Visualization of the Phase Propagation within Carbon-Free Li4Ti5O12 Battery Electrodes

The electrochemical reactions occurring in batteries involve the transport of ions and electrons among the electrodes, the electrolyte, and the current collector. In Li-ion battery electrodes, this dual functionality is attained with porous composite electrode structures that contain electronically conductive additives. Recently, the ability to extensively cycle composite electrodes of Li4Ti5O12without any conductive additives generated questions about how these structures operate, the answers to which could be used to design architectures with other materials that reduce the amount of additives that do not directly store energy. Here, the changes occurring in carbon-free Li4Ti5O12 electrodes during lithiation were studied by a combination of ex situ and operando optical microscopy and microbeam X-ray absorption spectroscopy (μ-XAS). The measurements provide visualizations of the percolation of lithiated domains through the thick (∼40-μm) structure after a depth of discharge of only 1%, followed by a second wave of propagation starting with regions in closest contact with the current collector and progressing toward regions in contact with the bulk electrode. These results emphasize the interplay between the electronic and ionic conductivities of the phases involved in a battery reaction and the formation of the phases in localized areas in the electrode architecture. They provide new insights that could be used to refine the design of these architectures to minimize transport limitations while maximizing energy density

Angiogenesis

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [Ga]Ga-AP747 and [Ga]Ga-RGD small animal PET/CT. [Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [Ga]Ga-RGD. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [Ga]Ga-AP747 PET signal was more than twice higher than that of [Ga]Ga-RGD on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [Ga]Ga-RGD.France Life Imagin

The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia

The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension1, 2, 3. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension

Pharmaceutical interviews to overcome digestive artefacts on [ 99m Tc]Tc‐tetrofosmin myocardial perfusion scintigraphy

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Molecular imaging characterization of Distraction Osteogenesis model

International audienceAim/Introduction: Distraction osteogenesis (DO) is a surgical procedure widely used for limb lengthening to treat limb length discrepancy. DO procedure is divided into three distinct phases. The latency period starts after callotasis surgery (A), followed by the distraction period (B). When the desired elongation is reached, the external fixator is then locked, and consolidation period is initiated (C). To date, if limb lengthening is efficient, the duration of phase C needed to remove external fixator, remains hard to set, causing a high risk of fracture. This work aimed to characterize, using molecular imaging, callus regeneration, angiogenesis and osteoblastic activity in rat model of DO during Phases A, B and C. Materials and Methods: A DO rat model (1) were applied to 6 male rats. Animals were weekly monitored during the phases A (6 days), B (10 days), C (6 weeks) by μCT, μTEP and μSPECT to quantify the bone density, angiogenesis and bone metabolism. Angiogenesis were longitudinally evaluated using 10±0.5 MBq of [68Ga]-RGD. PET images were acquired 1h after injection on Mediso-NanoPET-CT. Bone metabolism were longitudinally monitored using 30±1.5 MBq of [99mTc]-HMDP. Planar SPECT images were acquired 4h after injection on Mediso-NanoSPECT-CT. Quantitative region-of-interest (ROI) analysis of PET and SPECT images were performed with Vivoquant software (Invicro®) and tissue uptake values presented as ratio of fractured bone on contralateral bone (i/c).Results: Molecular imaging showed that activation of angiogenesis and osteogenesis both started on Day 6 after the surgery during PhaseA, increased progressively during Phase B up to the end of the phase to an C : i/c ratios of 5.6±1.2 and 2.59±0.4 respectively for [68Ga]-RGD and [99mTc]-HMDP imaging. Then [68Ga]-RGD TEP signal start to decrease and normalized 2 weeks after the end of phase C and [99mTc]-HMDP SPECT signal normalized 4 weeks after the end of phase C. Conclusion: This is the first report of molecular imaging characterization of DO model. DO induced strength and sustained activations of both angiogenesis and osteogenesis that persists several weeks after distraction. Osteogenesis activation is more sustained than angiogenesis. This work shows that molecular imaging can be an efficient imaging tool to evaluate new optimization of DO procedure and that PET and SPECT imaging could be a valuable tool to determine whether the bone reconstruction phase should be extended and decrease the risk of fracture for which occurrence after removal remain frequent. References: (1) M. Pithioux and al.,

Design and validation of a 68Ga-radiolabelled PET imaging agent for in vivo evaluation of angiomotin expression

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Design and validation of a 68Ga-radiolabelled PET imaging agent for in vivo evaluation of angiomotin expression

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N‐myc downstream regulated family member 1 ( <scp>NDRG1</scp> ) is enriched in myelinating oligodendrocytes and impacts myelin degradation in response to demyelination

International audienceThe N-myc downstream regulated gene family member 1 (NDRG1) is a gene whose mutation results in peripheral neuropathy with central manifestations. While most of previous studies characterized NDRG1 role in Schwann cells, the detection of central nervous system symptoms and the identification of NDRG1 as a gene silenced in the white matter of multiple sclerosis brains raise the question regarding its role in oligodendrocytes. Here, we show that NDRG1 is enriched in oligodendrocytes and myelin preparations, and we characterize its expression using a novel reporter mouse (TgNdrg1-EGFP). We report NDRG1 expression during developmental myelination and during remyelination after cuprizone-induced demyelination of the adult corpus callosum. The transcriptome of Ndrg1-EGFP+ cells further supports the identification of late myelinating oligodendrocytes, characterized by expression of genes regulating lipid metabolism and bioenergetics. We also generate a lineage specific conditional knockout (Olig1 cre/+ ;Ndrg1 fl/fl) line to study its function. Null mice develop normally, and despite similar numbers of progenitor cells as wild type, they have fewer mature oligodendrocytes and lower levels of myelin proteins than controls, thereby suggesting NDRG1 as important for the maintenance of late myelinating oligodendrocytes. In addition, when control and Ndrg1 null mice are subject to cuprizoneinduced demyelination, we observe a higher degree of demyelination in the mutants. Together these data identify NDRG1 as an important molecule for adult myelinating oligodendrocytes, whose decreased levels in the normal appearing white matter of human MS brains may result in greater susceptibility of myelin to damage

Sublingual Atropine Administration as a Tool to Decrease Salivary Glands’ PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [68Ga]Ga-PSMA-11

International audienceProstate Specific Membrane Antigen (PSMA)-directed radionuclide therapy has gained an important role in the management of advanced castration-resistant prostate cancer. Although extremely promising, the prolongation in survival and amelioration of disease-related symptoms must be balanced against the direct toxicities of the treatment. Xerostomia is amongst the most common and debilitating of these, particularly when using an alpha emitter. It is therefore of main importance to develop new preventive strategies. This preclinical study has evaluated the effect of α-adrenergic and anticholinergic drugs on [99mTc]TcO4− Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET/CT). Methods: The effects of phenylephrine, scopolamine, atropine, and ipratropium on salivary glands uptake were evaluated in non-tumor-bearing mice by [99mTc]TcO4− microSPECT/CT. The most efficient identified strategy was evaluated in non-tumor-bearing and xenografted mice by [68Ga]Ga-PSMA-11 PET/CT. Results: Scopolamine and atropine showed a significant decrease in the parotid glands’ uptake on SPECT/CT whereas phenylephrine and ipratropium failed. Atropine premedication (sublingual route), which was the most effective strategy, also showed a drastic decrease of [68Ga]Ga-PSMA-11 salivary glands’ uptake in both non-tumor-bearing mice (−51.6% for the parotids, p < 0.0001) and human prostate adenocarcinoma xenografted mice (−26.8% for the parotids, p < 0.0001). Conclusion: Premedication with a local administration of atropine could represent a simple, safe, and efficient approach for reducing salivary glands’ uptake