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8. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

Author

Palfi, Stéphane, Gurruchaga, Jean Marc, Ralph, G Scott, Lepetit, Helene, Lavisse, Sonia, Buttery, Philip C, Watts, Colin, Miskin, James, Kelleher, Michelle, Deeley, Sarah, Iwamuro, Hirokazu, Lefaucheur, Jean Pascal, Thiriez, Claire, Fenelon, Gilles, Lucas, Cherry, Brugières, Pierre, Gabriel, Inanna, Abhay, Kou, Drouot, Xavier, Tani, Naoki, Kas, Aurelie, Ghaleh, Bijan, Le Corvoisier, Philippe, Dolphin, Patrice, Breen, David P, Mason, Sarah, Guzman, Natalie Valle, Mazarakis, Nicholas D, Radcliffe, Pippa A, Harrop, Richard, Kingsman, Susan M, Rascol, Olivier, Naylor, Stuart, Barker, Roger A, Hantraye, Philippe, Remy, Philippe, Cesaro, Pierre, and Mitrophanous, Kyriacos A

Published
2014
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11. Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase <scp>II</scp> Trial

Author

Bachoud-Lévi, Anne-Catherine, Schramm, Catherine, Remy, Philippe, Aubin, Ghislaine, Blond, Serge, Bocket, Laurence, Brugières, Pierre, Calvas, Fabienne, Calvier, Elisabeth, Cassim, François, Challine, Dominique, Gagou, Clarisse Scherer, De Langavant, Laurent Cleret, Collier, Francis, Cottencin, Olivier, David, Philippe, Damier, Philippe, Delliaux, Marie, Delmaire, Christine, Delval, Arnaud, Démonet, Jean‐François, Descamps, Philippe, Gaura, Véronique, Gohier, Bénédicte, Goldman, Serge, Haddad, Bassam, Izopet, Jacques, Jeny, Roland, Kerr-Conte, Julie, Krystowiak, Pierre, Lalanne, Christophe, Lavisse, Sonia, Lefaucheur, Jean‐Pascal, Lemoine, Laurie, Levivier, Marc, Lotterie, Jean‐Albert, Lunel‐Fabiani, Françoise, Maison, Patrick, Massager, Nicolas, Massart, Renaud, Menei, Philippe, Montero‐Menei, Claudia, Neveu, Isabelle, Parant, Olivier, Pautot, Vivien, Payoux, Pierre, Péréon, Yann, Rialland, Amandine, Rosser, Anne, Rouard, Hélène HR, Schmitz, David, Simonetta‐Moreau, Marion, Simonin, Clémence, Slama, Hichem, Sol, Jean‐Christophe, Supiot, Frédéric, Tanguy, Jean‐Yves, Tenenbaum, Liliane, Verny, Christophe, Youssov, Katia, Peschanski, Marc, Audureau, Etienne, Palfi, Stéphane, Hantraye, Philippe, Centre de référence maladie de Huntington, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IMRB - 'NeuroPsychologie Interventionnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris sciences et lettres (PSL), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AOM00139 and AOM04021 Direction de la Recherche Clinique, Association Française contre les Myopathies., Collaborators : on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group : Catherine Schramm, Philippe Remy, Ghislaine Aubin, Serge Blond, Laurence Bocket, Pierre Brugières, Fabienne Calvas, Elisabeth Calvier, François Cassim, Dominique Challine, Clarisse Scherer Gagou, Laurent Cleret de Langavant, Francis Collier, Olivier Cottencin, Philippe David, Philippe Damier, Marie Delliaux, Christine Delmaire, Arnaud Delval, Jean-François Démonet, Philippe Descamps, Véronique Gaura, Bénédicte Gohier, Serge Goldman, Bassam Haddad, Jacques Izopet, Roland Jeny, Julie Kerr-Conte, Pierre Krystowiak, Christophe Lalanne, Sonia Lavisse, Jean-Pascal Lefaucheur, Laurie Lemoine, Marc Levivier, Jean-Albert Lotterie, Françoise Lunel-Fabiani, Patrick Maison, Nicolas Massager, Renaud Massart, Philippe Menei, Claudia Montero-Menei, Isabelle Neveu, Olivier Parant, Vivien Pautot, Pierre Payoux, Yann Pereon, Amandine Rialland, Anne Rosser, Hélène Rouard, David Schmitz, Marion Simonetta-Moreau, Clémence Simonin, Hichem Slama, Jean-Christophe Sol, Frédéric Supiot, Jean-Yves Tanguy, Liliane Tenenbaum, Christophe Verny, Katia Youssov, Marc Peschanski, Etienne Audureau, Stéphane Palfi, Philippe Hantraye., and Montero-Menei, claudia

Subjects
0301 basic medicine, medicine.medical_specialty, Neurology, Huntington s disease, MIG-' HD, Cell- and Tissue-Based Therapy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Huntington's disease, Randomized controlled trial, law, Internal medicine, medicine, Humans, Stage (cooking), Adverse effect, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, business.industry, phase 2 trial, Neurodegenerative Diseases, Sciences bio-médicales et agricoles, medicine.disease, Confidence interval, Transplantation, Huntington Disease, 030104 developmental biology, Neurology (clinical), cell therapy, business, 030217 neurology & neurosurgery
Abstract

Background\ud Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.\ud \ud Methods\ud Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.\ud \ud Results\ud Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.\ud \ud Conclusion\ud No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society

Published
2020
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15. Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial

Author

Bachoud-Lévi, Anne-Catherine, Schramm, Catherine, Remy, Philippe, Aubin, Ghislaine, Blond, Serge, Bocket, Laurence, Brugières, Pierre, Calvas, Fabienne, Calvier, Elisabeth, Cassim, François, Challine, Dominique, Gagou, Clarisse Scherer, De Langavant, Laurent Cleret, Collier, Francis, Cottencin, Olivier, David, Philippe, Damier, Philippe, Delliaux, Marie, Delmaire, Christine, Delval, Arnaud, Démonet, Jean‐François, Descamps, Philippe, Gaura, Véronique, Gohier, Bénédicte, Goldman, Serge, Haddad, Bassam, Izopet, Jacques, Jeny, Roland, Kerr-Conte, Julie, Krystowiak, Pierre, Lalanne, Christophe, Lavisse, Sonia, Lefaucheur, Jean‐Pascal, Lemoine, Laurie, Levivier, Marc, Lotterie, Jean‐Albert, Lunel‐Fabiani, Françoise, Maison, Patrick, Massager, Nicolas, Massart, Renaud, Menei, Philippe, Montero‐Menei, Claudia, Neveu, Isabelle, Parant, Olivier, Pautot, Vivien, Payoux, Pierre, Péréon, Yann, Rialland, Amandine, Rosser, Anne, Rouard, Hélène HR, Schmitz, David, Simonetta‐Moreau, Marion, Simonin, Clémence, Slama, Hichem, Sol, Jean‐Christophe, Supiot, Frédéric, Tanguy, Jean‐Yves, Tenenbaum, Liliane, Verny, Christophe, Youssov, Katia, Peschanski, Marc, Audureau, Etienne, Palfi, Stéphane, Hantraye, Philippe, Bachoud-Lévi, Anne-Catherine, Schramm, Catherine, Remy, Philippe, Aubin, Ghislaine, Blond, Serge, Bocket, Laurence, Brugières, Pierre, Calvas, Fabienne, Calvier, Elisabeth, Cassim, François, Challine, Dominique, Gagou, Clarisse Scherer, De Langavant, Laurent Cleret, Collier, Francis, Cottencin, Olivier, David, Philippe, Damier, Philippe, Delliaux, Marie, Delmaire, Christine, Delval, Arnaud, Démonet, Jean‐François, Descamps, Philippe, Gaura, Véronique, Gohier, Bénédicte, Goldman, Serge, Haddad, Bassam, Izopet, Jacques, Jeny, Roland, Kerr-Conte, Julie, Krystowiak, Pierre, Lalanne, Christophe, Lavisse, Sonia, Lefaucheur, Jean‐Pascal, Lemoine, Laurie, Levivier, Marc, Lotterie, Jean‐Albert, Lunel‐Fabiani, Françoise, Maison, Patrick, Massager, Nicolas, Massart, Renaud, Menei, Philippe, Montero‐Menei, Claudia, Neveu, Isabelle, Parant, Olivier, Pautot, Vivien, Payoux, Pierre, Péréon, Yann, Rialland, Amandine, Rosser, Anne, Rouard, Hélène HR, Schmitz, David, Simonetta‐Moreau, Marion, Simonin, Clémence, Slama, Hichem, Sol, Jean‐Christophe, Supiot, Frédéric, Tanguy, Jean‐Yves, Tenenbaum, Liliane, Verny, Christophe, Youssov, Katia, Peschanski, Marc, Audureau, Etienne, Palfi, Stéphane, and Hantraye, Philippe

Abstract

info:eu-repo/semantics/published

Published
2020

16. Assessment of simplified methods for quantification of [18F]-DPA-714 using 3D whole-brain TSPO immunohistochemistry in a non-human primate

Author

Van Camp, Nadja, primary, Balbastre, Yaël, additional, Herard, Anne-Sophie, additional, Lavisse, Sonia, additional, Tauber, Clovis, additional, Wimberley, Catriona, additional, Guillermier, Martine, additional, Berniard, Aurélie, additional, Gipchtein, Pauline, additional, Jan, Caroline, additional, Badin, Romina Aron, additional, Delzescaux, Thierry, additional, Hantraye, Philippe, additional, and Bonvento, Gilles, additional

Published
2019
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17. Impact of Endothelial 18-kDa Translocator Protein on the Quantification of 18F-DPA-714

Author

Wimberley, Catriona, Lavisse, Sonia, Brulon, Vincent, Peyronneau, Marie-Anne, Leroy, Claire, Bodini, Benedetta, Remy, Philippe, Stankoff, Bruno, Buvat, Irène, and Bottlaender, Michel

Subjects
PET, 18F-DPA-714, TSPO, quantification, neuroinflammation
Abstract

18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.

Published
2017

19. Comparative test-retest variability of outcome parameters derived from brain [18F]FDG PET studies in non-human primates.

Author

Goutal, Sébastien, Tournier, Nicolas, Guillermier, Martine, Van Camp, Nadja, Barret, Olivier, Gaudin, Mylène, Bottlaender, Michel, Hantraye, Philippe, and Lavisse, Sonia

Subjects
STATISTICAL reliability, BODY temperature, PRIMATES, GROUP size, CEREBELLUM
Abstract

Introduction: Knowledge of the repeatability of quantitative parameters derived from [18F]FDG PET images is essential to define the group size and allow correct interpretation. Here we tested repeatability and accuracy of different [18F]FDG absolute and relative quantification parameters in a standardized preclinical setup in nonhuman primates (NHP). Material and methods: Repeated brain [18F]FDG scans were performed in 6 healthy NHP under controlled experimental factors likely to account for variability. Regional cerebral metabolic rate of glucose (CMRglu) was calculated using a Patlak plot with blood input function Semi-quantitative approaches measuring standard uptake values (SUV, SUV×glycemia and SUVR (SUV Ratio) using the pons or cerebellum as a reference region) were considered. Test-retest variability of all quantification parameters were compared in different brain regions in terms of absolute variability and intra-and-inter-subject variabilities. In an independent [18F]FDG PET experiment, robustness of these parameters was evaluated in 4 naive NHP. Results: Experimental conditions (injected dose, body weight, animal temperature) were the same at both imaging sessions (p >0.4). No significant difference in the [18F]FDG quantification parameters was found between test and retest sessions. Absolute variability of CMRglu, SUV, SUV×glycemia and normalized SUV ranged from 25 to 43%, 16 to 21%, 23 to 28%, and 7 to 14%, respectively. Intra-subject variability largely explained the absolute variability of all quantitative parameters. They were all significantly correlated to each other and they were all robust. Arterial and venous glycemia were highly correlated (r = 0.9691; p<0.0001). Conclusion: [18F]FDG test-retest studies in NHP protocols need to be conducted under well-standardized experimental conditions to assess and select the most reliable and reproducible quantification approach. Furthermore, the choice of the quantification parameter has to account for the transversal or follow-up study design. If pons and cerebellum regions are not affected, non-invasive SUVR is the most favorable approach for both designs. [ABSTRACT FROM AUTHOR]

Published
2020
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20. Assessment of simplified methods for quantification of [ 18 F]-DPA-714 using 3D whole-brain TSPO immunohistochemistry in a non-human primate.

Author

Van Camp, Nadja, Balbastre, Yaël, Herard, Anne-Sophie, Lavisse, Sonia, Tauber, Clovis, Wimberley, Catriona, Guillermier, Martine, Berniard, Aurélie, Gipchtein, Pauline, Jan, Caroline, Badin, Romina Aron, Delzescaux, Thierry, Hantraye, Philippe, and Bonvento, Gilles

Abstract

The 18 kDa translocator protein (TSPO) is the main molecular target to image neuroinflammation by positron emission tomography (PET). However, TSPO-PET quantification is complex and none of the kinetic modelling approaches has been validated using a voxel-by-voxel comparison of TSPO-PET data with the actual TSPO levels of expression. Here, we present a single case study of binary classification of in vivo PET data to evaluate the statistical performance of different TSPO-PET quantification methods. To that end, we induced a localized and adjustable increase of TSPO levels in a non-human primate brain through a viral-vector strategy. We then performed a voxel-wise comparison of the different TSPO-PET quantification approaches providing parametric [18F]-DPA-714 PET images, with co-registered in vitro three-dimensional TSPO immunohistochemistry (3D-IHC) data. A data matrix was extracted from each brain hemisphere, containing the TSPO-IHC and TSPO-PET data for each voxel position. Each voxel was then classified as false or true, positive or negative after comparison of the TSPO-PET measure to the reference 3D-IHC method. Finally, receiver operating characteristic curves (ROC) were calculated for each TSPO-PET quantification method. Our results show that standard uptake value ratios using cerebellum as a reference region (SUVCBL) has the most optimal ROC score amongst all non-invasive approaches. [ABSTRACT FROM AUTHOR]

Published
2020
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21. Generalization of endothelial modelling of TSPO PET imaging: Considerations on tracer affinities

Author

Rizzo, Gaia, primary, Veronese, Mattia, additional, Tonietto, Matteo, additional, Bodini, Benedetta, additional, Stankoff, Bruno, additional, Wimberley, Catriona, additional, Lavisse, Sonia, additional, Bottlaender, Michel, additional, Bloomfield, Peter S, additional, Howes, Oliver, additional, Zanotti-Fregonara, Paolo, additional, Turkheimer, Federico E, additional, and Bertoldo, Alessandra, additional

Published
2017
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24. 367. A Dopamine Gene Therapy for Advanced PD: 4 Years Phase I/II Clinical Update

Author

Palfi, Stéphane, primary, Gurruchaga, Jean Marc, additional, Ralph, Scott Gs, additional, Watts, Colin, additional, Buttery, Philip, additional, Lepetit, Helene, additional, Miskin, James, additional, Gouello, Gaetane, additional, Lavisse, Sonia, additional, Fenelon, Gilles, additional, Thiriez, Claire, additional, Brugières, Pierre, additional, Barker, Roger, additional, Hantraye, Philippe, additional, and Mitrophanous, Kyriacos, additional

Published
2016
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25. Validation of an automatic reference region extraction for the quantification of [18F]DPA-714 in dynamic brain PET studies.

Author

García-Lorenzo, Daniel, Lavisse, Sonia, Leroy, Claire, Wimberley, Catriona, Bodini, Benedetta, Remy, Philippe, Veronese, Mattia, Turkheimer, Federico, Stankoff, Bruno, and Bottlaender, Michel

Abstract

There is a great need for a non-invasive methodology enabling the quantification of translocator protein overexpression in PET clinical imaging. [18F]DPA-714 has emerged as a promising translocator protein radiotracer as it is fluorinated, highly specific and returned reliable quantification using arterial input function. Cerebellum gray matter was proposed as reference region for simplified quantification; however, this method cannot be used when inflammation involves cerebellum. Here we adapted and validated a supervised clustering (supervised clustering algorithm (SCA)) for [18F]DPA-714 analysis. Fourteen healthy subjects genotyped for translocator protein underwent an [18F]DPA-714 PET, including 10 with metabolite-corrected arterial input function and three for a test–retest assessment. Two-tissue compartmental modelling provided BPND AIF estimates that were compared to either BPND LoganSCA or BPND LoganCRB generated by Logan analysis (using supervised clustering algorithm extracted reference region or cerebellum gray matter). The supervised clustering algorithm successfully extracted a pseudo-reference region with similar reliability using classes that were defined using either all subjects, or separated into HAB and MAB subjects. BPND AIF, BPND LoganSCA and BPND LoganCRB were highly correlated (ICC of 0.91 ± 0.05) but BPND LoganSCA were ∼26% higher and less variable than BPND LoganCRB. Reproducibility was good with 5% variability in the test–retest study. The clustering technique for [18F]DPA-714 provides a simple, robust and reproducible technique that can be used for all neurological diseases. [ABSTRACT FROM AUTHOR]

Published
2018
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28. Differential Dopamine Receptor Occupancy Underlies L-DOPA-Induced Dyskinesia in a Rat Model of Parkinson's Disease.

Author

Sahin, Gurdal, Thompson, Lachlan, Lavisse, Sonia, Özgür, Merve, Rbah-Vidal, Latifa, Dollé, Frédéric, Hantraye, Philippe, Kirik, Deniz, Sahin, Gurdal, Thompson, Lachlan, Lavisse, Sonia, Özgür, Merve, Rbah-Vidal, Latifa, Dollé, Frédéric, Hantraye, Philippe, and Kirik, Deniz

Abstract

Dyskinesia is a major side effect of an otherwise effective L-DOPA treatment in Parkinson's patients. The prevailing view for the underlying presynaptic mechanism of L-DOPA-induced dyskinesia (LID) suggests that surges in dopamine (DA) via uncontrolled release from serotonergic terminals results in abnormally high level of extracellular striatal dopamine. Here we used high-sensitivity online microdialysis and PET imaging techniques to directly investigate DA release properties from serotonergic terminals both in the parkinsonian striatum and after neuronal transplantation in 6-OHDA lesioned rats. Although L-DOPA administration resulted in a drift in extracellular DA levels, we found no evidence for abnormally high striatal DA release from serotonin neurons. The extracellular concentration of DA remained at or below levels detected in the intact striatum. Instead, our results showed that an inefficient release pool of DA associated with low D2 receptor binding remained unchanged. Taken together, these findings suggest that differential DA receptor activation rather than excessive release could be the underlying mechanism explaining LID seen in this model. Our data have important implications for development of drugs targeting the serotonergic system to reduce DA release to manage dyskinesia in patients with Parkinson's disease.

Published
2014

30. Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging

Author

Lavisse, Sonia, primary, Guillermier, Martine, additional, Hérard, Anne-Sophie, additional, Petit, Fanny, additional, Delahaye, Marion, additional, Van Camp, Nadja, additional, Ben Haim, Lucile, additional, Lebon, Vincent, additional, Remy, Philippe, additional, Dollé, Frédéric, additional, Delzescaux, Thierry, additional, Bonvento, Gilles, additional, Hantraye, Philippe, additional, and Escartin, Carole, additional

Published
2012
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31. Early Quantitative Evaluation of a Tumor Vasculature Disruptive Agent AVE8062 Using Dynamic Contrast-Enhanced Ultrasonography

Author

Lavisse, Sonia, primary, Lejeune, Pascale, additional, Rouffiac, Valérie, additional, Elie, Nicolas, additional, Bribes, Estelle, additional, Demers, Brigitte, additional, Vrignaud, Patricia, additional, Bissery, Marie-Christine, additional, Brulé, Aude, additional, Koscielny, Serge, additional, Péronneau, Pierre, additional, and Lassau, Nathalie, additional

Published
2008
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33. In Vitro Echogenicity Characterization of Poly[lactide-coglycolide] (PLGA) Microparticles and Preliminary In Vivo Ultrasound Enhancement Study for Ultrasound Contrast Agent Application

Author

Lavisse, Sonia, primary, Paci, Angelo, additional, Rouffiac, Valerie, additional, Adotevi, Cecile, additional, Opolon, Paule, additional, Peronneau, Pierre, additional, Bourget, Philippe, additional, Roche, Alain, additional, Perricaudet, Michel, additional, Fattal, Elias, additional, and Lassau, Nathalie, additional

Published
2005
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34. Optimized Quantification of Translocator Protein Radioligand 18F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers

Author

Michel Bottlaender, Daniel García-Lorenzo, Marie-Anne Peyronneau, Benedetta Bodini, Bruno Stankoff, Philippe Remy, Sonia Lavisse, Bertrand Kuhnast, Claire Thiriez, Claude Comtat, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), 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)-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-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de neurologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), ANR-08-MNPS-0016,INFLASEP,Imagerie de l'inflammation intracérébrale dans les formes progressives de sclérose en plaques(2008), ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), lavisse, sonia, Maladies Neurologiques et Psychiatriques - Imagerie de l'inflammation intracérébrale dans les formes progressives de sclérose en plaques - - INFLASEP2008 - ANR-08-MNPS-0016 - MNP - VALID, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, and Université Paris-Saclay-Institut de Biologie François JACOB (JACOB)

Subjects
Volume of distribution, education.field_of_study, biology, Chemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Coefficient of variation, Population, Neurodegeneration, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, genotyped human, Pharmacology, medicine.disease, quantification, DPA-714, PET, In vivo, Radioligand, Translocator protein, biology.protein, medicine, Radiology, Nuclear Medicine and imaging, $^{18}$F-DPA-714, education, TSPO
Abstract

International audience; Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the $^{18}$F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. Methods: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent $^{18}$F-DPA-714 PET with arterial and venous sampling. $^{18}$F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1-and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V$_T$) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. Results: The distribution pattern of $^{18}$F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of 18 F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation , 5%). For each region of interest, V$_T$ was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V$_T$ calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. Conclusion: Gen-otyping of subjects is a prerequisite for a reliable quantification of $^{18}$F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate $^{18}$F-DPA-714 V T in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.

Published
2015
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35. Reactive Astrocytes Overexpress TSPO and Are Detected by TSPO Positron Emission Tomography Imaging

Author

Frédéric Dollé, Martine Guillermier, Nadja Van Camp, Carole Escartin, Gilles Bonvento, Sonia Lavisse, Thierry Delzescaux, Lucile Ben Haim, Marion Delahaye, Fanny Petit, Philippe Hantraye, Anne-Sophie Hérard, Philippe Remy, Vincent Lebon, Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), 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)-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-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), lavisse, sonia, Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB)

Subjects
Male, Pathology, Indoles, Ciliary neurotrophic factor, Rats, Sprague-Dawley, Radioligand Assay, 0302 clinical medicine, Acetamides, Receptor, 0303 health sciences, CD11b Antigen, biology, Microglia, General Neuroscience, Microfilament Proteins, Neurodegeneration, Articles, Magnetic Resonance Imaging, Cell biology, medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Protein Binding, Astrocyte, medicine.medical_specialty, Genetic Vectors, Antigens, Differentiation, Myelomonocytic, 03 medical and health sciences, Antigens, CD, Fluorodeoxyglucose F18, In vivo, Glial Fibrillary Acidic Protein, medicine, Translocator protein, Animals, Ciliary Neurotrophic Factor, RNA, Messenger, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroinflammation, 030304 developmental biology, Analysis of Variance, Calcium-Binding Proteins, Receptors, GABA-A, medicine.disease, Corpus Striatum, Rats, Astrocytes, Positron-Emission Tomography, biology.protein, Radiopharmaceuticals, Carrier Proteins, 030217 neurology & neurosurgery
Abstract

Astrocytes and microglia become reactive under most brain pathological conditions, making this neuroinflammation process a surrogate marker of neuronal dysfunction. Neuroinflammation is associated with increased levels of translocator protein 18 kDa (TSPO) and binding sites for TSPO ligands. Positron emission tomography (PET) imaging of TSPO is thus commonly used to monitor neuroinflammation in preclinical and clinical studies. It is widely considered that TSPO PET signal reveals reactive microglia, although a few studies suggested a potential contribution of reactive astrocytes. Because astrocytes and microglia play very different roles, it is crucial to determine whether reactive astrocytes can also overexpress TSPO and yield to a detectable TSPO PET signalin vivo. We used a model of selective astrocyte activation through lentiviral gene transfer of the cytokine ciliary neurotrophic factor (CNTF) into the rat striatum, in the absence of neurodegeneration. CNTF induced an extensive activation of astrocytes, which overexpressed GFAP and become hypertrophic, whereas microglia displayed minimal increase in reactive markers. Two TSPO radioligands, [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-[18F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide] and [11C]SSR180575 (7-chloro-N,N-dimethyl-5-[11C]methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), showed a significant binding in the lenti-CNTF-injected striatum that was saturated and displaced by PK11195 [N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)-isoquinoline-3-carboxamide]. The volume of radioligand binding matched the GFAP immunopositive volume. TSPO mRNA levels were significantly increased, and TSPO protein was overexpressed by CNTF-activated astrocytes. We show that reactive astrocytes overexpress TSPO, yielding to a significant and selective binding of TSPO radioligands. Therefore, caution must be used when interpreting TSPO PET imaging in animals or patients because reactive astrocytes can contribute to the signal in addition to reactive microglia.

Published
2012
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36. Impact of Endothelial 18-kDa Translocator Protein on the Quantification of 18 F-DPA-714.

Author

Wimberley C, Lavisse S, Brulon V, Peyronneau MA, Leroy C, Bodini B, Remy P, Stankoff B, Buvat I, and Bottlaender M

Subjects
Brain cytology, Brain diagnostic imaging, Brain metabolism, Female, Gene Expression Regulation, Humans, Image Processing, Computer-Assisted, Kinetics, Male, Middle Aged, Positron-Emission Tomography, Receptors, GABA genetics, Signal-To-Noise Ratio, Endothelial Cells metabolism, Fluorine Radioisotopes, Pyrazoles, Pyrimidines, Receptors, GABA metabolism
Abstract

18 F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18 F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18 F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter K b varied highly across brain regions. K b strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression ( r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes ( r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between K b and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of K b and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18 F-DPA-714 PET, especially in diseases that induce vascular change., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Published
2018
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