47 results on '"Balasse L"'
Search Results
2. PIXSIC, a Pixelated β+-Sensitive Probe for Radiopharmacological Investigations in Rat Brain: Binding Studies with [18F]MPPF
- Author
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Balasse, L., Maerk, J., Pain, F., Genoux, A., Fieux, S., Morel, C., Gisquet-Verrier, P., Zimmer, L., and Lanièce, P.
- Published
- 2015
- Full Text
- View/download PDF
3. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response
- Author
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Bacq, A, Balasse, L, Biala, G, Guiard, B, Gardier, A M, Schinkel, A, Louis, F, Vialou, V, Martres, M-P, Chevarin, C, Hamon, M, Giros, B, and Gautron, S
- Published
- 2012
- Full Text
- View/download PDF
4. Development of a specific PET radiotracer of APJ: in vitro and in vivo evaluation in a colon adenocarcinoma model
- Author
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Louis, B., Moyon, A., Bouhlel, A., Balasse, L., Fernandez, S., Simoncini, S., Hache, G., Françoise DIGNAT-GEORGE, Garrigue, P., Guillet, B., Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EANM, and Lucas, Nelly
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2020
5. Design and validation of a 68Ga-radiolabelled PET imaging agent for in vivo evaluation of APJ expression
- Author
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Louis, B, Moyon, A, Bouhlel, A, Balasse, L, Fernandez, S, Simoncini, S., Brige, P, Souihi, C, Hache, G, Dignat-George, Francoise, Garrigue, P, Guillet, B, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Interventionnelle Expérimentale (LIIE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), European-Association-of-Nuclear-Medicine (EANM), and Lucas, Nelly
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Radiomarquage ,APJ ,imagerie ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2019
6. Novel radiolabelled neurotensin analogues containing silylated amino acid for improved neurotensin receptor-1 (NTS1) targeting
- Author
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Chastel, A, Fanelli, R, Previti, S, Vimont, D, Zanotti-Fregonara, P, Guillet, B, Garrigue, P, Balasse, L, FERNANDEZ, P, Remond, E, Hindie, E, Cavelier, F, Morgat, C, CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Houston Methodist Research Institute, Partenaires INRAE, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), European-Association-of-Nuclear-Medicine (EANM), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Radiomarquage ,neurotensine ,Acide aminé ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2019
7. Radiolabelling endothelial microvesicles and evaluating their in vivo biodistribution in healthy and ischemic mice
- Author
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Garrigue, P, Giraud, R, Moyon, A, Nail, V, Simoncini, S, Balasse, L, Fernandez, S, Bouhlel, A, Dignat-George, Francoise, Guillet, B, Sabatier, F, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), European-Association-of-Nuclear-Medicine (EANM), and Lucas, Nelly
- Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2019
8. L’atteinte cognitive est associée à une rupture de la barrière hémato-encéphalique et aux concentrations d’indoxyl sulfate dans deux modèles de maladie rénale chronique chez le rat
- Author
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Bobot, M., primary, Hache, G., additional, Fernandez, S., additional, Balasse, L., additional, Brige, P., additional, Chopinet, S., additional, Thomas, L., additional, Mckay, N., additional, Burtey, S., additional, and Guillet, B., additional
- Published
- 2019
- Full Text
- View/download PDF
9. PIXSIC, a wireless radiosensitive intracerebral probe to monitor PET radiotracers in anaesthetized and awake rat
- Author
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Balasse, L., Maerk, J., Fieux, S., Frederic Pain, Gisquet, P., Morel, C., Zimmer, L., Lanièce, P., Rayet, Béatrice, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
- Abstract
Présentation orale; Aim. In neuroscience, PET functional imaging and behavioural assays in rodents are complementary approaches, despite the fact that they are rarely associated simultaneously because general anaesthesia inherent to PET precludes behavioural studies. To address this methodological limit, we have developed a radiosensitive pixelated intracerebral probe, PIXSIC, that provides access to the combination of simultaneous observations of molecular and behavioural parameters on rodents. Material and Methods. PIXSIC proposes a novel strategy for in vivo recording of the local time-activity curves of PET radiopharmaceuticals. It relies on a sub-millimetre pixelated probe of Si (17 mm long hosting 10 pixels with dimension 200 µm x 500 µm) implanted into the brain region of interest by stereotaxic surgery. Positrons are detected by reverse-biased, high-resistivity silicon diodes. The system Aims at time-resolved high sensitivity measurements in a volume of a few mm3. The pixelated detection scheme adds "imaging" features as it allows recording of the time-activity curves in different brain regions along the probe position. PIXSIC has a compact and autonomous design based on a radiofrequency data exchange link that allows for full freedom in the animals motion and behavioural activity while limiting stress during acquisition. Results and Conclusion. The first biological validations were performed on anaesthetized rats implanted with two probes, one in the region of interest (hippocampus or striatum, according to the radiotracer) and the other one in a control region (cerebellum). We used [11C]-raclopride for dopamine D2 receptors and [18F]-MPPF for serotonin 5HT1A receptors. According to our previous studies with the Beta-Microprobe (J Nucl Med 2002, 43(2):227-33; Eur J Nucl Med 2002 29(9) 1237-47), the radioactive signals measured with the PIXSIC pixels are reproducible and well-correlated with the distributions of the targeted receptors. The simultaneous measurement of implanted rats in a small animal PET camera confirmed the similarity between PIXSIC and microPET time-activity curves. Moreover, the binding curves highlighted the possibility for PIXSIC to distinguish different tracer kinetics within the structure of interest (cortex/striatum or cortex/hippocampus) in accordance to the stereotaxic location of the pixels. In addition, PIXSIC allowed us to perform the first kinetic measurements of [11C]-raclopride and [18F]-MPPF on awake and freely moving rats. In conclusion, PIXSIC constitutes an unprecedented instrumental methodology for connecting PET molecular imaging and behavioral measurements with freely-moving rodents.
- Published
- 2013
10. Organic cation transporter 2 (OCT2) is implicated in the response to stress
- Author
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Bacq, A., Balasse, L., Courousse, T., Louis, F., Giros, B., Sophie Gautron, Physiopathologie des maladies psychiatriques = Pathophysiology of Psychiatric Disorders (NPS-07), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; no abstract
- Published
- 2012
11. Rôle des AGPIn-3 dans les fonctions cognitives. Modulation par le stress et le vieillissement cérébral
- Author
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Balasse, L., Marie Hennebelle, Alizée Latour, Monique Lavialle, Isabelle Denis, Sylvie Vancassel, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de nutrition et sécurité alimentaire, and Institut National de la Recherche Agronomique (INRA)
- Subjects
[SDV]Life Sciences [q-bio] - Published
- 2011
12. PIXSIC, a Pixelated β+-Sensitive Probe for Radiopharmacological Investigations in Rat Brain: Binding Studies with [18F]MPPF
- Author
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Balasse, L., primary, Maerk, J., additional, Pain, F., additional, Genoux, A., additional, Fieux, S., additional, Morel, C., additional, Gisquet-Verrier, P., additional, Zimmer, L., additional, and Lanièce, P., additional
- Published
- 2014
- Full Text
- View/download PDF
13. Brain organic cation transporter 2 controls response and vulnerability to stress and GSK3β signaling
- Author
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Couroussé, T, primary, Bacq, A, additional, Belzung, C, additional, Guiard, B, additional, Balasse, L, additional, Louis, F, additional, Le Guisquet, A-M, additional, Gardier, A M, additional, Schinkel, A H, additional, Giros, B, additional, and Gautron, S, additional
- Published
- 2014
- Full Text
- View/download PDF
14. A wireless beta-microprobe based on pixelated silicon forin vivobrain studies in freely moving rats
- Author
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Märk, J, primary, Benoit, D, additional, Balasse, L, additional, Benoit, M, additional, Clémens, J C, additional, Fieux, S, additional, Fougeron, D, additional, Graber-Bolis, J, additional, Janvier, B, additional, Jevaud, M, additional, Genoux, A, additional, Gisquet-Verrier, P, additional, Menouni, M, additional, Pain, F, additional, Pinot, L, additional, Tourvielle, C, additional, Zimmer, L, additional, Morel, C, additional, and Laniece, P, additional
- Published
- 2013
- Full Text
- View/download PDF
15. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response
- Author
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Bacq, A, primary, Balasse, L, additional, Biala, G, additional, Guiard, B, additional, Gardier, A M, additional, Schinkel, A, additional, Louis, F, additional, Vialou, V, additional, Martres, M-P, additional, Chevarin, C, additional, Hamon, M, additional, Giros, B, additional, and Gautron, S, additional
- Published
- 2011
- Full Text
- View/download PDF
16. Neurochemical characterization of pathways expressing plasma membrane monoamine transporter in the rat brain
- Author
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Vialou, V., primary, Balasse, L., additional, Dumas, S., additional, Giros, B., additional, and Gautron, S., additional
- Published
- 2007
- Full Text
- View/download PDF
17. PIXSIC, a pixelated β⁺-sensitive probe for radiopharmacological investigations in rat brain: binding studies with [¹⁸F]MPPF.
- Author
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Balasse, L, Maerk, J, Pain, F, Genoux, A, Fieux, S, Morel, C, Gisquet-Verrier, P, Zimmer, L, and Lanièce, P
- Abstract
Purpose: The aim of this work was to demonstrate the pharmacokinetic potential of a wireless pixelated β(+)-sensitive probe (PIXSIC).Procedures: The binding of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), a 5-HT1A serotonin receptor radiopharmaceutical, was measured in anesthetized rats and compared to microPET data. The effects of a 5-HT1A antagonist injection on in vivo [(18)F]MPPF binding were monitored by PIXSIC.Results: PIXSIC allowed differentiating the radioactive kinetics according to the location of its pixels in the hippocampus, cortex, corpus callosum, and cerebellum. The device accurately detected the changes in [(18)F]MPPF binding, after 5-HT1A antagonist blockade. The time-activity curves were reproducible and consistent with kinetics obtained simultaneously with a microPET camera.Conclusions: These results demonstrate the ability of the PIXSIC device to record reliably the binding of PET ligands, with a high spatiotemporal resolution in anesthetized rodents. These first in vivo results are a key stage on the path to its implementation in awake freely moving animals. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
18. PIXSIC, a Pixelated β-Sensitive Probe for Radiopharmacological Investigations in Rat Brain: Binding Studies with [F]MPPF.
- Author
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Balasse, L., Maerk, J., Pain, F., Genoux, A., Fieux, S., Morel, C., Gisquet-Verrier, P., Zimmer, L., and Lanièce, P.
- Subjects
PHARMACOKINETICS ,PIPERAZINE ,SEROTONIN ,RADIOPHARMACEUTICALS ,CORPUS callosum - Abstract
Purpose: The aim of this work was to demonstrate the pharmacokinetic potential of a wireless pixelated β-sensitive probe (PIXSIC). Procedures: The binding of 2′-methoxyphenyl-( N-2′-pyridinyl)-p-[F]fluoro-benzamidoethylpiperazine ([F]MPPF), a 5-HT serotonin receptor radiopharmaceutical, was measured in anesthetized rats and compared to microPET data. The effects of a 5-HT antagonist injection on in vivo [F]MPPF binding were monitored by PIXSIC. Results: PIXSIC allowed differentiating the radioactive kinetics according to the location of its pixels in the hippocampus, cortex, corpus callosum, and cerebellum. The device accurately detected the changes in [F]MPPF binding, after 5-HT antagonist blockade. The time-activity curves were reproducible and consistent with kinetics obtained simultaneously with a microPET camera. Conclusions: These results demonstrate the ability of the PIXSIC device to record reliably the binding of PET ligands, with a high spatiotemporal resolution in anesthetized rodents. These first in vivo results are a key stage on the path to its implementation in awake freely moving animals. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
19. A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats.
- Author
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Märk, J., Benoit, D., Balasse, L., Benoit, M., Clémens, J. C., Fieux, S., Fougeron, D., Graber-Bolis, J., Janvier, B., Jevaud, M., Genoux, A., Gisquet-Verrier, P., Menouni, M., Pain, F., Pinot, L., Tourvielle, C., Zimmer, L., Morel, C., and Laniece, P.
- Subjects
MICROPROBE analysis ,BRAIN imaging ,BEHAVIORAL research ,RADIOACTIVE tracers ,SILICON diodes ,LABORATORY rats - Abstract
The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracerswith additional imaging features in freelymoving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions.Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
20. Pharmacokinetic studies and modeling to efficiently predict nanoradiotracer PET biodistribution
- Author
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Ou, J., Louis, B., Sakiroff, L., Nail, V., Balasse, L., Bouhlel, A., Nachar, O., Moyon, A., Roussel, T., Françoise DIGNAT-GEORGE, Peng, L., Guillet, B., Garrigue, P., Gattacceca, F., and karlsen, melanie
- Subjects
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
21. The Evolving Role of Succinate in Tumor Metabolism
- Author
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Garrigue, P., Bodin-Hullin, A., Moyon, A., Balasse, L., Fernandez, S., Essamet, W., Françoise DIGNAT-GEORGE, Pacak, K., Taieb, D., and Guillet, B.
22. Development of a new 68Ga radiolabelled PET imaging agent to evaluate in vivo expression of angiomotin in malignant brain tumors
- Author
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Moyon, A., Garrigue, P., Brige, P., Nollet, M., Balasse, L., Fernandez, S., Blot-Chabaud, M., Françoise DIGNAT-GEORGE, and Guillet, B.
23. Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.
- Author
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Louis B, Nail V, Nachar O, Bouhlel A, Moyon A, Balasse L, Simoncini S, Chabert A, Fernandez S, Brige P, Hache G, Tintaru A, Morgat C, Dignat-George F, Garrigue P, and Guillet B
- Subjects
- Animals, Mice, Swine, Apelin, Apelin Receptors, Gallium Radioisotopes, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography methods, Molecular Imaging methods, Oligopeptides, Adenocarcinoma, Colonic Neoplasms
- Abstract
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 ([
68 Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [67 Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [68 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 [68 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 [68 Ga]Ga-AP747 and [68 Ga]Ga-RGD2 small animal PET/CT. [68 Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [68 Ga]Ga-RGD2 . Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [68 Ga]Ga-AP747 PET signal was more than twice higher than that of [68 Ga]Ga-RGD2 on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [68 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, [68 Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [68 Ga]Ga-RGD2 ., (© 2023. The Author(s).)- Published
- 2023
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24. In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage.
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Abellan Lopez M, Hutter L, Pagin E, Vélier M, Véran J, Giraudo L, Dumoulin C, Arnaud L, Macagno N, Appay R, Daniel L, Guillet B, Balasse L, Caso H, Casanova D, Bertrand B, Dignat F, Hermant L, Riesterer H, Guillemot F, Sabatier F, and Magalon J
- Abstract
Introduction: An autologous split-thickness skin graft (STSG) is a standard treatment for coverage of full-thickness skin defects. However, this technique has two major drawbacks: the use of general anesthesia for skin harvesting and scar sequelae on the donor site. In order to reduce morbidity associated with STSG harvesting, researchers have developed autologous dermo-epidermal substitutes (DESs) using cell culture, tissue engineering, and, more recently, bioprinting approaches. This study assessed the manufacturing reliability and in vivo efficacy of a large-size good manufacturing practice (GMP)-compatible bio-printed human DES, named Poieskin
® , for acute wound healing treatment. Methods: Two batches (40 cm2 each) of Poieskin® were produced, and their reliability and homogeneity were assessed using histological scoring. Immunosuppressed mice received either samples of Poieskin® ( n = 8) or human STSG ( n = 8) immediately after longitudinal acute full-thickness excision of size 1 × 1.5 cm, applied on the skeletal muscle plane. The engraftment rate was assessed through standardized photographs on day 16 of the follow-up. Moreover, wound contraction, superficial vascularization, and local inflammation were evaluated via standardized photographs, laser Doppler imaging, and PET imaging, respectively. Histological analysis was finally performed after euthanasia. Results: Histological scoring reached 75% ± 8% and 73% ± 12%, respectively, displaying a robust and homogeneous construct. Engraftment was comparable for both groups: 91.8% (SD = 0.1152) for the Poieskin® group versus 100% (SD = 0) for the human STSG group. We did not record differences in either graft perfusion, PET imaging, or histological scoring on day 16. Conclusion: Poieskin® presents consistent bioengineering manufacturing characteristics to treat full-thickness cutaneous defects as an alternative to STSG in clinical applications. Manufacturing of Poieskin® is reliable and homogeneous, leading to a clinically satisfying rate of graft take compared to the reference human STSG in a mouse model. These results encourage the use of Poieskin® in phase I clinical trials as its manufacturing procedure is compatible with pharmaceutical guidelines., Competing Interests: Author FG is the CEO and founder of POIETIS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abellan Lopez, Hutter, Pagin, Vélier, Véran, Giraudo, Dumoulin, Arnaud, Macagno, Appay, Daniel, Guillet, Balasse, Caso, Casanova, Bertrand, Dignat, Hermant, Riesterer, Guillemot, Sabatier and Magalon.)- Published
- 2023
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25. Rapid nanobody-based imaging of mesothelin expressing malignancies compatible with blocking therapeutic antibodies.
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Benloucif A, Meyer D, Balasse L, Goubard A, Danner L, Bouhlel A, Castellano R, Guillet B, Chames P, and Kerfelec B
- Subjects
- Humans, Tissue Distribution, Positron-Emission Tomography, Antibodies, Blocking, Mesothelin, Neoplasms diagnostic imaging, Neoplasms therapy
- Abstract
Introduction: Mesothelin (MSLN) is overexpressed in a wide variety of cancers with few therapeutic options and has recently emerged as an attractive target for cancer therapy, with a large number of approaches currently under preclinical and clinical investigation. In this respect, developing mesothelin specific tracers as molecular companion tools for predicting patient eligibility, monitoring then response to mesothelin-targeting therapies, and tracking the evolution of the disease or for real-time visualisation of tumours during surgery is of growing importance., Methods: We generated by phage display a nanobody (Nb S1) and used enzymatic approaches were used to site-directed conjugate Nb S1 with either ATTO 647N fluorochrome or NODAGA chelator for fluorescence and positron emission tomography imaging (PET) respectively., Results: We demonstrated that Nb S1 displays a high apparent affinity and specificity for human mesothelin and demonstrated that the binding, although located in the membrane distal domain of mesothelin, is not impeded by the presence of MUC16, the only known ligand of mesothelin, nor by the therapeutic antibody amatuximab. In vivo experiments showed that both ATTO 647N and [
68 Ga]Ga-NODAGA-S1 rapidly and specifically accumulated in mesothelin positive tumours compared to mesothelin negative tumours or irrelevant Nb with a high tumour/background ratio. The ex vivo biodistribution profile analysis also confirmed a significantly higher uptake of Nb S1 in MSLN-positive tumours than in MSLNlow tumours., Conclusion: We demonstrated for the first time the use of an anti-MSLN nanobody as PET radiotracer for same day imaging of MSLN+ tumours, targeting an epitope compatible with the monitoring of amatuximab-based therapies and current SS1-derived-drug conjugates., Competing Interests: AbB, DM, PC, and BK are listed as inventors on a pending patent application related to the nanobody described in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Benloucif, Meyer, Balasse, Goubard, Danner, Bouhlel, Castellano, Guillet, Chames and Kerfelec.)- Published
- 2023
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26. Sublingual Atropine Administration as a Tool to Decrease Salivary Glands' PSMA-Ligand Uptake: A Preclinical Proof of Concept Study Using [ 68 Ga]Ga-PSMA-11.
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Nail V, Louis B, Moyon A, Chabert A, Balasse L, Fernandez S, Hache G, Garrigue P, Taïeb D, and Guillet B
- Abstract
Prostate 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.
- Published
- 2022
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27. Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging.
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Giraud R, Moyon A, Simoncini S, Duchez AC, Nail V, Chareyre C, Bouhlel A, Balasse L, Fernandez S, Vallier L, Hache G, Sabatier F, Dignat-George F, Lacroix R, Guillet B, and Garrigue P
- Abstract
Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration., Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia., Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function., Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.
- Published
- 2022
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28. Comparison of a New 68 Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction.
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Moyon A, Garrigue P, Fernandez S, Hubert F, Balasse L, Brige P, Hache G, Nail V, Blot-Chabaud M, Dignat-George F, Rochais F, and Guillet B
- Subjects
- Animals, Disease Models, Animal, Fibrosis metabolism, Fibrosis pathology, Fluorodeoxyglucose F18 metabolism, Integrin alphaVbeta3 metabolism, Male, Mice, Myocardial Infarction pathology, Myocardium metabolism, Myocardium pathology, Neovascularization, Pathologic pathology, Positron-Emission Tomography methods, CD146 Antigen metabolism, Gallium Radioisotopes metabolism, Myocardial Infarction metabolism, Neovascularization, Pathologic metabolism, Oligopeptides metabolism, Radiopharmaceuticals metabolism
- Abstract
Ischemic vascular diseases are associated with elevated tissue expression of angiomotin (AMOT), a promising molecular target for PET imaging. On that basis, we developed an AMOT-targeting radiotracer,
68 Ga-sCD146 and performed the first in vivo evaluation on a myocardial infarction mice model and then, compared AMOT expression and αv β3 -integrin expression with68 Ga-sCD146 and68 Ga-RGD2 imaging. After myocardial infarction (MI) induced by permanent ligation of the left anterior descending coronary artery, myocardial perfusion was evaluated by Doppler ultrasound and by18 F-FDG PET imaging.68 Ga-sCD146 and68 Ga-RGD2 PET imaging were performed. In myocardial infarction model, heart-to-muscle ratio of68 Ga-sCD146 imaging showed a significantly higher radiotracer uptake in the infarcted area of MI animals than in sham (* p = 0.04). Interestingly, we also observed significant correlations between68 Ga-sCD146 imaging and delayed residual perfusion assessed by18 F-FDG (* p = 0.04), with lowest tissue fibrosis assessed by histological staining (* p = 0.04) and with functional recovery assessed by ultrasound imaging (** p = 0.01).68 Ga-sCD146 demonstrated an increase in AMOT expression after MI. Altogether, significant correlations of early post-ischemic68 Ga-sCD146 uptake with late heart perfusion, lower tissue fibrosis and better functional recovery, make68 Ga-sCD146 a promising radiotracer for tissue angiogenesis assessment after MI.- Published
- 2021
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29. Renal SPECT/CT with 99mTc-dimercaptosuccinic acid is a non-invasive predictive marker for the development of interstitial fibrosis in a rat model of renal insufficiency.
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Bobot M, Hache G, Moyon A, Fernandez S, Balasse L, Daniel L, Garrigue P, Brige P, Chopinet S, Dignat-George F, Brunet P, Burtey S, and Guillet B
- Subjects
- Animals, Biomarkers, Fibrosis, Humans, Kidney, Kidney Function Tests, Male, Rats, Renal Insufficiency, Chronic, Tomography, Emission-Computed, Single-Photon methods, Tomography, X-Ray Computed, Technetium Tc 99m Dimercaptosuccinic Acid
- Abstract
Background: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. Renal fibrosis plays a major role in the progression of CKD but, to date, histology remains the gold standard to assess fibrosis. Non-invasive techniques are needed to assess renal parenchymal impairment and to perform the longitudinal evaluation of renal structure. Thus we evaluated renal isotopic imaging by single-photon emission computed tomography/computed tomography (SPECT/CT) with technetium-99m (99mTc)-dimercaptosuccinic acid (DMSA) to monitor renal impairment during renal insufficiency in rats., Methods: Renal insufficiency was induced by an adenine-rich diet (ARD) at 0.25 and 0.5% for 28 days. Renal dysfunction was evaluated by assaying biochemical markers and renal histology. Renal parenchymal impairment was assessed by SPECT/CT isotopic imaging with 99mTc-DMSA on Days 0, 7, 14, 21, 28, 35 and 49., Results: Compared with controls, ARD rats developed renal dysfunction characterized by increased serum creatinine and blood urea nitrogen, fibrosis and tubulointerstitial damage in the kidneys, with a dose-dependent effect of the adenine concentration. 99mTc-DMSA SPECT-CT imaging showed a significant decrease in renal uptake over time in 0.25 and 0.5% ARD rats compared with control rats (P = 0.011 and P = 0.0004, respectively). 99mTc-DMSA uptake on Day 28 was significantly inversely correlated with Sirius red staining evaluated on Day 49 (r = 0.89, P < 0.0001, R2 = 0.67)., Conclusions: 99mTc-DMSA renal scintigraphy allows a longitudinal follow-up of risk of renal fibrosis in rats. We found that the reduction of renal parenchyma in ARD rats is inversely proportional to newly formed fibrous tissue in the kidney. Our results suggest that 99mTc-DMSA renal scintigraphy may be a useful non-invasive prognostic marker of the development of renal fibrosis in animals and should be tested in humans., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2021
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30. Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study.
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Moyon A, Garrigue P, Balasse L, Fernandez S, Brige P, Bouhlel A, Hache G, Dignat-George F, Taïeb D, and Guillet B
- Subjects
- Acute Disease, Animals, Endothelial Cells metabolism, Female, Gallium Radioisotopes, Hindlimb blood supply, Hindlimb diagnostic imaging, Hindlimb physiopathology, Injections, Mice, Muscles drug effects, Muscles metabolism, Peptides, Cyclic chemistry, Perfusion, Positron Emission Tomography Computed Tomography, Receptors, G-Protein-Coupled metabolism, Succinic Acid pharmacology, Ischemia diagnostic imaging, Ischemia physiopathology, Multimodal Imaging, Neovascularization, Physiologic drug effects, Recovery of Function drug effects, Succinic Acid administration & dosage
- Abstract
Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([
68 Ga]Ga-RGD2 ) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.- Published
- 2021
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31. Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis.
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Roseren F, Pithioux M, Robert S, Balasse L, Guillet B, Lamy E, and Roffino S
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- Animals, Disease Models, Animal, Durapatite chemistry, Flow Cytometry, Hematopoietic Stem Cell Mobilization, Kinetics, Male, Mesenchymal Stem Cells cytology, Neovascularization, Physiologic drug effects, Osteoblasts metabolism, Osteoclasts drug effects, Positron-Emission Tomography, Rats, Rats, Sprague-Dawley, Single Photon Emission Computed Tomography Computed Tomography, Stem Cells metabolism, Bone Regeneration drug effects, Granulocyte Colony-Stimulating Factor administration & dosage, Osteogenesis, Distraction, Stem Cells cytology
- Abstract
Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO.
- Published
- 2021
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32. Silicon-Containing Neurotensin Analogues as Radiopharmaceuticals for NTS 1 -Positive Tumors Imaging.
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Fanelli R, Chastel A, Previti S, Hindié E, Vimont D, Zanotti-Fregonara P, Fernandez P, Garrigue P, Lamare F, Schollhammer R, Balasse L, Guillet B, Rémond E, Morgat C, and Cavelier F
- Subjects
- Animals, HT29 Cells, Humans, Mice, Nude, Neoplasms diagnostic imaging, Neurotensin analogs & derivatives, Positron-Emission Tomography methods, Radiopharmaceuticals chemistry, Receptors, Neurotensin analysis, Silicon chemistry
- Abstract
Several independent studies have demonstrated the overexpression of NTS
1 in various malignancies, which make this receptor of interest for imaging and therapy. To date, radiolabeled neurotensin analogues suffer from low plasmatic stability and thus insufficient availability for high uptake in tumors. We report the development of68 Ga-radiolabeled neurotensin analogues with improved radiopharmaceutical properties through the introduction of the silicon-containing amino acid trimethylsilylalanine (TMSAla). Among the series of novel radiolabeled neurotensin analogues, [68 Ga] Ga- JMV6659 exhibits high hydrophilicity (log D7.4 = -3.41 ± 0.14), affinity in the low nanomolar range toward NTS1 ( Kd = 6.29 ± 1.37 nM), good selectivity ( Kd NTS1 / Kd NTS2 = 35.9), and high NTS1 -mediated internalization. It has lower efflux and prolonged plasmatic half-life in human plasma as compared to the reference compound ([68 Ga]Ga-JMV6661 bearing the minimum active fragment of neurotensin and the same linker and chelate as other analogues). In nude mice bearing HT-29 xenograft, [68 Ga]Ga-JMV6659 uptake reached 7.8 ± 0.54 %ID/g 2 h post injection. Uptake was decreased to 1.38 ± 0.71 %ID/g with injection of excess of non-radioactive neurotensin. Radiation dose as extrapolated to human was estimated as 2.35 ± 0.6 mSv for a standard injected activity of 100MBq. [68 Ga]Ga-JMV6659 was identified as a promising lead compound suitable for PET imaging of NTS1 -expressing tumors.- Published
- 2020
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33. Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study.
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Ding L, Lyu Z, Louis B, Tintaru A, Laurini E, Marson D, Zhang M, Shao W, Jiang Y, Bouhlel A, Balasse L, Garrigue P, Mas E, Giorgio S, Iovanna J, Huang Y, Pricl S, Guillet B, and Peng L
- Subjects
- Tissue Distribution, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Dendrimers, Nanoparticles
- Abstract
Bioimaging has revolutionized medicine by providing accurate information for disease diagnosis and treatment. Nanotechnology-based bioimaging is expected to further improve imaging sensitivity and specificity. In this context, supramolecular nanosystems based on self-assembly of amphiphilic dendrimers for single photon emission computed tomography (SPECT) bioimaging are developed. These dendrimers bear multiple In
3+ radionuclides at their terminals as SPECT reporters. By replacing the macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid cage with the smaller 1,4,7-triazacyclononane-1,4,7-triacetic acid scaffold as the In3+ chelator, the corresponding dendrimer exhibits neutral In3+ -complex terminals in place of negatively charged In3+ -complex terminals. This negative-to-neutral surface charge alteration completely reverses the zeta-potential of the nanosystems from negative to positive. As a consequence, the resulting SPECT nanoprobe generates a highly sought-after biodistribution profile accompanied by a drastically reduced uptake in liver, leading to significantly improved tumor imaging. This finding contrasts with current literature reporting that positively charged nanoparticles have preferential accumulation in the liver. As such, this study provides new perspectives for improving the biodistribution of positively charged nanosystems for biomedical applications., (© 2020 Wiley-VCH GmbH.)- Published
- 2020
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34. Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.
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Bobot M, Thomas L, Moyon A, Fernandez S, McKay N, Balasse L, Garrigue P, Brige P, Chopinet S, Poitevin S, Cérini C, Brunet P, Dignat-George F, Burtey S, Guillet B, and Hache G
- Subjects
- Adenine, Animals, Blood-Brain Barrier diagnostic imaging, Blood-Brain Barrier drug effects, Carbon pharmacology, Cognitive Dysfunction etiology, Disease Models, Animal, Indican blood, Indican cerebrospinal fluid, Male, Mice, Knockout, Nephrectomy, Neuropsychological Tests, Oxides pharmacology, Permeability, Radiopharmaceuticals metabolism, Rats, Rats, Sprague-Dawley, Receptors, Aryl Hydrocarbon genetics, Renal Insufficiency, Chronic complications, Single Photon Emission Computed Tomography Computed Tomography, Technetium Tc 99m Pentetate metabolism, Uremia complications, Blood-Brain Barrier metabolism, Cognitive Dysfunction metabolism, Indican pharmacology, Receptors, Aryl Hydrocarbon metabolism, Renal Insufficiency, Chronic physiopathology, Uremia blood
- Abstract
Background: Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells., Methods: To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR
-/- knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of99m Tc-DTPA, an imaging marker of blood-brain barrier permeability., Results: In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between99m Tc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR-/- knockout mice were protected against indoxyl sulfate-induced blood-brain barrier disruption and cognitive impairment., Conclusions: AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD., (Copyright © 2020 by the American Society of Nephrology.)- Published
- 2020
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35. A self-assembling amphiphilic dendrimer nanotracer for SPECT imaging.
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Ding L, Lyu Z, Tintaru A, Laurini E, Marson D, Louis B, Bouhlel A, Balasse L, Fernandez S, Garrigue P, Mas E, Giorgio S, Pricl S, Guillet B, and Peng L
- Subjects
- Adenocarcinoma diagnostic imaging, Animals, Cell Line, Tumor, Chelating Agents chemical synthesis, Chelating Agents chemistry, Dendrimers chemical synthesis, Heterocyclic Compounds, 1-Ring chemical synthesis, Heterocyclic Compounds, 1-Ring chemistry, Humans, Indium, Indium Radioisotopes, Mice, Micelles, Pancreatic Neoplasms diagnostic imaging, Radioisotopes, Surface-Active Agents chemical synthesis, Tomography, Emission-Computed, Single-Photon methods, Dendrimers chemistry, Nanostructures chemistry, Surface-Active Agents chemistry
- Abstract
Bioimaging has revolutionized modern medicine, and nanotechnology can offer further specific and sensitive imaging. We report here an amphiphilic dendrimer able to self-assemble into supramolecular nanomicelles for effective tumor detection using SPECT radioimaging. This highlights the promising potential of supramolecular dendrimer platforms for biomedical imaging.
- Published
- 2019
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36. Tracking Dynamics of Spontaneous Tumors in Mice Using Photon-Counting Computed Tomography.
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Cassol F, Portal L, Richelme S, Dupont M, Boursier Y, Arechederra M, Auphan-Anezin N, Chasson L, Laprie C, Fernandez S, Balasse L, Lamballe F, Dono R, Guillet B, Lawrence T, Morel C, and Maina F
- Abstract
Computed tomography is a powerful medical imaging modality for longitudinal studies in cancer to follow neoplasia progression and evaluate anticancer therapies. Here, we report the generation of a photon-counting micro-computed tomography (PC-CT) method based on hybrid pixel detectors with enhanced sensitivity and precision of tumor imaging. We then applied PC-CT for longitudinal imaging in a clinically relevant liver cancer model, the Alb-R26
Met mice, and found a remarkable heterogeneity in the dynamics for tumors at the initiation phases. Instead, the growth curve of evolving tumors exhibited a comparable exponential growth, with a constant doubling time. Furthermore, longitudinal PC-CT imaging in mice treated with a combination of MEK and BCL-XL inhibitors revealed a drastic tumor regression accompanied by a striking remodeling of macrophages in the tumor microenvironment. Thus, PC-CT is a powerful system to detect cancer initiation and progression, and to monitor its evolution during treatment., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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37. Probing the Cellular Size Distribution in Cell Samples Undergoing Cell Death.
- Author
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Franceschini E, Balasse L, Roffino S, and Guillet B
- Subjects
- Apoptosis physiology, Cell Culture Techniques, Flow Cytometry methods, Humans, In Vitro Techniques, Phantoms, Imaging, Adenocarcinoma pathology, Cell Death physiology, Colonic Neoplasms pathology, Ultrasonography methods
- Abstract
A polydisperse scattering model adapted for concentrated medium, namely the polydisperse structure factor model, was examined to explain the backscatter coefficients (BSCs) measured from packed cell samples undergoing cell death. Cell samples were scanned using high-frequency ultrasound in the 10-42 MHz bandwidth. A parameter estimation procedure was proposed to estimate the volume fraction and the relative impedance contrast that could explain the changes in BSC pattern by considering the actual change in cellular size distribution. Quantitative ultrasound parameters were estimated and related to the percentage of dead cells determined by flow cytometry. The standard deviation of scatterer size distribution extracted from the polydisperse structure factor model and the spectral intercept were found to be strongly correlated to the percentage of dead cells (r
2 = 0.79 and r2 = 0.72, respectively). This study contributes to the understanding of ultrasonic scattering from cells undergoing cell death toward the monitoring of cancer therapy., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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38. Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors.
- Author
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Garrigue P, Tang J, Ding L, Bouhlel A, Tintaru A, Laurini E, Huang Y, Lyu Z, Zhang M, Fernandez S, Balasse L, Lan W, Mas E, Marson D, Weng Y, Liu X, Giorgio S, Iovanna J, Pricl S, Guillet B, and Peng L
- Subjects
- Animals, Cell Line, Tumor, Colonic Neoplasms pathology, Contrast Media chemistry, Contrast Media pharmacokinetics, Coordination Complexes blood, Coordination Complexes chemistry, Dendrimers chemistry, Fluorodeoxyglucose F18 chemistry, Gallium Radioisotopes blood, Gallium Radioisotopes chemistry, Glioblastoma pathology, Heterocyclic Compounds chemistry, Heterocyclic Compounds, 1-Ring, Heterografts, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Pancreatic Neoplasms pathology, Prostatic Neoplasms pathology, Colonic Neoplasms diagnostic imaging, Coordination Complexes pharmacokinetics, Gallium Radioisotopes pharmacokinetics, Glioblastoma diagnostic imaging, Pancreatic Neoplasms diagnostic imaging, Positron-Emission Tomography methods, Prostatic Neoplasms diagnostic imaging
- Abstract
Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([
18 F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [18 F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)- Published
- 2018
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39. Nonlinear ultrasound parameter to monitor cell death in cancer cell samples.
- Author
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Muleki-Seya P, Payan C, Balasse L, Guillermin R, Roffino S, Guillet B, and Franceschini E
- Subjects
- Adenocarcinoma, Algorithms, Apoptosis drug effects, Colonic Neoplasms diagnostic imaging, Colonic Neoplasms drug therapy, Enzyme Inhibitors administration & dosage, Flow Cytometry methods, HT29 Cells pathology, Humans, Monitoring, Physiologic, Nonlinear Dynamics, Staurosporine administration & dosage, Apoptosis physiology, Colonic Neoplasms pathology, HT29 Cells drug effects, Ultrasonography methods
- Abstract
A scaling subtraction method was proposed to analyze the radio frequency data from cancer cell samples exposed to an anti-cancer drug and to estimate a nonlinear parameter. The nonlinear parameter was found to be well correlated (R
2 = 0.62) to the percentage of dead cells in apoptosis and necrosis. The origin of the nonlinearity may be related to a change in contacts between cells, since the nonlinear parameter was well correlated to the average total coordination number of binary packings (R2 ≥ 0.77). These results suggest that the scaling subtraction method may be used to early quantify chemotherapeutic treatment efficiency.- Published
- 2018
- Full Text
- View/download PDF
40. Early prediction of revascularisation by angiomotin-targeting positron emission tomography.
- Author
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Moyon A, Garrigue P, Balasse L, Fernandez S, Brige P, Nollet M, Hache G, Blot-Chabaud M, Dignat-George F, and Guillet B
- Subjects
- Acetates administration & dosage, Angiomotins, Animals, Blotting, Western, CD146 Antigen administration & dosage, Disease Models, Animal, Gallium Radioisotopes administration & dosage, Heterocyclic Compounds, 1-Ring administration & dosage, Immunohistochemistry, Mice, Prognosis, Intercellular Signaling Peptides and Proteins analysis, Ischemia diagnostic imaging, Ischemia pathology, Microfilament Proteins analysis, Molecular Imaging methods, Neovascularization, Physiologic, Positron-Emission Tomography methods
- Abstract
This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions. Methods: Hindlimb ischaemia was induced by ligature and resection of the right femoral artery in mice, and clinical score and limb perfusion were evaluated up to 30 days after surgery. AMOT expression was evaluated by histology and Western blot analysis. NODAGA-conjugates of AMOT ligand, sCD146, were designed, synthesised and radiolabelled with gallium-68.
68 Ga-sCD146 microPET/CT imaging was performed from day 1 to day 30 after ischaemia.68 Ga-sCD146 specificity for AMOT was evaluated by autoradiography. Results: Immunohistochemistry showed a significant endothelial overexpression of AMOT from day 5 up to day 10 in the ischaemic hindlimb.68 Ga-sCD146 PET signal intensity correlated significantly with AMOT immunohistochemistry evaluation.68 Ga-sCD146 PET imaging showed a significant uptake in the ischaemic hindlimb from day 2 to day 15, peaking on day 5 (ipsi/contralateral ratio = 2.4 ± 1.3, P = 0.0005) and significantly decreased after pharmacological blocking (62.57 ± 11% decrease in PET signal P = 0.032). Finally, we observed a significant correlation between day 568 Ga-sCD146 PET signal intensity and clinical recovery (day 28) or hindlimb perfusion recovery (day 30). Conclusions: This work reports for the first time an early and sustained increase in AMOT expression after hindlimb ischaemia in mice. We therefore developed an AMOT-targeting imaging agent,68 Ga-sCD146, and showed its specific uptake up to 21 days after ischaemic hindlimb using microPET imaging. Correlation of early post-ischaemic PET signal with both delayed perfusion recovery and clinical outcome allows us to postulate that68 Ga-sCD146 represents a promising radiotracer for tissue angiogenesis assessment., Competing Interests: Competing Interests: This work was supported by Fondation de l'Avenir, MSD avenir and a patent (B2444PC00) was registered at the European Patent Office. The authors have declared that no competing interest exists.- Published
- 2018
- Full Text
- View/download PDF
41. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.
- Author
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Aidoud N, Delplanque B, Baudry C, Garcia C, Moyon A, Balasse L, Guillet B, Antona C, Darmaun D, Fraser K, Ndiaye S, Leruyet P, and Martin JC
- Subjects
- Animals, Animals, Newborn, Arachidonic Acid metabolism, Brain diagnostic imaging, Fatty Acids metabolism, Humans, Infant, Newborn, Milk, Rats, Brain metabolism, Fatty Acids, Unsaturated metabolism, Infant Formula, Positron-Emission Tomography methods
- Abstract
We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.
- Published
- 2018
- Full Text
- View/download PDF
42. Stem cell properties of peripheral blood endothelial progenitors are stimulated by soluble CD146 via miR-21: potential use in autologous cell therapy.
- Author
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Essaadi A, Nollet M, Moyon A, Stalin J, Simoncini S, Balasse L, Bertaud A, Bachelier R, Leroyer AS, Sarlon G, Guillet B, Dignat-George F, Bardin N, and Blot-Chabaud M
- Subjects
- Adolescent, Adult, Animals, Blotting, Western, Cell Proliferation physiology, Flow Cytometry, Hindlimb pathology, Humans, Ischemia therapy, Male, Mice, Mice, Nude, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells cytology, Stem Cells physiology, Young Adult, CD146 Antigen metabolism, Cell- and Tissue-Based Therapy methods, Endothelial Cells cytology, MicroRNAs metabolism, Stem Cells metabolism
- Abstract
Cell-based therapies constitute a real hope for the treatment of ischaemic diseases. One of the sources of endothelial progenitors for autologous cell therapy is Endothelial Colony Forming Cells (ECFC) that can be isolated from peripheral blood. However, their use is limited by their low number in the bloodstream and the loss of their stem cell phenotype associated with the acquisition of a senescent phenotype in culture. We hypothesized that adding soluble CD146, a novel endothelial growth factor with angiogenic properties, during the isolation and growth procedures could improve their number and therapeutic potential. Soluble CD146 increased the number of isolated peripheral blood ECFC colonies and lowered their onset time. It prevented cellular senescence, induced a partial mesenchymal phenotype and maintained a stem cell phenotype by stimulating the expression of embryonic transcription factors. These different effects were mediated through the induction of mature miR-21. When injected in an animal model of hindlimb ischaemia, sCD146-primed ECFC isolated from 40 ml of blood from patients with peripheral arterial disease were able to generate new blood vessels and restore blood flow. Treatment with sCD146 could thus constitute a promising strategy to improve the use of autologous cells for the treatment of ischaemic diseases.
- Published
- 2018
- Full Text
- View/download PDF
43. The Evolving Role of Succinate in Tumor Metabolism: An 18 F-FDG-Based Study.
- Author
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Garrigue P, Bodin-Hullin A, Balasse L, Fernandez S, Essamet W, Dignat-George F, Pacak K, Guillet B, and Taïeb D
- Subjects
- Animals, Autoradiography, Cell Line, Tumor, Citric Acid Cycle, Connective Tissue metabolism, Fluorodeoxyglucose F18 pharmacokinetics, Fumarates metabolism, Glucose Transporter Type 1 metabolism, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Positron Emission Tomography Computed Tomography, Radiopharmaceuticals pharmacokinetics, Xenograft Model Antitumor Assays, Neoplasms metabolism, Succinates metabolism
- Abstract
In recent years, inherited and acquired mutations in the tricarboxylic acid (TCA) cycle enzymes have been reported in diverse cancers. Pheochromocytomas and paragangliomas often exhibit dysregulation of glucose metabolism, which is also driven by mutations in genes encoding the TCA cycle enzymes or by activation of hypoxia signaling. Pheochromocytomas and paragangliomas associated with succinate dehydrogenase (SDH) deficiency are characterized by high
18 F-FDG avidity. This association is currently only partially explained. Therefore, we hypothesized that accumulation of succinate due to the TCA cycle defect could be the major connecting hub between SDH-mutated tumors and the18 F-FDG uptake profile. Methods: To test whether succinate modifies the18 F-FDG metabolic profile of tumors, we performed in vitro and in vivo (small-animal PET/CT imaging and autoradiography) experiments in the presence of succinate, fumarate, and phosphate-buffered saline (PBS) in different cell models. As a control, we also evaluated the impact of succinate on18 F-fluorocholine uptake and retention. Glucose transporter 1 (GLUT1) immunohistochemistry was performed to assess whether18 F-FDG uptake correlates with GLUT1 staining. Results: Intratumoral injection of succinate significantly increased18 F-FDG uptake at 24 h on small-animal PET/CT imaging and autoradiography. No effect of succinate was observed on cancer cells in vitro, but interestingly, we found that succinate caused increased18 F-FDG uptake by human umbilical vein endothelial cells in a concentration-dependent manner. No significant effect was observed after intratumoral injection of fumarate or PBS. Succinate, fumarate, and PBS have no effect on cell viability, regardless of cell lineage. Intramuscular injection of succinate also significantly increases18 F-FDG uptake by muscle when compared with either PBS or fumarate, highlighting the effect of succinate on connective tissues. No difference was observed between PBS and succinate on18 F-fluorocholine uptake in the tumor and muscle and on hind limb blood flow. GLUT1 expression quantification did not significantly differ between the study groups. Conclusion: The present study shows that succinate stimulates18 F-FDG uptake by endothelial cells, a finding that partially explains the18 F-FDG metabotype observed in tumors with SDH deficiency. Although this study is an18 F-FDG-based approach, it provides an impetus to better characterize the determinants of18 F-FDG uptake in various tumors and their surrounding microenvironment, with a special emphasis on the role of tumor-specific oncometabolites., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
- Full Text
- View/download PDF
44. PIXSIC: A Wireless Intracerebral Radiosensitive Probe in Freely Moving Rats.
- Author
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Balasse L, Maerk J, Pain F, Genoux A, Fieux S, Lefebvre F, Morel C, Gisquet-Verrier P, Lanièce P, and Zimmer L
- Subjects
- Animals, Carbon Radioisotopes, Male, Radionuclide Imaging, Rats, Sprague-Dawley, Brain diagnostic imaging, Movement, Raclopride metabolism, Wireless Technology
- Abstract
The aim of this study was to demonstrate the potential of a wireless pixelated β+-sensitive intracerebral probe (PIXSIC) for in vivo positron emission tomographic (PET) radiopharmacology in awake and freely moving rodents. The binding of [(11)C]raclopride to D2 dopamine receptors was measured in anesthetized and awake rats following injection of the radiotracer. Competitive binding was assessed with a cold raclopride injection 20 minutes later. The device can accurately monitor binding of PET ligands in freely moving rodents with a high spatiotemporal resolution. Reproducible time-activity curves were obtained for pixels throughout the striatum and cerebellum. A significantly lower [(11)C]raclopride tracer-specific binding was observed in awake animals. These first results pave the way for PET tracer pharmacokinetics measurements in freely moving rodents.
- Published
- 2015
45. Influence of omega-3 fatty acid status on the way rats adapt to chronic restraint stress.
- Author
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Hennebelle M, Balasse L, Latour A, Champeil-Potokar G, Denis S, Lavialle M, Gisquet-Verrier P, Denis I, and Vancassel S
- Subjects
- Animals, Behavior, Animal, Body Weight, Chromatography, Gas, Corticosterone blood, Female, Hippocampus metabolism, Rats, Rats, Wistar, Receptors, Glucocorticoid metabolism, Fatty Acids, Omega-3 metabolism, Immobilization, Stress, Physiological
- Abstract
Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.
- Published
- 2012
- Full Text
- View/download PDF
46. An (n-3) polyunsaturated fatty acid-deficient diet disturbs daily locomotor activity, melatonin rhythm, and striatal dopamine in Syrian hamsters.
- Author
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Lavialle M, Champeil-Potokar G, Alessandri JM, Balasse L, Guesnet P, Papillon C, Pévet P, Vancassel S, Vivien-Roels B, and Denis I
- Subjects
- Animals, Corpus Striatum metabolism, Cricetinae, Diet, Dietary Fats, Unsaturated pharmacology, Fatty Acids, Omega-3 administration & dosage, Fatty Acids, Unsaturated metabolism, Female, Male, Mesocricetus, Pineal Gland metabolism, Circadian Rhythm drug effects, Dopamine metabolism, Fatty Acids, Omega-3 pharmacology, Melatonin metabolism, Motor Activity drug effects
- Abstract
Several studies suggest that (n-3) PUFA may play a role in the regulation of cognitive functions, locomotor and exploratory activity, and affective disorders. Additionally, (n-3) PUFA affect pineal function, which is implicated in the sleep-wake rhythm. However, no studies to our knowledge have explored the role of PUFA on the circadian system. We investigated the effect of an (n-3) PUFA-deficient diet on locomotor and pineal melatonin rhythms in Syrian hamsters used as model species in circadian rhythm research. To assess the possible relationship between voluntary wheel running activity and dopaminergic neurotransmission, we also measured endogenous monoamine concentrations in the striatum. Two-month-old male hamsters, fed either an (n-3) PUFA-deficient or an (n-3) PUFA-adequate diet, were housed individually in cages equipped with run wheels. At 3 mo, cerebral structures were extracted for biochemical and cellular analysis. In (n-3) PUFA-deficient hamsters, the induced changes in the pineal PUFA membrane phospholipid composition were associated with a reduction in the nocturnal peak level of melatonin that was 52% lower than in control hamsters (P < 0.001). The (n-3) PUFA-deficient hamsters also had higher diurnal (P < 0.01) and nocturnal (P = 0.001) locomotor activity than the control hamsters, in parallel with activation of striatal dopaminergic function (P < 0.05). The (n-3) PUFA-deficient hamsters exhibited several symptoms: chronic locomotor hyperactivity, disturbance in melatonin rhythm, and striatal hyperdopaminergia. We suggest that an (n-3) PUFA-deficient diet lessens the melatonin rhythm, weakens endogenous functioning of the circadian clock, and plays a role in nocturnal sleep disturbances as described in attention deficit/hyperactivity disorder.
- Published
- 2008
- Full Text
- View/download PDF
47. Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice.
- Author
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Vialou V, Balasse L, Callebert J, Launay JM, Giros B, and Gautron S
- Subjects
- Animals, Brain physiology, Homeostasis genetics, Homeostasis physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Motor Activity physiology, Organic Cation Transport Proteins genetics, Synaptic Transmission physiology, Biogenic Monoamines physiology, Brain metabolism, Organic Cation Transport Proteins deficiency, Organic Cation Transport Proteins physiology, Synaptic Transmission genetics
- Abstract
Organic cation transporters (OCTs) are carrier-type polyspecific permeases known to participate in low-affinity extraneuronal catecholamine uptake in peripheral tissues. OCT3 is the OCT subtype most represented in the brain, yet its implication in central aminergic neurotransmission in vivo had not been directly demonstrated. In a detailed immunohistochemistry study, we show that OCT3 is expressed in aminergic pathways in the mouse brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus and cortex. Although OCT3 was found mainly in neurons, it was also occasionally detected in astrocytes in the SNr, hippocampus and several hypothalamic nuclei. In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. The behavioral characterization of these mutants reveal subtle behavioral alterations such as increased sensitivity to psychostimulants and increased levels of anxiety and stress. Altogether our data support a role of OCT3 in the homeostatic regulation of aminergic neurotransmission in the brain.
- Published
- 2008
- Full Text
- View/download PDF
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