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Your search keyword '"MESH: Heterocyclic Compounds"' showing total 17 results
Start Over Descriptor "MESH: Heterocyclic Compounds" Topic 0302 clinical medicine
17 results on '"MESH: Heterocyclic Compounds"'

1. Modalités de mobilisation des cellules souches hématopoïétiques autologues et objectifs cellulaires en cellules CD34 + : recommandations de la Société francophone de greffe de mœlle et de thérapie cellulaire (SFGM-TC)

Author

Fati Hamzy, Laure Vincent, Anne Brignier, Christine Giraud, Thi Ngoc Phuong Huynh, Francisca Nacimento, Aurélie Levavasseur, Virginie Ader, John De Vos, Katia Bellegarde, Marie-Agnès Guerout-Verite, Yves Rousseau, Ibrahim Yakoub-Agha, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Etablissement français du sang [Rennes] (EFS Bretagne), Université Internationale Abulcasis des Sciences de la Santé (UIASS), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Unité de Recherches sur la Génétique des Protéines Humaines [Bois-Guillaume] (U78 INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CCSD, Accord Elsevier

Subjects
Cancer Research, medicine.medical_specialty, MESH: Heterocyclic Compounds, Bone marrow transplantation, medicine.medical_treatment, Autogreffe de cellules souches, Mobilization, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Autologous stem cell transplantation, 030204 cardiovascular system & hematology, MESH: Cell Separation, Cellules souches hématopoïétiques, MESH: Hematopoietic Stem Cell Mobilization, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Risk Factors, Cell dose, medicine, Autologous transplantation, Radiology, Nuclear Medicine and imaging, MESH: Hematopoietic Cell Growth Factors, MESH: Hematopoietic Stem Cell Transplantation, Mobilisation, Gynecology, MESH: Humans, MESH: Cell Count, business.industry, Plerixafor, MESH: Antigens, CD34, Hematology, General Medicine, MESH: Transplantation, Autologous, MESH: Blood Component Removal, Oncology, MESH: Practice Patterns, Physicians', MESH: Antineoplastic Agents, MESH: Bone Marrow, MESH: Granulocyte Colony-Stimulating Factor, Stem cell, business, Hematopoietic stem cells, 030215 immunology, medicine.drug
Abstract

The modalities of mobilization of hematopoietic stem cells in autologous transplantation have evolved in recent years. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 9th hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2018 in Lille, France, to conduct a review of current practices of the society centers and of international recommendations. The cell dose objectives have been revised. The modalities of mobilization including the use of plerixafor have been specified allowing reaching the objectives of collection while limiting the number of apheresis. Collections failures have become exceptional., Les modalités de mobilisation des cellules souches hématopoïétiques dans le cadre de la greffe autologue ont évolué ces dernières années. Dans le cadre des neuvièmes Ateliers d’harmonisation des pratiques en greffe de cellules souches hématopoïétiques de la Société Francophone de Greffe de Mœlle et de Thérapie Cellulaire (SFGM-TC) qui ont eu lieu à Lille en septembre 2018, un groupe de travail s’est réuni dans le but de réaliser un état des lieux des pratiques des centres de la société et des recommandations internationales. Les objectifs de richesse des greffons ont été revus à la hausse. Les modalités de mobilisation, y compris d’utilisation du plerixafor, ont été précisées, dans l’objectif d’atteindre les objectifs de recueil tout en limitant le nombre de cytaphérèses. Les échecs de recueils sont devenus exceptionnels.

Published
2020

2. Differential activity and selectivity of N‐terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors

Author

Carmen Gallego, Françoise Bachelerie, Françoise Baleux, Erika Cecon, Agnieszka Jaracz-Ros, Pasquale Cutolo, Angélique Levoye, Irina Kufareva, Guillaume Bernadat, Martin Gustavsson, Tracy M. Handel, Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie des Biomolécules - Chemistry of Biomolecules, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Sorbonne Paris Nord, This work was supported by grants from Ensemble Contre le SIDA (SIDACTION), the Institut National de la Santé et de la Recherche Médicale (INSERM), GIS-Network for Rare Diseases and the Agence Nationale de Recherches sur le SIDA (ANRS). We thank members of the Dr. F. Arenzana-Seisdedos laboratory (Laboratoire de Pathogénie Virale, Institut Pasteur, Paris, France) and Dr. R. Jockers (Institut Cochin, Paris, France), who provided critical discussion. We also thank E. Trinquet, N. Gregor and F. Maurin (CisBio International, Marcoule, France) for technical support in HTRF assays. AL was supported by Roux postdoctoral fellowship from Pasteur Institute. I.K. and T.M.H. are supported by NIH R01 grants AI118985 and GM117424. C.G. was beneficiary of a fellowship from Marie Skłodowska-Curie Innovative Training Networks (ITN-ETN) 'ONCOgenic Receptor Network of Excellence and Training' (MSCA-ITN-2014-ETN) and from Fondation pour la Recherche Médicale (FDT201805005700). A.J-R., P.C., C.G., and F. Bachelerie are members of the LabEx LERMIT supported by ANR grant (ANR-10-LABX-33) under the program 'Investissements d'Avenir' (ANR-11-IDEX-0003-01)., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), European Project: 641833,H2020,H2020-MSCA-ITN-2014,ONCORNET(2015), University of California (UC)-University of California (UC), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Baleux, Françoise, Idex Paris-Saclay - - IPS2011 - ANR-11-IDEX-0003 - IDEX - VALID, Research Laboratory on Drugs and Therapeutic Innovation - - LERMIT2010 - ANR-10-LABX-0033 - LABX - VALID, and ONCOgenic Receptor Network of Excellence and Training - ONCORNET - - H20202015-01-01 - 2018-12-31 - 641833 - VALID

Subjects
0301 basic medicine, Protein Conformation, alpha-Helical, ACKR3, Chemokine, Benzylamines, Protein Conformation, [SDV]Life Sciences [q-bio], Gene Expression, pluridimensional efficacy Receptors, MESH: Amino Acid Sequence, Cyclams, CXCR4, MESH: Recombinant Proteins, Chemokine receptor, 0302 clinical medicine, Heterocyclic Compounds, GPCR signaling, Receptors, Cyclic AMP, 2.1 Biological and endogenous factors, Immunology and Allergy, MESH: Molecular Dynamics Simulation, Aetiology, CXCR, Receptor, beta-Arrestins, MESH: Cyclic AMP, biology, MESH: Receptors, CXCR, CXCL12, Recombinant Proteins, Cell biology, [SDV] Life Sciences [q-bio], pluridimensional efficacy, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, embryonic structures, MESH: Oligopeptides, MESH: Protein Conformation, beta-Strand, biological phenomena, cell phenomena, and immunity, MESH: Chemokine CXCL12, Selectivity, chemokine variants, MESH: Chemokine CXCL11, Oligopeptides, Biotechnology, Protein Binding, Agonist, Receptors, CXCR4, MESH: Mutation, MESH: Gene Expression, MESH: Heterocyclic Compounds, medicine.drug_class, Signal Transduction and Genes, 1.1 Normal biological development and functioning, Immunology, Molecular Dynamics Simulation, Article, MESH: Receptors, CXCR4, GPCR Signaling, Vaccine Related, 03 medical and health sciences, MESH: beta-Arrestins, Underpinning research, Biodefense, medicine, Humans, MESH: Protein Binding, Protein Interaction Domains and Motifs, Amino Acid Sequence, Receptors, CXCR, MESH: Protein Conformation, alpha-Helical, MESH: Protein Interaction Domains and Motifs, Binding Sites, MESH: Humans, Prevention, alpha-Helical, Cell Biology, biological factors, Chemokine CXCL12, Chemokine CXCL11, Emerging Infectious Diseases, 030104 developmental biology, HEK293 Cells, MESH: Binding Sites, Mutation, biology.protein, beta-Strand, Protein Conformation, beta-Strand, Biochemistry and Cell Biology
Abstract

Chemokines play critical roles in numerous physiologic and pathologic processes through their action on seven-transmembrane (TM) receptors. The N-terminal domain of chemokines, which is a key determinant of signaling via its binding within a pocket formed by receptors’ TM helices, can be the target of proteolytic processing. An illustrative case of this regulatory mechanism is the natural processing of CXCL12 that generates chemokine variants lacking the first two N-terminal residues. Whereas such truncated variants behave as antagonists of CXCR4, the canonical G protein-coupled receptor of CXCL12, they are agonists of the atypical chemokine receptor 3 (ACKR3/CXCR7), suggesting the implication of different structural determinants in the complexes formed between CXCL12 and its two receptors. Recent analyses have suggested that the CXCL12 N-terminus first engages the TM helices of ACKR3 followed by the receptor N-terminus wrapping around the chemokine core. Here we investigated the first stage of ACKR3-CXCL12 interactions by comparing the activity of substituted or N-terminally truncated variants of CXCL12 toward CXCR4 and ACKR3. We showed that modification of the first two N-terminal residues of the chemokine (K1R or P2G) does not alter the ability of CXCL12 to activate ACKR3. Our results also identified the K1R variant as a G protein-biased agonist of CXCR4. Comparative molecular dynamics simulations of the complexes formed by ACKR3 either with CXCL12 or with the P2G variant identified interactions between the N-terminal 2–4 residues of CXCL12 and a pocket formed by receptor's TM helices 2, 6, and 7 as critical determinants for ACKR3 activation.

Published
2020

3. Impact of gadolinium-based contrast agents on the growth of fish cells lines

Author

Justine Flayac, Marc Parant, E. Perrat, Carole Cossu-Leguille, Bénédicte Sohm, Christophe Rosin, F. Chuburu, C. Cadiou, Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de Reims - UMR 7312 (ICMR), SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), ANR-10-LABX-0021/10-LABX-0021,RESSOURCES21,Strategic metal resources of the 21st century(2010), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'hydrologie de Nancy (LHN), and ANR-10-LABX-0021,RESSOURCES21,Strategic metal resources of the 21st century(2010)

Subjects
Gadolinium DTPA, MESH: Heterocyclic Compounds, Cell Survival, Health, Toxicology and Mutagenesis, Gadolinium, ZF4 cell line, Contrast Media, chemistry.chemical_element, 010501 environmental sciences, 01 natural sciences, Cell Line, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, Cell growth, Meglumine, 0302 clinical medicine, Heterocyclic Compounds, MESH: Contrast Media, Organometallic Compounds, Animals, DOTA, Chelation, Zebrafish, Chelating Agents, 0105 earth and related environmental sciences, Doratem®, Diminution, Chemistry, Cell Cycle, Public Health, Environmental and Occupational Health, MESH: Organometallic Compounds, General Medicine, Magnetic Resonance Imaging, Pollution, MESH: Water Pollutants, Chemical, Contrast agent, Cell culture, Gadoteric acid, Oncorhynchus mykiss, Toxicity, Biophysics, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, Biomarkers, Water Pollutants, Chemical
Abstract

International audience; The present study was the first approach conducted under environmental concentrations of Gd-DOTA and Gd-DTPA-BMA to assess cellular impacts of these compounds. Gd-DOTA (Gadoteric acid) is one of the most stable contrast agent, currently used as Dotarem® formulation during Magnetic Resonance Imaging exams. The study was mainly performed on a Zebra Fish cell line (ZF4; ATCC CRL-2050). At the concentrations of 0.127 nM and 63.59 nM (respectively 20 ng and 10 μg of Gd/L), we did not observed any toxicity of Dotarem® but a slowdown of the cell growth was clearly measured. The effect is independent of medium renewing during 6 days of cell culturing. The same effect was observed i-with Gd-DOTA on another fish cell line (RT W1 gills; ATCC CRL-2523) and ii-with another contrast agent (Gd-DTPA-BMA - Omniscan®) on ZF4 cells. On the ZF4 cell line, the diminution of the cell growth was of the same order during 20 days of exposure to a culture medium spiked with 63.59 nM of Dotarem® and was reversible within the following 8 days when Dotarem® was removed from the medium. As shown by using modified DOTA structure (Zn-DOTA), the effect may be due to the chelating structure of the contrast agent rather than to the Gd ion. Until now, the main attention concerning the impact of Gd-CA on living cells concerned the hazard due to Gd release. According to our results, quantifying the presence of Gd-CA chelating structures in aquatic environments must be also monitored.

Published
2019

4. Evaluation of the antiprion activity of 6-aminophenanthridines and related heterocycles

Author

Justine Evrard, Flavie Soubigou, Cécile Voisset, Nathalie Desban, Pascale Lemoine, Nassima Oumata, Marc Blondel, Serge Bouaziz, Phuhai Nguyen, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), ManRos Therapeutics, Systèmes d'Elevage, Nutrition Animale et Humaine (SENAH), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure Agronomique de Rennes, Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), INSERM Unit 1018, Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Bouaziz, Serge, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, MESH: Heterocyclic Compounds, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Prions, MESH: Mice, Transgenic, MESH: Molecular Structure, Cell, Mice, Transgenic, Saccharomyces cerevisiae, Mice, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, MESH: Prions, MESH: Structure-Activity Relationship, 0302 clinical medicine, Heterocyclic Compounds, Mammalian cell, Drug Discovery, medicine, Animals, MESH: Animals, MESH: Mice, IC50, Phenanthridine, 030304 developmental biology, Pharmacology, 0303 health sciences, Molecular Structure, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Neurodegenerative diseases, Organic Chemistry, Aromaticity, General Medicine, MESH: Phenanthridines, MESH: Saccharomyces cerevisiae, Yeast, Phenanthridines, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], medicine.anatomical_structure, chemistry, Biochemistry, Protein folding, MESH: Models, Molecular, 030217 neurology & neurosurgery, Ex vivo, Protein misfolding
Abstract

International audience; Series of 6-aminophenanthridines and related heterocyclic compounds such as benzonaphtyridines were prepared. Reduction of one of the three aromatic rings was also performed. The compounds were first tested for their antiprion activity in a previously described yeast-based colourimetric prion assay. The most potent derivatives were then assayed ex vivo against the mammalian prion PrP(Sc) in a cell-based assay. Several of the new compounds were found more potent than the parent lead 6-aminophenanthridine. The most promising compounds against yeast and mammalian prions were 8-azido-6-aminophenanthridine (3m), and 7,10-dihydrophenanthridin-6-amine (14). In the mammalian cell-based assay, the IC50 of these two compounds were around 5 μM and 1.8 μM, respectively.

Published
2014

5. A New Magnetic Resonance Imaging Method for Mapping the Cerebral Blood Volume Fraction: The Rapid Steady-State T1 Method

Author

Adriana T. Perles-Barbacaru, Hana Lahrech, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association pour la Recherche sur le Cancer (ARC), and Issartel, Jean-Paul

Subjects
Male, Contrast Media, Blood volume, MESH: Rats, Sprague-Dawley, cerebral blood volume fraction, MESH: Magnetic Resonance Imaging, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, Paramagnetism, 0302 clinical medicine, Nuclear magnetic resonance, Heterocyclic Compounds, Image Processing, Computer-Assisted, magnetic resonance imaging, MESH: Animals, MESH: Models, Theoretical, medicine.diagnostic_test, Brain, MESH: Cerebrovascular Circulation, MESH: Image Processing, Computer-Assisted, Neurology, Cerebrovascular Circulation, intravascular paramagnetic contrast agent, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Cardiology and Cardiovascular Medicine, Hypercapnia, Steady state (electronics), Materials science, MESH: Rats, MESH: Heterocyclic Compounds, longitudinal relaxation time, MESH: Brain, 03 medical and health sciences, Magnetization, Slice preparation, In vivo, rat brain, MESH: Contrast Media, Organometallic Compounds, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, hypercapnia, MESH: Organometallic Compounds, Magnetic resonance imaging, Models, Theoretical, MESH: Male, Rats, Neurology (clinical), Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract

This paper describes a new rapid steady-state T1 (RSS T1) method for mapping the cerebral blood volume fraction ( CBVf) by magnetic resonance imaging (MRI). The principle is based on a two-compartment model of the brain (intra- and extravascular), and the effects of paramagnetic contrast agents on the intravascular longitudinal relaxation time T1. Using appropriate parameters, an Inversion-Recovery-Fast-Low-Angle-Shot sequence acts like a low pass T1 filter, suppressing signals from tissues with T1≫ TR ( TR=repetition time). It was shown in vivo that, exceeding a particular contrast agent dose, the signal reaches its maximum (corresponding to the intravascular equilibrium magnetization), and is maintained for a duration related to the dose. Acquisitions during this steady state divided by an additional measure of the overall (intra- and extravascular) magnetization at thermal equilibrium provides the CBVf. Experiments were performed on healthy rats at 2.35 T using P760 (Gd3+—compound from Guerbet Laboratories) and Gd-DOTA. Because of its high longitudinal relaxivity, P760 is more convenient, and was used to show the feasibility of the method. The CBVf in different structures of the rat brain was compared. The average CBVf for the whole brain slice is 3.29%±0.69% ( n=15). The influence of transendothelial water exchange was quantified and transversal relaxation effects were found negligible in microvasculature. Finally, the sensitivity of the method to CBVf increases under hypercapnia was evaluated (1%/mm Hg PaCO2), demonstrating its potential for longitudinal studies and functional MRI. Clinical applications are feasible since equivalent results were obtained with Gd-DOTA.

Published
2006

6. Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury

Author

Bhaskar Saha, Mohamed Jaber, Kerren Murray, Sophie Péron, Afsaneh Gaillard, Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), BALLION, Bérangère, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Signal Transduction, Benzylamines, Rostral migratory stream, animal diseases, [SDV]Life Sciences [q-bio], MESH: Neurons, Cyclams, Mice, 0302 clinical medicine, Cell Movement, Heterocyclic Compounds, Cortex (anatomy), MESH: Animals, MESH: Anti-HIV Agents, MESH: Cell Movement, Cerebral Cortex, Neurons, Medicine(all), 0303 health sciences, Stem Cells, Neurogenesis, General Medicine, Anatomy, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, MESH: Neuroglia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, MESH: Chemokine CXCL12, Neuroglia, MESH: Neovascularization, Physiologic, Motor cortex, Signal Transduction, Receptors, CXCR4, MESH: Heterocyclic Compounds, Anti-HIV Agents, Subventricular zone, Neovascularization, Physiologic, MESH: Stem Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Receptors, CXCR4, Lesion, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Cell Proliferation, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Progenitor cell, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, Cell Proliferation, Cell Biology, Chemokine CXCL12, MESH: Cerebral Cortex, MESH: Male, Olfactory bulb, MESH: Neurogenesis, Mice, Inbred C57BL, MESH: Astrocytes, nervous system, Astrocytes, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract

International audience; The subventricular zone (SVZ) is the principal neurogenic niche present in the adult non-human mammalian brain. Neurons generated in the SVZ migrate along the rostral migratory stream to reach the olfactory bulb. Brain injuries stimulate SVZ neurogenesis and direct migration of new progenitors to the sites of injury. To date, cortical injury-induced adult SVZ neurogenesis in mice remains ambiguous and migration of neural progenitors to the site of injury has not been studied in detail. Here we report that aspiration lesion in the motor cortex induces a transient, but significant increase in the proliferation as well as neurogenesis in the SVZ. New neural progenitors migrate ectopically to the injured area with the assistance of blood vessels and reactive astrocytes. The SVZ origin of these progenitors was further confirmed using lentiviral transduction. In addition, we show that astrocyte-assisted ectopic migration is regulated by CXCR4/SDF-1 signaling pathway. Finally, upon reaching the lesion area, these progenitors differentiate mainly into glial cells and, to a lesser extent, mature neurons. These data provide a detailed account of the changes occurring in the SVZ and the cortex following lesion, and indicate the potential of the endogenous neural progenitors in cortical repair.

Published
2013

7. How stereological analysis of vascular morphology can quantify the blood volume fraction as a marker for tumor vasculature: comparison with magnetic resonance imaging.: Blood volume quantification by stereology and MRI

Author

Adriana T. Perles-Barbacaru, Régine Farion, Hana Lahrech, Boudewijn van der Sanden, Inserm U836, équipe 7, Nanomédecine et cerveau, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and The study was funded by PhD and post doc stipends from the French Cancer Research Association (ARC, Association pour la Recherche sur le Cancer) and the French National Cancer Institute(INCa, Institut National du Cancer).

Subjects
Models, Anatomic, Pathology, MESH: Blood Volume, Angiogenesis, Gadolinium, Contrast Media, Stereology, MESH: Microscopy, Fluorescence, MESH: Models, Anatomic, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, MESH: Glioma, 0302 clinical medicine, Heterocyclic Compounds, Image Processing, Computer-Assisted, Medicine, MESH: Animals, MESH: Brain Mapping, Brain Mapping, Blood Volume, Blood Volume Determination, Neovascularization, Pathologic, medicine.diagnostic_test, Brain Neoplasms, Glioma, Magnetic Resonance Imaging, MESH: Image Processing, Computer-Assisted, vascular volume fraction, MESH: Microvessels, Neurology, Blood Volume Fraction, MESH: Brain Neoplasms, Original Article, RSST1-MRI, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, MESH: Cell Line, Tumor, MESH: Rats, MESH: Heterocyclic Compounds, MESH: Blood Volume Determination, chemistry.chemical_element, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Tumor vasculature, 03 medical and health sciences, vessel diameter, Cell Line, Tumor, MESH: Contrast Media, Organometallic Compounds, Animals, Rats, Wistar, business.industry, Magnetic resonance imaging, MESH: Organometallic Compounds, MESH: Rats, Wistar, Rats, Microscopy, Fluorescence, Vascular morphology, chemistry, blood volume fraction, Microvessels, stereology, Neurology (clinical), business, MESH: Neovascularization, Pathologic, Neoplasm Transplantation, 030217 neurology & neurosurgery, MESH: Neoplasm Transplantation, GADOTERATE MEGLUMINE
Abstract

To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid-steady-state- T1 (RSST1) magnetic resonance imaging (MRI) method was used for microvascular blood volume fraction (BVf) quantification with a novel contrast agent gadolinium per (3,6 anhydro) α-cyclodextrin (Gd-ACX). In brain tissue contralateral to the tumor, equal BVfs were obtained with Gd-ACX and the clinically approved gadoterate meglumine (Gd-DOTA). Contrary to Gd-DOTA, which leaks out of the tumor vasculature, Gd-ACX was shown to remain vascular in the tumor tissue allowing quantification of the tumor BVf. We sought to confirm the obtained tumor BVf using an independent method: instead of using a ‘standard’ two-dimensional histologic method, we study here how vascular morphometry combined with a stereological technique can be used for three-dimensional assessment of the vascular volume fraction ( VV). The VV is calculated from the vascular diameter and length density. First, the technique is evaluated on simulated data and the healthy rat brain vasculature and is then applied to the same C6 tumor vasculature previously quantified by RSST1-MRI with Gd-ACX. The mean perfused VV and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI.

Published
2012

8. Intracranial solitary fibrous tumor: imaging findings

Author

Jacques Chiras, Fabrice Bonneville, Frédéric Clarençon, Audrey Rousseau, Philippe Cornu, Damien Galanaud, Michèle Kujas, Olivier Naggara, Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neuroradiologie, CHU Toulouse [Toulouse], Service de neuro-pathologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Service de neuroradiologie [Paris], Hôpital Sainte-Anne, Service de Neurochirurgie [CHU Pitié-Salpêtrière], Equipe de Recherche Médicale Appliquée (ERMA), Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
In vivo magnetic resonance spectroscopy, Male, Solitary fibrous tumor, Magnetic Resonance Spectroscopy, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, MESH: Inositol, Contrast Media, Perfusion scanning, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Choline, Diffusion, 0302 clinical medicine, Meninges, Heterocyclic Compounds, MESH: Neuroimaging, MESH: Middle Aged, medicine.diagnostic_test, Brain Neoplasms, MR spectroscopy, MESH: Choline, General Medicine, Middle Aged, Perfusion imaging, Magnetic Resonance Imaging, Solitary Fibrous Tumors, MESH: Brain Neoplasms, Female, Radiology, Tomography, MESH: Tomography, X-Ray Computed, MRI, Adult, medicine.medical_specialty, MESH: Heterocyclic Compounds, chemistry.chemical_element, Neuroimaging, MESH: Diffusion Magnetic Resonance Imaging, 03 medical and health sciences, MESH: Contrast Media, medicine, Organometallic Compounds, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Effective diffusion coefficient, Humans, Radiology, Nuclear Medicine and imaging, Retrospective Studies, MESH: Humans, business.industry, MESH: Magnetic Resonance Spectroscopy, Magnetic resonance imaging, MESH: Adult, MESH: Organometallic Compounds, MESH: Retrospective Studies, MESH: Solitary Fibrous Tumors, medicine.disease, MESH: Male, Diffusion Magnetic Resonance Imaging, chemistry, business, Tomography, X-Ray Computed, MESH: Female, 030217 neurology & neurosurgery, Inositol
Abstract

ERMA; International audience; OBJECTIVE: To study the neuroimaging features of intracranial solitary fibrous tumors (ISFTs). MATERIALS AND METHODS: Retrospective study of neuroimaging features of 9 consecutive histopathologically proven ISFT cases. Location, size, shape, density, signal intensity and gadolinium uptake were studied at CT and MRI. Data collected from diffusion-weighted imaging (DWI) (3 patients), perfusion imaging and MR spectroscopy (2 patients), and DSA (4 patients) were also analyzed. RESULTS: The tumors most frequently arose from the intracranial meninges (7/9), while the other lesions were intraventricular. Tumor size ranged from 2.5 to 10 cm (mean=6.6 cm). They presented multilobular shape in 6/9 patients. Most ISFTs were heterogeneous (7/9) with areas of low T2 signal intensity that strongly enhanced after gadolinium administration (6/8). Erosion of the skull was present in about half of the cases (4/9). Components with decreased apparent diffusion coefficient were seen in 2/3 ISFTs on DWI. Spectroscopy revealed elevated peaks of choline and myo-inositol. MR perfusion showed features of hyperperfusion. CONCLUSION: ISFT should be considered in cases of extra-axial, supratentorial, heterogeneous, hypervascular tumor. Areas of low T2 signal intensity that strongly enhance after gadolinium injection are suggestive of this diagnosis. Restricted diffusion and elevated peak of myo-inositol may be additional valuable features.

Published
2011

9. Synthesis and Structure-Activity Relationships of Constrained Heterocyclic Analogues of Combretastatin A4

Author

Lionel Quentin, Luc Morin-Allory, Renée Pontikis, Jean-Claude Florent, Stéphane Bourg, Johanne Seguin, Guy G. Chabot, Martin Arthuis, Institut Curie [Paris], Conception, synthèse et vectorisation de biomolécules. (CSVB), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris], Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-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)-Université d'Orléans (UO)-Institut de Chimie du CNRS (INC), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Curie, Institut Curie-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-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 Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Conception, synthèse et vectorisation de biomolécules. ( CSVB ), INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Chimie Organique et Analytique ( ICOA ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université d'Orléans ( UO ), Compartimentation et dynamique cellulaires ( CDC ), and Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC )

Subjects
Angiogenesis Inhibitors, MESH: Tubulin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH : Palladium, 01 natural sciences, Biochemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Structure-Activity Relationship, Heterocyclic Compounds, Tubulin, MESH: Stilbenes, MESH : Structure-Activity Relationship, Stilbenes, Drug Discovery, MESH : Catalysis, Moiety, MESH: Animals, MESH: Endothelial Cells, General Pharmacology, Toxicology and Pharmaceutics, ComputingMilieux_MISCELLANEOUS, MESH: Angiogenesis Inhibitors, chemistry.chemical_classification, Biological activity, MESH : Tubulin, MESH : Antineoplastic Agents, 030220 oncology & carcinogenesis, Lactam, Molecular Medicine, MESH: Palladium, Palladium, Lactone, MESH: Cell Line, Tumor, MESH: Heterocyclic Compounds, Stereochemistry, Antineoplastic Agents, Ring (chemistry), Catalysis, MESH : Stilbenes, Structure-Activity Relationship, 03 medical and health sciences, Cell Line, Tumor, MESH : Mice, MESH : Angiogenesis Inhibitors, Animals, Humans, Structure–activity relationship, Oxindole, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Pharmacology, Combretastatin, MESH: Humans, MESH : Cell Line, Tumor, MESH : Endothelial Cells, 010405 organic chemistry, MESH : Humans, Organic Chemistry, Endothelial Cells, MESH: Catalysis, 0104 chemical sciences, MESH : Heterocyclic Compounds, chemistry, MESH: Antineoplastic Agents, MESH : Animals
Abstract

International audience; A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling reaction. The vascular-disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B-ring-constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six-membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular-disrupting agent.

Published
2011

10. Monitoring blood-brain barrier status in a rat model of glioma receiving therapy: dual injection of low-molecular-weight and macromolecular MR contrast media

Author

Cécile Maisin, Audrey Bouchet, Nicolas Coquery, Géraldine Le Duc, Emmanuel L. Barbier, Benjamin Lemasson, Raphaël Serduc, Irène Troprès, Chantal Rémy, Philippe Robert, INSERM U836, équipe 5, Neuro-imagerie fonctionnelle et métabolique, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Oncodesign [Dijon], European Synchrotron Radiation Facility (ESRF), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Guerbet, and Dojat, Michel

Subjects
Male, Pathology, Pyridines, medicine.medical_treatment, MESH: Random Allocation, Contrast Media, MESH: Benzenesulfonates, MESH: Magnetic Resonance Imaging, Neovascularization, MESH: Blood-Brain Barrier, MESH: Glioma, Random Allocation, 0302 clinical medicine, Heterocyclic Compounds, hemic and lymphatic diseases, Medicine, MESH: Animals, Neovascularization, Pathologic, Brain Neoplasms, Benzenesulfonates, Glioma, Sorafenib, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, Blood-Brain Barrier, 030220 oncology & carcinogenesis, Area Under Curve, MESH: Brain Neoplasms, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Niacinamide, medicine.medical_specialty, MESH: Rats, MESH: Heterocyclic Compounds, Macromolecular Substances, Central nervous system, Blood–brain barrier, 03 medical and health sciences, MESH: Analysis of Variance, MESH: Contrast Media, Organometallic Compounds, Animals, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Analysis of Variance, business.industry, Phenylurea Compounds, MESH: Pyridines, MESH: Organometallic Compounds, MESH: Macromolecular Substances, medicine.disease, MESH: Male, Rats, Radiation therapy, Contrast medium, Disease Models, Animal, Permeability (electromagnetism), MESH: Area Under Curve, MESH: Disease Models, Animal, business, MESH: Neovascularization, Pathologic, 030217 neurology & neurosurgery
Abstract

International audience; PURPOSE: To evaluate the sequential injection of a low-molecular-weight (gadoterate meglumine [Gd-DOTA], 0.5 kDa) and a macromolecular (P846, 3.5 kDa) contrast media in monitoring the effect of antitumor therapies (antiangiogenic therapy and/or microbeam radiation therapy [MRT]) on healthy brain tissue and implanted tumors. MATERIALS AND METHODS: Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Eighty male rats bearing 9L gliosarcoma were randomized into four groups: untreated, antiangiogenic (sorafenib) therapy, MRT, and both treatments. Magnetic resonance (MR) imaging was performed 1 day before and 1, 5, and 8 days after the start of the treatment. At all time points, vascular integrity to a macromolecular contrast medium (P846) and, 11 minutes 30 seconds later, to low-molecular-weight contrast medium (Gd-DOTA) was evaluated by using a dynamic contrast material-enhanced MR imaging approach. To quantify vessel wall integrity, areas under the signal intensity curves were computed for each contrast medium. Unpaired t tests and one-way analysis of variance were used for statistical analyses. RESULTS: Tumor vessels receiving antiangiogenic therapy became less permeable to the macromolecular contrast medium, but their permeability to the low-molecular-weight contrast medium remained unchanged. Healthy double-irradiated vessels became permeable to the low-molecular-weight contrast medium but not to the macromolecular contrast medium. CONCLUSION: Antiangiogenic therapy and MRT generate different effects on the extravasation of contrast medium in tumoral and healthy tissues. This study indicates that the use of a low-molecular-weight contrast medium and a macromolecular contrast medium provides complementary information and suggests that the use of two contrast media within the same MR imaging session is feasible.

Published
2010

11. Blood-brain barrier permeability to manganese and to Gd-DOTA in a rat model of transient cerebral ischaemia.: BBB permeability after transient cerebral ischemia

Author

Christoph Segebarth, Peggy Provent, Emmanuelle Grillon, Chantal Rémy, Olivier Montigon, Emmanuel L. Barbier, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and grant ‘Imagerie du Petit Animal' (CNRS/ INSERM/CEA)

Subjects
Male, Time Factors, MESH: Cerebral Angiography, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Contrast Media, Infarction, Vascular permeability, MESH: Rats, Sprague-Dawley, blood–brain barrier, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, MESH: Blood-Brain Barrier, 0302 clinical medicine, Heterocyclic Compounds, Occlusion, MESH: Animals, Stroke, Spectroscopy, medicine.diagnostic_test, MESH: Infarction, Middle Cerebral Artery, Infarction, Middle Cerebral Artery, stroke, Extravasation, transient cerebral ischaemia, medicine.anatomical_structure, Blood-Brain Barrier, Ischemic Attack, Transient, Reperfusion Injury, Anesthesia, manganese, Molecular Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cerebral angiography, MRI, MESH: Rats, MESH: Heterocyclic Compounds, MESH: Manganese, MESH: Diffusion Magnetic Resonance Imaging, Blood–brain barrier, Capillary Permeability, 03 medical and health sciences, MESH: Contrast Media, Organometallic Compounds, medicine, Animals, Radiology, Nuclear Medicine and imaging, business.industry, MESH: Time Factors, MESH: Capillary Permeability, MESH: Organometallic Compounds, medicine.disease, MESH: Male, Cerebral Angiography, Rats, MESH: Reperfusion, Disease Models, Animal, Diffusion Magnetic Resonance Imaging, Gd-DOTA, Reperfusion, Angiography, MESH: Reperfusion Injury, MESH: Disease Models, Animal, business, MESH: Ischemic Attack, Transient, 030217 neurology & neurosurgery
Abstract

International audience; Loss of integrity of the blood-brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion-weighted imaging, T1-weighted (T1 W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B, n = 9), and 2 h 30 min (group C, n = 10). For 17 animals (four in group A, six in group B, and seven in group C), MnCl2 and dimeglumine gadoterate (Gd-DOTA) were injected at 13 min and 34 min after recanalization, respectively. The 10 remaining animals (control groups) underwent the same acquisition protocols, but no contrast agents were injected. Cell damage was determined 1 h after recanalization on haematoxylin and eosin-stained sections. Our results indicate that in the middle cerebral artery occlusion model in the rat, changes in BBB permeability assessed by contrast agent extravasation occur within the first hour of reperfusion, even after an occlusion period not exceeding 30 min. No differences between BBB permeability to Gd-DOTA and Mn2+ were detected in our experimental conditions. The reduction in apparent diffusion coefficient during occlusion appears to be a good predictor of BBB modifications after reperfusion in this model.

Published
2008

12. High-resolution contrast-enhanced MRI of atherosclerosis with digital cardiac and respiratory gating in mice

Author

Jacques Felblinger, Hasan Alsaid, Odette Fokapu, Yannick Crémillieux, Emmanuelle Canet-Soulas, Zakaria Bendahmane, André Briguet, Catherine Desbleds-Mansard, Claire Corot, Maher Sabbah, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Biomécanique et génie biomédical (BIM), Centre National de la Recherche Scientifique (CNRS), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Guerbet Research, IPA Program - Rhône-Alpes Region, and Felblinger, Jacques

Subjects
Male, Image quality, Contrast Media, MESH: Magnetic Resonance Angiography, Gating, atherosclerotic plaque, cardiorespiratory gating, MESH: Signal Processing, Computer-Assisted, Signal, 030218 nuclear medicine & medical imaging, MESH: Atherosclerosis, Electrocardiography, 0302 clinical medicine, Heart Rate, Heterocyclic Compounds, Demodulation, Medicine, MESH: Animals, Respiratory system, MESH: Heart Rate, Image resolution, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Signal Processing, Computer-Assisted, contrast agent, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Reproducibility of Results, MESH: Artifacts, MESH: Respiratory Mechanics, Radiology, MESH: Image Enhancement, Artifacts, medicine.medical_specialty, mice, MESH: Heterocyclic Compounds, Sensitivity and Specificity, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Contrast Media, Organometallic Compounds, Animals, Radiology, Nuclear Medicine and imaging, aortic arch and carotids, MESH: Mice, Digital signal processing, business.industry, Reproducibility of Results, Cardiorespiratory fitness, MESH: Organometallic Compounds, Atherosclerosis, Image Enhancement, MESH: Sensitivity and Specificity, MESH: Male, MESH: Electrocardiography, Mice, Inbred C57BL, Respiratory Mechanics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Magnetic Resonance Angiography, 030217 neurology & neurosurgery, Biomedical engineering
Abstract

International audience; Atherosclerosis initially develops predominantly at the aortic root and carotid origin, where effective visualization in mice requires efficient cardiac and respiratory gating. The present study sought to first compare the high-resolution MRI gating performance of two digital gating strategies using: 1) separate cardiac and respiratory signals (double-sensor); and 2) a single-sensor cardiorespiratory signal (ECG demodulation), and second, to apply an optimized processing technique to dynamic contrast-enhanced (CE) carotid origin vessel-wall imaging in mice. High-resolution MR mouse heart and aortic arch images were acquired by ECG signal detection, digital signal processing, and gating signal generation modeled using Simulink (MathWorks, USA). Double-sensor gating used a respiratory sensor while single-sensor gating used breathing-modulated ECG to generate a demodulated respiratory signal. Pre- and postcontrast T(1)-weighted images were acquired to evaluate vessel-wall enhancement with a gadolinium blood-pool agent (P792; Guerbet, France) at the carotid origin in vivo in ApoE(-/-) and C57BL/6 mice, using the optimized cardiorespiratory gating processing technique. Both strategies provided images with improved spatial resolution, less artifacts, and 100% correct transistor-to-transistor logic (TTL) signals. Image quality allowed vessel-wall enhancement measurement in all the ApoE(-/-) mice, with maximal (32%) enhancement 27 min postinjection. The study demonstrated the efficiency of both cardiorespiratory gating strategies for dynamic contrast-enhanced vessel-wall imaging.

Published
2007

13. Prostate dynamic contrast-enhanced MRI with simple visual diagnostic criteria: is it reasonable?

Author

Alvine Bissery, Muriel Rabilloud, Denis Lyonnet, Marc Colombel, J.-M. Marechal, Olivier Rouvière, Florence Mège-Lechevallier, Alejandro Tonina Senes, N. Girouin, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Mécanismes et Transfert en Géologie (LMTG), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Applications des ultrasons à la thérapie, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_treatment, Biopsy, Contrast Media, MESH: Logistic Models, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Prostate cancer, MESH: Biopsy, 0302 clinical medicine, Prostate, Heterocyclic Compounds, Image Processing, Computer-Assisted, Neuroradiology, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Prostatectomy, General Medicine, Middle Aged, Magnetic Resonance Imaging, MESH: Image Processing, Computer-Assisted, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Dynamic contrast-enhanced MRI, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, medicine.medical_specialty, MESH: Heterocyclic Compounds, Sensitivity and Specificity, 03 medical and health sciences, MESH: Prostatectomy, MESH: Contrast Media, medicine, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Aged, MESH: Humans, business.industry, Cancer, Prostatic Neoplasms, Magnetic resonance imaging, MESH: Organometallic Compounds, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Logistic Models, MESH: Prostatic Neoplasms, business
Abstract

The purpose of this study was to evaluate the accuracy of prostate cancer localization with simple visual diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). A total of 46 consecutive patients with biopsy-proven prostate cancer underwent prostate 1.5 T MRI with pelvic phased-array coils before prostatectomy. Besides the usual T2-weighted sequences, a 30-s DCE sequence was acquired three times after gadoterate injection. On DCE images, all early enhancing lesions of the peripheral zone were considered malignant. In the central gland, only early enhancing lesions appearing homogeneous or invading the peripheral zone were considered malignant. Three readers specified the presence of cancer in 20 prostate sectors and the location of distinct tumors. Results were compared with histology; p0.05 was considered significant. For localization of cancer in the sectors, DCE imaging had a significantly higher sensitivity [logistic regression, odds ratio (OR): 3.9, p0.0001] and a slightly but significantly lower specificity (OR: 0.57, p0.0001). Of the tumors0.3 cc, 50-60% and 78-81% were correctly depicted with T2-weighted and DCE imaging, respectively. For both techniques, the depiction rate of tumors0.3 cc was significantly influenced by the Gleason score (most Gleason/=6 tumors were overlooked), but not by the tumor volume.DCE-MRI using pelvic phased-array coils and simple visual diagnostic criteria is more sensitive for tumor localization than T2-weighted imaging.

Published
2007

14. Stromal cell-derived factor-1alpha modulation of the excitability of rat substantia nigra dopaminergic neurones: presynaptic mechanisms

Author

Jean-Louis Nahon, S. Mélik Parsadaniantz, William Rostène, Carole Rovère, D. Skrzydelsi, Alice Guyon, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Les chimiokines et leurs récepteurs : fonctions cérébrales et neuroendocriniennes, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Male, Benzylamines, Patch-Clamp Techniques, Dopamine, Cyclams, MESH: GABA Antagonists, Biochemistry, Synaptic Transmission, Ion Channels, Membrane Potentials, GABA Antagonists, chemistry.chemical_compound, 0302 clinical medicine, Heterocyclic Compounds, MESH: Up-Regulation, MESH: Presynaptic Terminals, MESH: Animals, CXC chemokine receptors, Neurotransmitter, MESH: Receptors, GABA-A, 0303 health sciences, Dopaminergic, Glutamate receptor, MESH: Neural Inhibition, MESH: Glutamic Acid, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, Up-Regulation, Substantia Nigra, Tetrodotoxin, GABAergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chemokines, CXC, MESH: G Protein-Coupled Inwardly-Rectifying Potassium Channels, Sodium Channel Blockers, medicine.medical_specialty, Receptors, CXCR4, MESH: Rats, MESH: Heterocyclic Compounds, MESH: Substantia Nigra, Presynaptic Terminals, Glutamic Acid, Substantia nigra, MESH: Dopamine, Biology, MESH: Receptors, CXCR4, 03 medical and health sciences, Cellular and Molecular Neuroscience, Organ Culture Techniques, Internal medicine, MESH: Patch-Clamp Techniques, MESH: Synaptic Transmission, medicine, MESH: Membrane Potentials, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, G protein-coupled inwardly-rectifying potassium channel, Rats, Wistar, MESH: Chemokines, CXC, 030304 developmental biology, Neural Inhibition, MESH: Rats, Wistar, Receptors, GABA-A, MESH: Organ Culture Techniques, MESH: Male, Chemokine CXCL12, Rats, Endocrinology, nervous system, chemistry, G Protein-Coupled Inwardly-Rectifying Potassium Channels, MESH: Sodium Channel Blockers, MESH: Ion Channels, 030217 neurology & neurosurgery
Abstract

In rat substantia nigra (SN), Chemokine (CXC motif) receptor 4 (CXCR4) for the chemokine stromal cell-derived factor (SDF)-1alpha is expressed on dopaminergic (DA) neurones, but also on non-DA cells, suggesting presynaptic actions. Using whole-cell patch-clamp recordings in DA neurones of rat SN slices at a holding potential of -60 mV, we showed here that SDF-1alpha exerts multiple presynaptic effects. First, SDF-1alpha (10 nm) induced an increase in the frequency of spontaneous and miniature GABA(A) postsynaptic currents by presynaptic mechanisms, consistent with the presence of CXCR4 on GABAergic neurones of the SN, as revealed by immunocytochemistry. Second, SDF-1alpha (0.1-1 nm) induced a glutamatergic inward current resistant to tetrodotoxin (TTX), most probably the result of glutamate release from non-neuronal cells. This inward current was not blocked by the CXCR4 antagonist AMD 3100 (1 microm), consistent with the lack of CXCR4 on astrocytes as shown by immunocytochemistry under basal conditions. Finally, SDF-1alpha (10 nm) induced, via CXCR4, an outward G protein-activated inward rectifier (GIRK) current, which was TTX sensitive and prevented by application of the GABA(B) antagonist CGP55845A, suggesting GABA spillover on to GABA(B) receptors. Our results show that SDF-1alpha induces, via presynaptic mechanisms, alterations in the excitability of DA neurones as confirmed by current-clamp experiments.

Published
2006

15. Evaluation of antiangiogenic treatment effects on tumors' microcirculation by Bayesian physiological pharmacokinetic modeling and magnetic resonance imaging

Author

Bertrand Bessoud, Nathalie Siauve, Frédéric Y. Bois, Daniel Balvay, Charles-André Cuénod, Céline Brochot, Saidi, Vanessa, Institut National de l'Environnement Industriel et des Risques (INERIS), Laboratoire de Recherche en Imagerie (LRI), Faculté de Necker, Service de Radiologie, Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, Blood pool agent, Pathology, Contrast Media, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, Mice, 0302 clinical medicine, Heterocyclic Compounds, Neoplasms, MESH: Microcirculation, Medicine, MESH: Animals, MESH: Neoplasms, medicine.diagnostic_test, Neovascularization, Pathologic, Magnetic Resonance Imaging, MESH: Quinazolines, Dynamic contrast-enhanced MRI, Arterial blood, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Physiologically based pharmacokinetic modelling, Biodistribution, medicine.medical_specialty, MESH: Heterocyclic Compounds, MESH: Bayes Theorem, Biomedical Engineering, Biophysics, Mice, Nude, Microcirculation, 03 medical and health sciences, Pharmacokinetics, MESH: Contrast Media, Organometallic Compounds, MESH: Mice, Nude, Animals, Radiology, Nuclear Medicine and imaging, MESH: Mice, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Magnetic resonance imaging, Bayes Theorem, MESH: Organometallic Compounds, Triazoles, Xenograft Model Antitumor Assays, MESH: Male, MESH: Triazoles, Quinazolines, business, MESH: Neovascularization, Pathologic, 030217 neurology & neurosurgery, Neoplasm Transplantation, MESH: Neoplasm Transplantation, MESH: X
Abstract

International audience; A physiological pharmacokinetic (PBPK) model was used to estimate tumor microcirculation in nude mice with a grafted tumor. The kinetics of a rapid clearance blood pool agent, Vistarem, were investigated by dynamic MRI after bolus administration. Signal enhancements were recorded in arterial blood and in tumor tissue. To analyze these data, we developed a whole-body mathematical model of the agent's biodistribution using physiological parameters. The model included six compartments: arterial and venous plasma, tumor (split into capillaries and interstitium), and the rest of the body (also split into capillaries and interstitium). As an application, changes in tumor microcirculation parameters were evaluated in mice receiving either an antiangiogenic treatment (ZD4190) or a placebo. The analysis was performed in a Bayesian framework, and the model was fitted to experimental data using Markov Chain Monte Carlo techniques. Results showed a significant difference in tumor microcirculation between the two groups of mice when the microcirculation parameters are considered together. This whole-body physiological model enables to analyze jointly data in tumor tissue and in arterial blood. This leads to accurate estimates of microcirculation parameters and the evaluation of their uncertainty.

Published
2006

16. Optimization of a blood pool contrast agent injection protocol for MR angiography

Author

Denis Le Bihan, Philippe Robert, Claire Corot, Robin Santus, Xavier Violas, Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Human Brain Research Center [Kyoto] (HBRC), Kyoto University, Service Hospitalier Frédéric Joliot (SHFJ), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Guerbet Recherche, Guerbet, Guerbet Research, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and Kyoto University [Kyoto]

Subjects
Male, medicine.medical_specialty, MESH: Heterocyclic Compounds, Blood pool, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Swine, Gadolinium, chemistry.chemical_element, MESH: Rabbits, Contrast Media, Injection rate, MESH: Magnetic Resonance Angiography, 030218 nuclear medicine & medical imaging, Peak concentration, Injections, 03 medical and health sciences, 0302 clinical medicine, Bolus (medicine), Pharmacokinetics, Heterocyclic Compounds, MESH: Contrast Media, Organometallic Compounds, Medicine, MESH: Injections, Animals, Radiology, Nuclear Medicine and imaging, MESH: Animals, MESH: Swine, business.industry, Mr angiography, Experimental Animal Models, MESH: Organometallic Compounds, MESH: Male, chemistry, Radiology, Rabbits, Nuclear medicine, business, 030217 neurology & neurosurgery, Magnetic Resonance Angiography
Abstract

Purpose To design an ideal first-pass profile for MR angiography (MRA) by optimizing a multiphasic injection protocol based on two experimental animal models. Materials and Methods An equivalent contrast-enhanced (CE) MRA injection protocol was developed with controlled injection modalities (injection rate, volume, and dose) in rabbits and pigs. P792, a blood pool contrast agent, was injected in 17 male New Zealand rabbits and five farm pigs with variable injection schemes (mono- and multiphasic). From the gadolinium (Gd) blood concentration data, a simulation of an MR acquisition was performed to evaluate the impact of such an injection protocol on MR arterial signal and to select the best injection protocol. Results An empirical relationship between the arterial peak concentration and the injection parameters was found in the rabbits and pigs, allowing precise prediction of the first-pass profile. Of the four injection scheme strategies tested (standard bolus and bi-, tri-, and multiphasic injection protocols), the multiphasic “ramp” injection protocol provided the most optimal contrast agent pharmacokinetics with a durable plateau of concentration. Conclusion Ramp injection protocol provides an optimized first-pass profile for CE-MRA. J. Magn. Reson. Imaging 2005;21:611–619. © 2005 Wiley-Liss, Inc.

Published
2005

17. Frequency-shift based detection of BMS contrast agents using SSFP: potential for MRA

Author

Françoise Vaufrey, Jessica Dubois, Denis Le Bihan, Philippe Robert, Franck Lethimonnier, Département de radiothérapie, CRLCC Val d'Aurelle - Paul Lamarque, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Guerbet Recherche, Guerbet, Guerbet Research, Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, IFR de Neuroimagerie Fonctionnelle (IFR 49), Human Brain Research Center [Kyoto] (HBRC), Kyoto University [Kyoto], Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire Guerbet, Laboratoire Guerbet / Guerbet Research, and Le Bihan, Denis

Subjects
MESH: Heterocyclic Compounds, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, media_common.quotation_subject, Biomedical Engineering, Biophysics, Contrast Media, chemistry.chemical_element, MESH: Rabbits, MESH: Magnetic Resonance Angiography, Signal, Magnetic resonance angiography, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, MESH: Computer Simulation, Heterocyclic Compounds, MESH: Contrast Media, Organometallic Compounds, medicine, Animals, Contrast (vision), Frequency offset, Computer Simulation, Radiology, Nuclear Medicine and imaging, MESH: Animals, media_common, medicine.diagnostic_test, Phantoms, Imaging, MESH: Organometallic Compounds, Steady-state free precession imaging, Image Enhancement, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, MESH: Phantoms, Imaging, chemistry, Feasibility Studies, Rabbits, Bolus (digestion), MESH: Image Enhancement, MESH: Feasibility Studies, MESH: Neck, Magnetic Resonance Angiography, Neck, 030217 neurology & neurosurgery
Abstract

International audience; A novel mechanism of MRI contrast enhancement, based on the detection by a balanced steady-state free precession (SSFP) sequence of the proton resonance frequency shift induced by bulk magnetic susceptibility (BMS) contrast agents, was investigated. The potential for this contrast mechanism to image blood vessels was explored. The relaxation time and the frequency shift effects of gadolinium- and dysprosium-DOTA on SSFP signal was first simulated and evaluated on a water phantom at 1.5 T. In vitro, a 5-mM concentration in contrast agent induced a 20-Hz frequency shift, leading to a signal increase of 92% for Dy-DOTA, and a 10-Hz frequency shift, leading to a signal increase of 58% for Gd-DOTA at the reference frequency, taking into account the nonlinear SSFP signal response on frequency offset. The concept was then evaluated in vivo on anesthetized rabbits. Low doses of dysprosium-DOTA were injected in their vascular system, and imaging was performed at the level of neck vessels. Following a bolus injection, mean signal changes of 31%, 20% and 14% were observed in the carotid arteries, the vertebral veins and the jugular veins, respectively. The bolus peak times in arteries and veins were consistent with the rabbit vascular circulation. This frequency-shift based contrast mechanism presents interesting potential for contrast-enhanced MR angiography (CE-MRA) compared to usual relaxation-based contrast, but further investigations on reproducibility will be necessary.

Published
2005

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