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Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET
No full textPBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[18F]F-Kryptofix 222 and 6.8-7.6 μ mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [18F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/μ mol (2-4 Ci/μ mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). © 2008 John Wiley & Sons, Ltd
Blue carbon oxidation revealed by radiogenic and stable isotopes in a mangrove system
No full textMangroves are among the most carbon-rich ecosystems on Earth and can sequester carbon in sediments over long timescales. Here we assess whether century-old buried carbon may be remineralized and exported by measuring Δ14C in the exported dissolved inorganic carbon (DIC) as well as sediment Δ14C profiles in a subtropical mangrove. Pore water exchange released isotopically depleted, old DIC to surface waters. Keeling plots revealed that the source of DIC to surface waters had a δ13C-DIC value of −29.4 ±1.9‰ and Δ14C-DIC value of −73±9‰. The respired and exported carbon comes from an average depth of ~40 cm, equivalent to ~100 years of sediment accumulation. Therefore, century-old sequestered carbon is still susceptible to remineralization and tidal export to the coastal ocean via pore water exchange or submarine groundwater discharge. We suggest that the timescales over which blue carbon burial is assessed should consider carbon losses via pore water exchange. © 2017. American Geophysical Unio
β-Amyloid is associated with aberrant metabolic connectivity in subjects with mild cognitive impairment
No full textPositron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer's disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein E ɛ4 (APOE ɛ4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ɛ4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ɛ4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns. © 2014 International Society for Cerebral Blood Flow & Metabolism, Inc
The impact of high and low dose ionising radiation on the central nervous system
No full textResponses of the central nervous system (CNS) to stressors and injuries, such as ionising radiation, are modulated by the concomitant responses of the brains innate immune effector cells, microglia. Exposure to high doses of ionising radiation in brain tissue leads to the expression and release of biochemical mediators of ‘neuroinflammation’, such as pro-inflammatory cytokines and reactive oxygen species (ROS), leading to tissue destruction. Contrastingly, low dose ionising radiation may reduce vulnerability to subsequent exposure of ionising radiation, largely through the stimulation of adaptive responses, such as antioxidant defences. These disparate responses may be reflective of non-linear differential microglial activation at low and high doses, manifesting as an anti-inflammatory or pro-inflammatory functional state. Biomarkers of pathology in the brain, such as the mitochondrial Translocator Protein 18 kDa (TSPO), have facilitated in vivo characterisation of microglial activation and ‘neuroinflammation’ in many pathological states of the CNS, though the exact function of TSPO in these responses remains elusive. Based on the known responsiveness of TSPO expression to a wide range of noxious stimuli, we discuss TSPO as a potential biomarker of radiation-induced effects. © 2016 The Authors Published by Elsevier B.V
Central nervous system expression and PET imaging of the translocator protein in relapsing–remitting experimental autoimmune encephalomyelitis
No full textGlial neuroinflammation is associated with the development and progression of multiple sclerosis. PET imaging offers a unique opportunity to evaluate neuroinflammatory processes longitudinally in a noninvasive and clinically translational manner. (18)F-PBR111 is a newly developed PET radiopharmaceutical with high affinity and selectivity for the translocator protein (TSPO), expressed on activated glia. This study aimed to investigate neuroinflammation at different phases of relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) in the brains of SJL/J mice by postmortem histologic analysis and in vivo by PET imaging with (18)F-PBR111. METHODS: RR EAE was induced by immunization with PLP(139-151) peptide in complete Freund's adjuvant. Naive female SJL/J mice and mice immunized with saline-complete Freund's adjuvant were used as controls. The biodistribution of (18)F-PBR111 was measured in 13 areas of the central nervous system and compared with PET imaging results during different phases of RR EAE. The extents of TSPO expression and glial activation were assessed with immunohistochemistry, immunofluorescence, and a real-time polymerase chain reaction. RESULTS: There was significant TSPO expression in all of the central nervous system areas studied at the peak of the first clinical episode and, importantly, at the preclinical stage. In contrast, only a few TSPO-positive cells were observed at the second episode. At the third episode, there was again an increase in TSPO expression. TSPO expression was associated with microglial cells or macrophages without obvious astrocyte labeling. The dynamics of (18)F-PBR111 uptake in the brain, as measured by in vivo PET imaging and biodistribution, followed the pattern of TSPO expression during RR EAE. CONCLUSION: PET imaging with the TSPO ligand (18)F-PBR111 clearly reflected the dynamics of microglial activation in the SJL/J mouse model of RR EAE. The results are the first to highlight the discrepancy between the clinical symptoms of EAE and TSPO expression in the brain, as measured by PET imaging at the peaks of various EAE episodes. The results suggest a significant role for PET imaging investigations of neuroinflammation in multiple sclerosis and allow for in vivo follow-up of antiinflammatory treatment strategies. © 2013 Society of Nuclear Medicine and Molecular Imaging, Inc
Cannabinoid administration increases 5HT1A receptor binding and mRNA expression in the hippocampus of adult but not adolescent rats
No full textThe endocannabinoid and serotonin systems share a high level of overlap in terms of the physiological processes that they regulate, however, little is known about their functional interactions particularly during adolescence, a vulnerable period for both the development of psychosis and for initiation to substance use. In the present study, the effects of cannabinoid treatment on serotonin 5HT1A receptor density and mRNA expression were investigated in two age groups: Adolescent (postnatal day 35) and adult (postnatal day 70) rats were injected with the synthetic cannabinoid HU210 (25, 50 or 100 μg/kg) or vehicle for 1, 4 or 14 days and sacrificed 24 h after the last injection. 5HT1A receptor density was measured in different brain regions using [3H]8-OH-DPAT quantitative autoradiography whereas mRNA expression was measured in adjacent brain sections. Higher levels of both serotonin 5HT1A receptor binding and mRNA expression were observed in limbic regions in adolescent control animals compared to adults. 5HT1A receptor density was increased by 23% in the CA1 region of the hippocampus of adult rats treated with 100 μg/kg HU210 for 4 days compared to vehicle treated controls. The same treatment increased mRNA expression by 27% and by 14% in the CA1 region and dentate gyrus of the hippocampus respectively. 5HT1A receptor density was increased by 22% in the CA1 of adult animals treated with 50 μg HU210, by 26% in the dentate gurus of adult rats treated with 100 μg for 14 days. By contrast, 5HT1A receptor density or mRNA expression was not affected in the brain of adolescent animals in any of the brain regions examined. These results suggest that cannabinoid treatment has differential effects on serotonin-related neurochemistry in adolescent compared to adult rats. The effects in the adult brain may compromise hippocampal function and could account for the cognitive deficits seen in habitual heavy cannabis users. © 2010 IBR
Structural studies of the rhombohedral and orthorhombic monouranates: CaUO4, α-SrUO4, β-SrUO4 and BaUO4
No full textThe structures of some AUO4 (A=Ca, Sr, or Ba) oxides have been determined using a combination of neutron and synchrotron X-ray diffraction, supported by X-ray absorption spectroscopic measurements at the U L3-edge. The smaller Ca cation favours a rhombohedral AUO4 structure with 8-coordinate UO8 moieties whilst an orthorhombic structure based on UO6 groups is found for BaUO4. Both the rhombohedral and orthorhombic structures can be stabilised for SrUO4. The structural studies suggest that the bonding requirements of the A site cation play a significant role in determining which structure is favoured. In the rhombohedral structure, Bond Valence Sums demonstrate the A site is invariably overbonded, which, in the case of rhombohedral α-SrUO4, is compensated for by the formation of vacancies in the oxygen sub-lattice. The uranium cation, with its flexible oxidation state, is able to accommodate this by inducing vacancies along its equatorial coordination site as demonstrated by neutron powder diffraction. © 2016 Elsevier Inc
One-dimensional uranium(VI) coordination polymers with pyridinecarboxylate ligands
No full textA method to produce picolinate ligand in situ under hydrothermal conditions has been used to synthesize four uranyl hydroxyl, oxo- and oxohydroxyl picolinato complexes. (UO2)(OH)(Pic) (1) (HPic = picolinic acid) contains 7-fold coordinated uranyl hydroxyl dimers linked through μ2-bridging Pic ligands forming a one-dimensional (1D) polymer. (NH4)[(UO2)3(O)2(OH)(Pic)2] (2) consists of 7-fold coordinated uranyl oxohydroxyl trinuclear units linked through both μ2- and μ3-Pic ligands forming a 1D polymer. (NH4)[(UO2)2(O)2(Pic)] (3) is constructed with 7-fold coordinated uranyl oxo-dinuclear units linked through oxo- and μ3-Pic ligands forming a 1D polymer. (NH4)[(UO2)4(O)2(OH)2(Pic)2(INT)]·H2O (4) (HINT = isonicotinic acid) is made of 7-fold coordinated uranyl oxohydroxyl tetranuclear units linked through both Pic and INT ligands forming a 1D polymer. All four polymers are thermal robust to 350 °C. Raman spectroscopy confirmed the presence of uranyl ion and Pic ligand. In addition, red enhanced fluorescence emissions have been observed for both 1 and 4. The synthesis method, with the advantage of controlling uranyl hydrolysis and generating ligand in situ, provides a more reliable way to make new coordination polymers of carboxylate ligands with various uranyl hydrolysis species. © 2016 Elsevier Ltd
Molten FLiNaK salt infiltration into degassed nuclear graphite under inert gas pressure
No full textInfiltration of molten FLiNaK salt into degassed nuclear graphite samples under inert gas pressure was studied. The weight gain of different grades (2020, 2114, IG-110, NBG-8, G1 and G2) of nuclear graphite during infiltration with different pressures was measured. Molten salt infiltration was compared with mercury intrusion porosimetry where it was found that mercury infiltration was a useful predictor of the threshold pressure and infiltration volume per gram graphite for molten salt infiltration. The distribution and morphology of salt in the graphite were observed by scanning electron microscopy, with very little difference between the molten salt content at the center and edge of samples for samples infiltrated at pressure higher than the threshold pressure. Increased molten salt infiltration with increased pressure resulted from the occupation of smaller pores and full occupation of the larger irregular pores. The similarity of weight gain between molten salt infiltration equilibrated at 20 and 100 h showed 20 h was adequate to obtain equilibrium. © 2014 Elsevier Ltd
Using in situ synchrotron x-ray diffraction to study lithium- and sodium-ion batteries: A case study with an unconventional battery electrode (Gd2TiO5)
No full textDesigning materials for application as electrodes in sodium-ion batteries may require the use of unconventional materials to realize acceptable reversible sodium insertion/extraction capabilities. To design new materials simple electrochemical methods need to be coupled with other techniques such as in situ x-ray diffraction (XRD) to correlate the influence of electrochemical performance on a parameter that can be modified, e.g., the crystal structure of the material. Here we use in situ synchrotron XRD data on Gd2TiO5-containing cells to show the minor changes in reflection positions during discharge/charge that illustrates minimal volume expansion and contraction due to insertion/extraction reactions. These small changes correlate to the Gd2TiO5 anode material in both lithium- and sodium-ion batteries showing reversible capacities of ∼45 and ∼23 mA h/g after 20 cycles, respectively. Analysis of sodium location in the crystal structure shows a preference for sodium in the smaller channels along the c axis direction during the first discharge before moving to the larger channels at the charged state. Therefore, in this work, in situ studies highlight minimal structural changes with respect to volume expansion during electrochemical cycling and illustrate where sodium ions locate within the Gd2TiO5 structure. © 2014 Materials Research Societ