Publications by authors named "Elise Levigoureux"

7 Publications

  • Page 1 of 1

Radiochemical purity of technetium-99m-nanocolloid rhenium sulphide is not influenced by heating.

Nucl Med Commun 2019 Jun;40(6):565-567

Radiopharmacy Unit, Departement of Pharmacy, Groupement Hospitalier Est, Hospices Civils de Lyon, 59 boulevard Pinel, 69677 Bron Cedex.

Despite a mistake during the preparation of technetium-99m (Tc)-nanocolloid rhenium sulphide (Nanocis) because of lack of heating, the apparent radiochemical purity (RCP) of this product was correct. The objectives of this study were to evaluate the impact of absence of heating on the RCP of Tc-nanocolloid rhenium sulphide and the effect of heating on particle size. Five Tc-Nanocis were prepared according to the manufacturer's instructions and five others were realized without any heating step. Quality controls were performed for each preparation. To evaluate the effect of heating on particle size, preparations were filtered through a 0.22 µm sterilizing membrane filter before and after 30 min of heating. The radioactivity was measured before and after the filtration. The results showed that absence of heating does not influence the apparent RCP of Tc-nanocolloid of rhenium sulphide. In terms of the particle size, 72% of particles had a diameter less than 0.22 µm before heating, as opposed to 21% after heating. To conclude, this study underlines a problem of quality control of the Tc-nanocolloid rhenium sulphide preparation, which cannot detect a lack of heating and can lead to the release of preparations that would not be suitable for scintigraphy.
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http://dx.doi.org/10.1097/MNM.0000000000000988DOI Listing
June 2019

Serotonin 5-HT Receptor Biased Agonists Induce Different Cerebral Metabolic Responses: A [F]-Fluorodesoxyglucose Positron Emission Tomography Study in Conscious and Anesthetized Rats.

ACS Chem Neurosci 2019 07 7;10(7):3108-3119. Epub 2019 Jan 7.

Université de Lyon, Université Claude Bernard Lyon 1 , Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028 , Lyon 69677 , France.

Serotonin 5-HT receptors constitute an attractive therapeutic target for various psychiatric or neurodegenerative disorders. These receptors are expressed in multiple brain regions on different neuronal populations and can be coupled with distinct G-protein subtypes; such functional diversity complicates the use of 5-HT ligands in several pathologies where it would be desirable to stimulate the receptors in a precise region. Therefore, using "biased agonists" able to target specifically certain subpopulations of 5-HT receptors would enable achievement of better therapeutic benefit. Several 5-HT receptor biased agonists are currently in development, including NLX-101 (aka F15599) and NLX-112 (aka F13640, befiradol), with preclinical data suggesting that they preferentially target different populations of 5-HT receptors. However, most previous studies used invasive and regionally limited approaches. In this context, [F]-fluorodesoxyglucose (FDG)-positron emission tomography (PET) imaging constitutes an interesting technique as it enables noninvasive mapping of the regional brain activity changes following a pharmacological challenge in conscious animals. We report here the evaluation of cerebral glucose metabolism following intraperitoneal injection of different doses of NLX-112 or NLX-101 in conscious or isoflurane-anesthetized rats. The biased agonists produced different metabolic "fingerprints" with distinct regional preferences, consistent with previous studies. At equal doses, the effect of NLX-101 was less marked than NLX-112 in the piriform cortex, in the striatum (in terms of inhibition), and in the pontine nuclei and the cerebellum (in terms of activation); furthermore, only NLX-112 increased the glucose metabolism in the parietal cortex, whereas only NLX-101 induced a clear activation in the colliculi and the frontal cortex, which may be related to its distinctive procognitive profile. Both agonist effects were almost completely unapparent in anesthetized animals, underlining the importance of studying serotonergic neurotransmission in the conscious state. In this regard, [F]FDG-PET imaging seems very complementary with other functional imaging techniques such as pharmacological MRI.
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http://dx.doi.org/10.1021/acschemneuro.8b00584DOI Listing
July 2019

In Silico, in Vitro, and in Vivo Evaluation of New Candidates for α-Synuclein PET Imaging.

Mol Pharm 2018 08 25;15(8):3153-3166. Epub 2018 Jul 25.

Université de Lyon, Université Claude Bernard Lyon 1, Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028 , Lyon 69361 , France.

Accumulation of α-synuclein (α-syn) is a neuropathological hallmark of synucleinopathies. To date, no selective α-syn positron emission tomography (PET) radiotracer has been identified. Our objective was to develop the first original, selective, and specific α-syn PET radiotracer. Chemical design inspired from three structural families that demonstrated interesting α-syn binding characteristics was used as a starting point. Bioinformatics modeling of α-syn fibrils was then employed to select the best molecular candidates before their syntheses. An in vitro binding assay was performed to evaluate the affinity of the compounds. Radiotracer specificity and selectivity were assessed by in vitro autoradiography and in vivo PET studies in animal (rodents) models. Finally, gold standard in vitro autoradiography with patients' postmortem tissues was performed to confirm/infirm the α-syn binding characteristics. Two compounds exhibited a good brain availability and bound to α-syn and Aβ fibrils in a rat model. In contrast, no signal was observed in a mouse model of synucleinopathy. Experiments in human tissues confirmed these negative results.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00229DOI Listing
August 2018

PET imaging of the influence of physiological and pathological α-synuclein on dopaminergic and serotonergic neurotransmission in mouse models.

CNS Neurosci Ther 2019 01 20;25(1):57-68. Epub 2018 May 20.

Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.

Aims: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83).

Methods: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([ F]FDG), dopamine neurotransmission ([ C]raclopride, [ C]PE2I) and serotonin neurotransmission ([ F]MPPF, [ C]DASB). For all radiotracers, except [ F]FDG, PET data were analyzed with a MRI-based VOI method and a voxel-based analysis.

Results: MicroPET data showed a decrease in [ C]raclopride uptake in the caudate putamen of KO α-syn mice, in comparison with M83 and WT mice, reflecting a lower concentration of D receptors. The increase in [ F]MPPF uptake in M83 vs WT and KO mice indicates overexpression of 5-HT receptors. The lack of change in dopamine and serotonin transporters in all groups suggests unchanged neuronal density.

Conclusions: This PET study highlights an effect of α-syn modulation on the expression of the D receptor, whereas aggregated α-syn leads to overexpression of 5-HT receptor, as a pathophysiological signature.
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http://dx.doi.org/10.1111/cns.12978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436587PMC
January 2019

Amyloid-Beta Radiotracer [F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue.

Contrast Media Mol Imaging 2018 6;2018:9165458. Epub 2018 Feb 6.

Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.

The accumulation of aggregated alpha-synuclein (-syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated -syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy. One Positron Emission Tomography (PET) study suggested [C]BF-227 as a promising radiotracer for monitoring intracellular -syn deposition in MSA patients. We sought to confirm the binding of this radiotracer to -syn using state-of-the-art autoradiography. Medulla sections were obtained from 9 MSA patients and 9 controls (London Neurodegenerative Diseases Brain Bank). [F]BF-227, chemically identical to [C]BF-227, was used at nanomolar concentrations to perform autoradiography assays. Autoradiograms were superimposed on fluorescent staining from the conformational anti--syn antibody 5G4 and quantified after immunofluorescence-driven definition of regions of interest. Autoradiography showed no specific signals in MSA patients in comparison to controls despite widespread pathology detected by immunofluorescence. Autoradiography does not support a significant binding of [F]BF-227 to CGI at concentrations typically achieved in PET experiments.
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http://dx.doi.org/10.1155/2018/9165458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818909PMC
July 2019

Binding of the PET radiotracer [¹⁸F]BF227 does not reflect the presence of alpha-synuclein aggregates in transgenic mice.

Curr Alzheimer Res 2014 ;11(10):955-60

CERMEP-Imaging Platform, 59 boulevard Pinel, Lyon, F-69003, France.

Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of many neurodegenerative diseases, collectively termed synucleinopathies. There is currently no pre-mortem diagnosis tool for these diseases. Although some compounds have been described as potential ligands for α-syn aggregates, no specific PET radiotracer of aggregated α-syn is currently available. Recently, [(18)F]BF227 has been proposed as an α-syn PET radiotracer in the absence of other specific candidates. We proposed here, for the first time, to use this radiotracer in an accelerated mouse model of synucleinopathy presenting α-syn depositions in brainstem and thalamus. Our in vivo and in vitro studies showed that [(18)F]BF227 does not bind to α-syn aggregates. These results highlight the fact that [(18)F]BF227 PET has no suitable characteristics for monitoring this experimental synucleinopathy, justifying the need to develop alternative α-syn PET radiotracers.
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http://dx.doi.org/10.2174/1567205011666141107154201DOI Listing
August 2015

A multi-atlas based method for automated anatomical rat brain MRI segmentation and extraction of PET activity.

PLoS One 2014 17;9(10):e109113. Epub 2014 Oct 17.

CERMEP - Imagerie du Vivant, Lyon, France.

Introduction: Preclinical in vivo imaging requires precise and reproducible delineation of brain structures. Manual segmentation is time consuming and operator dependent. Automated segmentation as usually performed via single atlas registration fails to account for anatomo-physiological variability. We present, evaluate, and make available a multi-atlas approach for automatically segmenting rat brain MRI and extracting PET activies.

Methods: High-resolution 7T 2DT2 MR images of 12 Sprague-Dawley rat brains were manually segmented into 27-VOI label volumes using detailed protocols. Automated methods were developed with 7/12 atlas datasets, i.e. the MRIs and their associated label volumes. MRIs were registered to a common space, where an MRI template and a maximum probability atlas were created. Three automated methods were tested: 1/registering individual MRIs to the template, and using a single atlas (SA), 2/using the maximum probability atlas (MP), and 3/registering the MRIs from the multi-atlas dataset to an individual MRI, propagating the label volumes and fusing them in individual MRI space (propagation & fusion, PF). Evaluation was performed on the five remaining rats which additionally underwent [18F]FDG PET. Automated and manual segmentations were compared for morphometric performance (assessed by comparing volume bias and Dice overlap index) and functional performance (evaluated by comparing extracted PET measures).

Results: Only the SA method showed volume bias. Dice indices were significantly different between methods (PF>MP>SA). PET regional measures were more accurate with multi-atlas methods than with SA method.

Conclusions: Multi-atlas methods outperform SA for automated anatomical brain segmentation and PET measure's extraction. They perform comparably to manual segmentation for FDG-PET quantification. Multi-atlas methods are suitable for rapid reproducible VOI analyses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109113PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201469PMC
July 2015