±7.7% and 75.7±3.6%, respectively, for H. siltalai, and 61.0±4.2% and 52.6±8.6%, respectively, for H. pellucidula. Ag, but not As, AEs were significantly different between species. The AE of Ag differed from the AE of As in H. siltalai, but not in H. pellucidula. Mean efflux rate constants after accumulation of metals from solution or food ranged from 0.039 to 0.190day(-1). The efflux rate constants of As and Ag accumulated from solution were significantly lower than those of As and Ag assimilated from ingested food in both species. Experimentally derived ku and ke values were then used to predict As and Ag tissue concentrations in hydropsychids collected from 13 UK sites, including metal-contaminated streams in Cornwall. Arsenic and silver concentrations in environmental water and food (suspended particles) samples were measured. Biodynamic models successfully predicted accumulated As and Ag concentrations in resident H. siltalai and H. pellucidula at each site. The models also showed that more than 95% of accumulated As and almost 100% of accumulated Ag in H. siltalai and H. pellucidula are derived from ingested food rather than from water.

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumours and their metastases. In fact, peptide ligands of somatostatin receptors (sst’s) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogues, which show interesting binding profiles at sst’s. In this context, it was mandatory to explore the possibility that our analogues could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogues of octreotide. Interestingly, two conjugated analogues exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 &plusmn, 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 &plusmn, 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 &plusmn, 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 &plusmn, 0.2. High amount of activity (12.73 &plusmn, 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 &plusmn, 3.3% ID/g), lungs (8.42 &plusmn, 0.8% ID/g), liver (5.81 &plusmn, 0.5% ID/g) and heart (4.70 &plusmn, 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance, however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.

This review focuses on the chemistry and application of radium isotopes to environmental monitoring, analytical, and medicinal uses. In recent years, radium has been used primarily as a tracer to study the migration of radioactive substances in environmental systems. Tracing the naturally occurring radium isotopes in mineral and water sources allows for the determination of source location, residence time, and concentrations. An understanding of the concentration of radionuclides in our food and water sources is essential to everyone’s health as alpha particle decay is highly damaging in vivo. Due to this high radiobiological effectiveness, there is increased interest in using alpha-emitting radionuclides to prepare new, therapeutic radiopharmaceutical drugs. Selected studies from the recent literature are provided as examples of these modern applications of radium isotopes.

Soil sodium, while toxic to most plants at high concentrations, can be beneficial at low concentrations, particularly when potassium is limiting. However, little is known about Na(+) uptake in this 'high-affinity' range. New information is provided here with an insight into the transport characteristics, mechanism, and ecological significance of this phenomenon. High-affinity Na(+) and K(+) fluxes were investigated using the short-lived radiotracers (24)Na and (42)K, under an extensive range of measuring conditions (variations in external sodium, and in nutritional and pharmacological agents). This work was supported by electrophysiological, compartmental, and growth analyses. Na(+) uptake was extremely sensitive to all treatments, displaying properties of high-affinity K(+) transporters, K(+) channels, animal Na(+) channels, and non-selective cation channels. K(+), NH(4)(+), and Ca(2+) suppressed Na(+) transport biphasically, yielding IC(50) values of 30, 10, and

International audience; To assess the long-term safety of a geological carbon dioxide storage site, the confining properties of the rocks sealing an underground reservoir (caprocks) and their evolution inthe presence of CO2 must be characterized. The present study consists in the measurement of the transport parameters of dissolved CO2 through low permeability carbonate-rich caprocks. The properties of interest are the effective permeability and the diffusion coefficients of carbon dioxide dissolution products in water. The impact of carbon dioxide has been evaluated when altering rock samples by diffusion of a CO2-saturated brine under reservoir thermodynamic conditions, and by comparison of the pre- and post-alteration measured values. Permeability was measured by a gas-tracing method and, to study diffusion, radioactive isotopes of carbon (14C) and hydrogen (3H) were used. Despite a porosity increase observed for all the studied samples, the low values of transport parameters, measured initially, were also measured after alteration, showing a non-catastrophic alteration of the material.

The interaction of sodium and potassium ions in the context of the primary entry of Na(+) into plant cells, and the subsequent development of sodium toxicity, has been the subject of much recent attention. In the present study, the technique of compartmental analysis with the radiotracers (42)K(+) and (24)Na(+) was applied in intact seedlings of barley (Hordeum vulgare L.) to test the hypothesis that elevated levels of K(+) in the growth medium will reduce both rapid, futile Na(+) cycling at the plasma membrane, and Na(+) build-up in the cytosol of root cells, under saline conditions (100 mM NaCl). We reject this hypothesis, showing that, over a wide (400-fold) range of K(+) supply, K(+) neither reduces the primary fluxes of Na(+) at the root plasma membrane nor suppresses Na(+) accumulation in the cytosol. By contrast, 100 mM NaCl suppressed the cytosolic K(+) pool by 47-73%, and also substantially decreased low-affinity K(+) transport across the plasma membrane. We confirm that the cytosolic [K(+)]:[Na(+)] ratio is a poor predictor of growth performance under saline conditions, while a good correlation is seen between growth and the tissue ratios of the two ions. The data provide insight into the mechanisms that mediate the toxic influx of sodium across the root plasma membrane under salinity stress, demonstrating that, in the glycophyte barley, K(+) and Na(+) are unlikely to share a common low-affinity pathway for entry into the plant cell.

Uptake of waterborne Cd, Co, Mn and Zn was determined in laboratory experiments using radiotracer techniques (Cd-109, Co-57, Mn-54 and Zn-65). Labelled Zn was mainly accumulated in the digestive gland (65%) and Co in kidneys (81%); Cd and Mn were similarly distributed in digestive gland and gills. In a complementary field study, Ag, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, and Zn were analysed in scallops collected at two stations showing different contamination levels. Digestive gland and kidneys displayed the highest concentrations. Ag, As, Cd, and Fe differed in soft tissues from the two stations, suggesting that Comptopallium radula could be a valuable local biomonitor species for these elements. Low Mn and Zn concentrations found in kidneys suggest that their content in calcium-phosphate concretions differs from the other pectinids. Preliminary risk considerations suggest that As would be the only element potentially leading to exposure of concern for seafood consumers. (c) 2007 Elsevier Ltd. All rights reserved.

A method for synthesis of radiolabelled silver nanoparticles is reported. The method is based on proton activation of silver metal powder, enriched in 107Ag, with a 30.7 MeV proton beam. At this proton energy 105gAg is efficiently created, mainly via the 107Ag(p,3n)105Cd → 105gAg reaction. 105gAg has a half-life of 41.29 days and emits easily detectable gamma radiation on decay to 105Pd. This makes it very useful as a tracing radionuclide for experiments over several weeks or months. Following activation and a period to allow short-lived radionuclides to decay, the powder was dissolved in concentrated nitric acid in order to form silver nitrate (AgNO3), which was used to synthesise radiolabelled silver nanoparticles via the process of sodium borohydride reduction. For comparison, non-radioactive silver nanoparticles were synthesised using commercially supplied AgNO3 in order to check if the use of irradiated Ag powder as a starting material would alter in any way the final nanoparticle characteristics. Both nanoparticle types were characterised using dynamic light scattering, zeta-potential and X-ray diffraction measurements, while additionally the non-radioactive samples were analysed by transmission electron microscopy and UV–Vis spectrometry. A hydrodynamic diameter of about 16 nm was determined for both radiolabelled and non-radioactive nanoparticles, while the electron microscopy on the non-radioactive samples indicated that the physical size of the metal NPs was (7.3 ± 1.4) nm., This study has been partially supported by the European Commission’s 7th Framework Programme project QualityNano under the contract agreement SP4-CAPACITIES- 2010-262163.

To study the possibility of modifying diffusional-transport properties of the poly(perfluorosulfonic) acid (Nafion-117) membrane, the silica particles were incorporated in its matrix by in situ sol-gel method. The amount of silica incorporated in the membrane samples was varied by controlling the equilibrating time of the membrane sample in solution containing fixed proportion of precursor tetraethylorthosilicate (TEOS), methanol and water. The silica contents in the membrane samples were characterized by gravimetry, energy dispersive X-ray analysis (EDXRF) and transmission electron microscopy (TEM). Differential scanning calorimetry (DSC) studies showed that there were no significant difference in transition peak temperatures of both samples (Nafion-117 and Nafion/SiO(2)) in same ionic form except that enthalpies were increased in Nafion/SiO(2) samples in all the ionic forms. The increase in enthalpy was due to higher water content in Nafion/SiO(2) as compared to Nafion-117 in given ionic form as enthalpies normalized with water content of the respective membrane were comparable. The ion-exchange capacity, water uptake capacity and ion-exchange isotherms of the Na(+) + Cs(+) and Na(+) + Ba(2+) binary systems in silica embedded membrane samples were experimentally measured using appropriate radiotracers, and compared with that of pristine Nafion-117 membrane. The specific conductivities of the membrane samples with and without silica were studied in Na(+), Cs(+) and Ba(2+) ionic forms by electrochemical impedance spectroscopy (EIS). The self-diffusion coefficients of Na(+), Cs(+) and Ba(2+) ions in the Nafion/SiO(2) were measured by the radiotracer method. It was observed from the experimentally measured specific conductivities and self-diffusion coefficients data that diffusion mobility of Cs(+) and Ba(2+) counter-ions were enhanced significantly after incorporation of SiO(2) in the Nafion-117 matrix. Contrary to this, diffusion mobility of Na(+). counter-ion decreased in Nafion/SiO(2) sample. The selectivity of Cs(+) and Ba(2+) counter-ions was reduced in Nafion/SiO(2) sample with respect to pristine Nafion-117. (C) 2011 Elsevier B.V. All rights reserved.

The present work aimed at better understanding metal and metalloid bioaccumulation in the edible Pacific blue shrimp Litopenaeus stylirostris, using both laboratory and field approaches. In the laboratory, the bioaccumulation kinetics of Ag, Cd, Co, Cr, and Zn have been investigated in shrimp exposed via seawater and food, using the corresponding gamma-emitting radiotracers (Ag-110m, Cd-109, Co-57, Cr-51, and Zn-65) and highly sensitive nuclear detection techniques. Results showed that hepatopancreas and intestine concentrated the metals to the highest extent among the blue shrimp organs and tissues. Moulting was found to play a non negligible detoxification role for Co, Cr and, to a lesser extent, Zn. Metal retention by L stylirostris widely varied (from a few days to several months), according to the element and exposure pathway considered (a given metal was usually less strongly retained when ingested with food than when it was taken up from the dissolved phase). In the field study, Ag, As, Cd, Co, Cr, Cu, Mn, Ni, and Zn were analysed in shrimp collected from a New Caledonian aquaculture pond. Metal concentrations in the shrimp muscles were generally relatively low and results confirmed the role played by the digestive organs and tissues in the bioaccumulation/storage/detoxification of metals in the Pacific blue shrimp. Preliminary risk considerations indicate that consumption of the shrimp farmed in New Caledonia is not of particular concern for human health. (C) 2010 Elsevier Ltd. All rights reserved.

Bioaccumulation of 65Zn and 109Cd by the cuttlefish Sepia officinalis L. was studied at different stages of its life cycle, i.e. in embryos, juveniles and adults, following exposures via sea water, sediments and food. Cuttlefish eggs efficiently accumulated both elements from seawater with bioconcentration factors of 79 for 65Zn and 46 for 109Cd after 11 d exposure. Most of the radiotracers were found in the capsule membrane of the eggs, demonstrating that the capsule acts as a shield to protect embryos against metals. Juveniles and adults efficiently bioconcentrated both radiotracers from seawater, with the muscular tissues containing 84% of the total 65Zn and 62% of the total 109Cd. Loss kinetics followed a single exponential function for 65Zn, while for 109Cd loss was best described by a double exponential model. Biological half-lives for elimination were ca. 2 mo for both elements. After 29 d depuration in uncontaminated seawater, 76 to 87% of the radiotracers were found in the digestive gland. For both elements, the dissolved phase can be considered as a significant source of accumulation. In an experiment with radiolabelled sediments, transfer factors were very low, even after 29 d exposure. Food-chain transfer experiments demonstrated that both juveniles and adults assimilated 65Zn and 109Cd very efficiently. Moreover, loss of ingested radiotracers was much slower than elimination of 65Zn and 109Cd taken up from seawater, indicating a very strong retention of dietary Cd and Zn by juvenile as well as by adult cuttlefish. As with direct uptake from seawater, ingested radiotracers were mainly found in the digestive gland, with fractions reaching 82% for 65Zn and 97% for 109Cd after 29 d depuration. These tracer experiments indicate that (1) food is the likely primary pathway for Zn and Cd bioaccumulation in S. officinalis, and (2) the digestive gland plays a major role in the subsequent storage and presumed detoxification of these elements regardless of the uptake pathway.

International audience; Separation of divalent cations from binary electrolyte solutions with protons was achieved by electrotransport through modified cation-exchange membranes (CEMs). The CEM modification was carried out by adsorption of polyethyleneimine on the membrane surface. Without any applied driving force, both modified and non-modified membranes exhibited a higher affinity for divalent cations. Under an electrical field, the transport number of the divalent cation decreased significantly. The apparent rate constants of the penetration of the divalent cations into the membrane were calculated on the basis of unidirectional fluxes and concentration profiles of cations within the anodic unstirred layer. The unidirectional fluxes were measured by means of the radiotracer technique. The concentration profiles were determined by numerical resolution of the Nernst-Planck electrodiffusion equations coupled with the Poisson equation for current densities lower than the limiting value.

We have designed a very accurate method of measurement of the electromigration shift of atoms in metallic films. It is based on the isotopic labelling, autoradiography and the selective counting of radioactivity through a slit. The relative error on the shift only is equal to 1%. The method has been successfully tested on electromigration in indium thin films. The mobility has been measured between 100 and 150°C where it follows the Arrhenius law: μT=3.69×10 21 exp (−2.00/kT)V −1 .cm 2 .s −1 .K Mise au point d'une methode tres precise de mesure du deplacement par electromigration, fondee sur le marquage isotopique, l'autoradiographie et le comptage de la radioactivite a travers une fente. Application a l'etude de l'electromigration de l'indium en couche mince. Mesure de la mobilite entre 100 et 150 C