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79 results on '"Samuel Valable"'

1. Beyond lymphopenia, unraveling radiation-induced leucocyte subpopulation kinetics and mechanisms through modeling approaches

Author

Thao-Nguyen Pham, Julie Coupey, Serge M. Candeias, Viktoriia Ivanova, Samuel Valable, Juliette Thariat, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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 Grenoble Alpes (UGA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CNRS MITI 80 Prime, and Ligue Contre le Cancer

Subjects
[PHYS]Physics [physics], Cancer Research, Oncology, Radiotherapy, Myelosuppression, Lymphopenia, [SDV]Life Sciences [q-bio], Modeling, Leucopenia
Abstract

Leucocyte subpopulations in both lymphoid and myeloid lineages have a significant impact on antitumor immune response. While radiation-induced lymphopenia is being studied extensively, radiation effects on lymphoid and myeloid subtypes have been relatively less addressed. Interactions between leucocyte subpopulations, their specific radiation sensitivity and the specific kinetics of each subpopulation can be modeled based on both experimental data and knowledge of physiological leucocyte depletion, production, proliferation, maturation and homeostasis. Modeling approaches of the leucocyte kinetics that may be used to unravel mechanisms underlying radiation induced-leucopenia and prediction of changes in cell counts and compositions after irradiation are presented in this review. The approaches described open up new possibilities for determining the influence of irradiation parameters both on a single-time point of acute effects and the subsequent recovery of leukocyte subpopulations. Utilization of these approaches to model kinetic data in post-radiotherapy states may be a useful tool for further development of new treatment strategies or for the combination of radiotherapy and immunotherapy.

Published
2023

2. Magnetic resonance imaging of hypoxia in acute stroke: a cross‐validation study against FMISO‐positron emission tomography

Author

Samuel, Valable, Toutain, Jérôme, Divoux, Didier, Chazalviel, Laurent, Corroyer-Dulmont, Aurélien, Chakhoyan, Ararat, Guillouet, Stéphane, Bernaudin, Myriam, Barbier, Emmanuel, Touzani, Omar, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), 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)-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)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN)

Subjects
hypoxia, [SDV]Life Sciences [q-bio], tissue oxygenation, FMISO-PET, stroke, MRI
Abstract

CERVOXY; International audience; Acute ischemic stroke results in ischemic core surrounded by a tissue at risk, named the penumbra, which is potentially salvageable. One way to differentiate the tissues is to measure the hypoxia status. The purpose of the study is to correlate the abnormal brain tissue volume derived from magnetic resonance-based imaging of brain oxygen saturation (StO2-MRI) to the [18F]FMISO positron emission tomography (PET) volume for hypoxia imaging validation, and to analyse the ability of StO2-MRI to depict the different hypoxic tissue types in the acute phase of stroke.In a pertinent model of stroke in the rat, the volume of tissue with decreased StO2-MRI signal and that with increased uptake of [18F]FMISO were equivalent and correlated (r=0.706; p=0.015). The values of StO2 in the tissue at risk were significantly greater than those quantified in the core of the lesion, and less than those of the healthy tissue (52.3±2.0%; 43.3±1.9% and 67.9±1.4%, respectively). A threshold value of StO2 of ≈60% as the cut-off for the identification of the tissue at risk was calculated. Tissue volumes with reduced StO2-MRI correlated with the final lesion (r=0.964, p

Published
2023

3. The Reactive Species Interactome in the Brain

Author

Elodie A. Pérès, Samuel Valable, Elise Malard, Myriam Bernaudin, Laurent Chatre, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physiology, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Context (language use), Computational biology, Oxidative phosphorylation, Biology, medicine.disease_cause, Biochemistry, Interactome, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, RSI, Molecular Biology, Reactive nitrogen species, 030304 developmental biology, General Environmental Science, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, distress, Brain, Cell Biology, Reactive Nitrogen Species, Reactive carbonyl species, Oxidative Stress, chemistry, General Earth and Planetary Sciences, pathology, Identification (biology), eustress, Reactive Oxygen Species, Oxidation-Reduction, 030217 neurology & neurosurgery, Oxidative stress
Abstract

CERVOXY; International audience; Significance: Redox pioneer Helmut Sies attempted to explain reactive species' challenges faced by organelles, cells, tissues, and organs via three complementary definitions: (1) oxidative stress, i.e. the disturbance in the prooxidant-antioxidant defense balance in favor of the prooxidants, (2) oxidative eustress, the low physiological exposure to prooxidants, and (3) oxidative distress, the supraphysiological exposure to prooxidants. Recent Advances: Identification, concentration and interactions are the most important elements to improve our understanding of reactive species in physiology and pathology. In this context, the reactive species interactome (RSI) is a new multilevel redox regulatory system that identifies reactive species families, reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS), and integrates their interactions with their downstream biological targets.Critical issues: We propose a united view to fully combine reactive species identification, oxidative eustress and distress, and the RSI system. In this view, we also propose including the forgotten reactive carbonyl species (RCS), an increasingly rediscovered reactive species family related to the other reactive families, and key enzymes within the RSI. We focus on brain physiology and pathology to demonstrate why this united view should be considered.Future directions: More studies are needed for an improved understanding of the contributions of reactive species through their identification, concentration, and interactions, including in the brain. Appreciating the reactive species interactome in its entirety should unveil new molecular players and mechanisms in physiology and pathology in the brain and elsewhere.

Published
2021

4. Internalization study of nanosized zeolite crystals in human glioblastoma cells

Author

Charly Helaine, Hayriye Özçelik, Sarah Komaty, Abdallah Amedlous, Sajjad Ghojavand, Didier Goux, Richard Retoux, Svetlana Mintova, Samuel Valable, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire catalyse et spectrochimie (LCS), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and INCA PLBIO 11699

Subjects
Colloidal suspension, Cell uptake, Nanosized zeolite, Cytotoxicity, [SDV]Life Sciences [q-bio], Surfaces and Interfaces, General Medicine, Faujasite, Oxygen, Colloid and Surface Chemistry, Zeolites, [CHIM]Chemical Sciences, Humans, Tissue Distribution, Physical and Theoretical Chemistry, Glioblastoma, Hypoxia, Biotechnology
Abstract

CERVOXY; International audience; While the use of nanozeolites for cancer treatment holds a great promise, it also requires a better understanding of the interaction between the zeolite nanoparticles and cancer cells and notably their internalization and biodistribution. It is particularly important in situation of hypoxia, a very common situations in aggressive cancers, which may change the energetic processes required for cellular uptake. Herein, we studied, in vitro, the kinetics of the internalization process and the intracellular localization of nanosized zeolite X (FAU-X) into glioblastoma cells. In normoxic conditions, scanning electron microscopy (SEM) showed a rapid cell membrane adhesion of zeolite nanoparticles (< 5 min following application in the cell medium), occurring before an energy-dependent uptake which appeared between 1 h and 4 h. Additionally, transmission electron microscopy (TEM) and flow cytometry analyzes, confirmed that the zeolite nanoparticles accumulate over time into the cytoplasm and were mostly located into vesicles visible at least up to 6 days. Interestingly, the uptake of zeolite nanoparticles was found to be dependent on oxygen concentration, i.e. an increase in internalization in severe hypoxia (0.2 % of O2) was observed. No toxicity of zeolite FAU-X nanoparticles was detected after 24 h and 72 h. The results clearly showed that the nanosized zeolites crystals were rapidly internalized via energy-requiring mechanism by cancer cells and even more in the hypoxic conditions. Once the zeolite nanoparticles were internalized into cells, they appeared to be safe and stable and therefore, they are envisioned to be used as carrier of various compounds to target cancer cells.

Published
2022

5. Kinetics and oxygen dependence of uptake of nanozeolites by human glioblastoma cells

Author

Hélaine, C, Özçelik, Hayriye, Komaty, S., Amedlous, A., Ghojavand, Sajjad, Goux, Didier, Retoux, Richard, Mintova, Svetlana, Samuel, Valable, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire catalyse et spectrochimie (LCS), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2022

6. The physical activity attenuates the brain irradiation-induced cerebral and skeletal muscle injuries in the adult rat

Author

Bécam, Julie, Ropars, Gwenn, Dwiri, Fatima-Azzahra, Toutain, Jérôme, Chazalviel, Laurent, Naveau, Mikaël, Samuel, Valable, Bernaudin, Myriam, Touzani, Omar, Pérès, Elodie A., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2022

7. Incorporation of trivalent cations in NaX zeolite nanocrystals for the adsorption of O2 in the presence of CO2

Author

Sarah Komaty, Michael Badawi, Ayoub Daouli, Samuel Valable, Moussa Zaarour, Svetlana Mintova, Clément Anfray, Laboratoire catalyse et spectrochimie (LCS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Laboratoire de Physique et Chimie Théoriques (LPCT), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Denticity, Chemistry, [SDV]Life Sciences [q-bio], Inorganic chemistry, General Physics and Astronomy, Infrared spectroscopy, Ionic bonding, Sorption, 02 engineering and technology, Faujasite, engineering.material, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Adsorption, Physisorption, 13. Climate action, engineering, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, 0210 nano-technology, Zeolite
Abstract

CERVOXY COLL; International audience; The O2 and CO2 sorption properties of nanosized zeolite X with faujasite type structure through a partial ionic exchange of sodium (Na +) by trivalent cations (Gd 3+ and Ce 3+) were evaluated. Three faujasite samples were studied, the as-synthesized Na-X possessing Na + solely, and the modified samples Na-Gd-X and Na-Ce-X containing Gd 3+ (1.8 wt%) and Ce 3+ (0.82 wt%), respectively. Incorporating scarce amounts of trivalent cations modified the adsorption affinity of zeolites towards O2 and CO2 as demonstrated by in situ Fourier-transform infrared spectroscopy (FTIR). While Na-Ce-X encounters the highest O2 physisorption capacity, the Na-Gd-X is adsorbing the highest quantities of molecular CO2. All three samples exhibit the chemisorbed CO2 in the form of carbonates, while the Na-X stores carbonates in monodentate and polydentate forms, the Na-Gd-X and Na-Ce-X allow the formation of polydentate carbonates only. Density functional theory (DFT) calculations revealed that trivalent cations tend to adsorb gases through two cations simultaneously which explains the presence of polydentate carbonates exclusively in the corresponding modified zeolites. The DFT results confirmed the higher affinity of Na-Gd-X and Na-Ce-X nanocrystals towards O2 in the presence of CO2. The affinity of Na-Gd-X and Na-Ce-X nanocrystals towards O2 opens the door of their use as oxygen transporters for medical applications where CO2 is constantly present. The toxicity of the nanosized zeolites and their performance in O2 release are reported too.

Published
2020

8. Comparative preclinical study of the effect of proton therapy versus conventional radiotherapy on circulating leukocytes in a context of brain tumour irradiation

Author

Coupey, Julie, Pham, Thao Nguyen, Toutain, Jérôme, Hue, Erika, Hélaine, C, Saulnier, Romaric, Chazalviel, Laurent, Rousseau, Marc, Thariat, Juliette, Leblond, M.M., Samuel, Valable, Brunaud, Carole, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), LABÉO, Pôle d’analyses et de recherche de Normandie (LABÉO), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Normandie Université (NU)-Normandie Université (NU), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2022

9. Brain Tumor Models & MRI Applications

Author

Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], Brain tumor, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

CERVOXY; International audience

Published
2021

10. Comparaison de la sensibilité des astrocytes murins et humains à différentes modalités d’irradiation

Author

Pasquet, Nolwenn, Pérès, Elodie A., Petit, Edwige, Toutain, Jérôme, Bernaudin, Myriam, Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Brunaud, Carole

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

11. L’activité physique réduit la cachexie observée après irradiation cérébrale chez le rat

Author

Bécam, Julie, Ropars, Gwenn, Dwiri, Fatima-Azzahra, Toutain, Jérôme, Chazalviel, Laurent, Naveau, Mikaël, Samuel, Valable, Bernaudin, Myriam, Touzani, Omar, Pérès, Elodie A., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

12. Caractérisation de l’hypoxie dans les métastases cérébrales issues de cancer du poumon : de l’approche clinique à la pré-clinique

Author

Jade, Fantin, Aurélien, Corroyer-Dulmont, Samuel, Valable, Toutain, Jérôme, Sylvain, Teulier, Céline, Bazille, Levallet, Jérôme, Françoise, Chapon, Levallet, Guénaëlle, Bernaudin, Myriam, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and Brunaud, Carole

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2021

13. Modèle préclinique de radiotoxicité cérébrale : évaluation longitudinale et multiparamétrique des atteintes tissulaires et cognitives chez le rat adulte

Author

Pérès, Elodie A., Ropars, Gwenn, Dwiri, Fatima-Azzahra, Carole, Brunaud, Toutain, Jérôme, Naveau, Mikaël, Petit, Edwige, Samuel, Valable, Bernaudin, Myriam, Touzani, Omar, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

14. L’IRM de diffusion du muscle squelettique : une méthode pertinente pour détecter les effets à distance induits par l'irradiation cérébrale chez le rat

Author

Julie, Bécam, Gwenn, Ropars, Fatima-Azzahra, Dwiri, Jérôme, Toutain, Laurent, Chazalviel, Mikaël, Naveau, Samuel, Valable, Myriam, Bernaudin, Omar, Touzani, Elodie A., Pérès, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

15. Intérêt de l'IRM multiparamétrique pour détecter les lésions cérébrales induites par l'irradiation chez le rat

Author

Carole, Brunaud, Samuel, Valable, Fatima-Azzahra, Dwiri, Gwenn, Ropars, Jérôme, Toutain, Mikaël, Naveau, Marianne, Léger, Thomas, Freret, Myriam, Bernaudin, Omar, Touzani, Elodie A., Pérès, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

16. Cartographie simultanée de la vascularisation, de l'hypoxie et de la prolifération à l'aide de l’IRM de perfusion, la TEP au 18F-FMISO et au 18F-FLT, en relation avec la prise de contraste dans les glioblastomes

Author

Cécile Perrio, Myriam Bernaudin, Stéphane Guillouet, David Hassanein Berro, J M Derlon, Samuel Valable, Mathieu Hatt, Solène Collet, Jean-Sébastien Guillamo, Jean-Marc Constans, Ararat Chakhoyan, Emmanuèle Lechapt-Zalcman, Dimitris Visvikis, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Départment de Neuroradiologie [CHU Caen], Laboratoire d'Anatomie Pathologique [CHU Caen], Service de Neuropathologie [Paris], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-GHU Paris Psychiatrie et Neurosciences, Laboratoire de Traitement de l'Information Medicale (LaTIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
03 medical and health sciences, 0302 clinical medicine, Radiological and Ultrasound Technology, [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, Neurology (clinical), 030217 neurology & neurosurgery, 030218 nuclear medicine & medical imaging
Abstract

CERVOXY-LDM TEP; International audience; Introduction L'IRM conventionnelle joue un rôle clé dans la prise en charge des patients atteints de glioblastomes, cependant, l’IRM multiparamétrique et la TEP pourraient fournir des informations supplémentaires en identifiant les régions à haut risque de récidive. Dans cette étude, nous nous sommes intéressés à la prolifération, l'hypervascularisation et l'hypoxie, considérées comme des facteurs de mauvais pronostic. Elles ont été évaluées en mesurant respectivement la captation du 18F-FLT, le rCBV et la captation du 18F-FMISO et comparées à la prise de contraste (PC) sur la séquence T1w-Gd.Méthodes Une IRM de perfusion (31 patients), une TEP au 18F-FLT (20 patients) et/ou une TEP 18F-FMISO (20 patients, dont 9 ayant eu les deux radiotraceurs), ont été réalisées en préopératoire. Les volumes et les hotspots (5% max de chaque volume) ont été segmentés semi-automatiquement sur les SUV des TEP 18F-FLT et 18F-FMISO, ainsi que sur les rCBV. Le pourcentage des volumes et des hotspots en dehors de la PC, a été calculé.Résultats Toutes les tumeurs ont montré une prolifération, une hypervascularisation et des régions hypoxiques élevées. Les volumes superposés sur les images T1w-Gd ont montré que certaines régions prolifératives, d'hypervascularisation et d'hypoxie s'étendaient au-delà de la PC, mais avec des différences marquées entre les patients. Les plages de volume périphérique en dehors de la PC étaient [1,6% - 155,5%], [1,5% - 89,5%] et [3,1% - 78,0%] pour 18F-FLT, rCBV et 18F-FMISO respectivement. Tous les patients avaient des hotspots hyperprolifératifs en dehors de la PC, tandis que les hotspots d'hypervascularisation et d'hypoxie étaient principalement détectés dans la PC.Conclusion L'analyse spatiale des cartographies multimodales avec les volumes segmentés et les hotspots fournit des informations précieuses pour optimiser la prise en charge et le traitement des glioblastomes.

Published
2021

17. Caractérisation de l’hypoxie et stratégies pour lever la radiorésistance dans les glioblastomes et les métastases cérébrales

Author

Bernaudin, Myriam, Berro David, Hassanein, Collet, Solène, Corroyer-Dulmont, Aurélien, Leblond M, Marine, Emery, Evelyne, Pérès, Elodie A., Levallet, Guénaëlle, Pasquet, Nolwenn, Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Brunaud, Carole, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), and Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience; L’hypoxie est un élément central de la croissance tumorale, impliquée aussi bien dans la progression tumorale que dans la résistance aux traitements conventionnels. Nos recherches visent à aborder l’hypoxie par plusieurs approches. Tout d’abord, nous cherchons à caractériser de l’échelle préclinique à l’échelle clinique, l’hypoxie et ses relations avec les cellules tumorales mais aussi avec leur microenvironnement dont la vascularisation, l’inflammation. Pour cela, nous utilisons des marqueurs histo-moléculaires mais également l’imagerie multimodale (IRM, TEP) pour évaluer l’hétérogénéité tumorale interpatient mais également spatiale des tumeurs cérébrales primitives de haut grade mais également des métastases cérébrales (Bekaert et al., 2017; Ponte et al., 2017; Pérès et al., 2019 ; Collet S et al., 2021 ; Corroyer-Dulmont A et al., 2021). En parallèle, nous développons des stratégies visant à contourner les effets de l’hypoxie sur la résistance aux traitements et en particulier, la radiothérapie. A ce titre, nous nous intéressons à l’hadronthérapie. Ainsi, nous avons pu montrer in vitro que les ions carbone sont plus efficaces que les photons sur les cellules tumorales hypoxiques (Valable S et al., 2020). Nous évaluons l’impact de l’hadronthérapie avec ou sans traitements combinés sur le caractère souche des cellules tumorales connu pour participer à cette radiorésistance induite par l’hypoxie. Nous développons également des stratégies pour réoxygéner et/ou radiosensibiliser les tumeurs. A titre d’exemple, nous avons récemment utilisé une stratégie nanoparticulaire afin de réoxygéner les glioblastomes (Anfray et al., 2020) mais aussi apporter du gadolinium, utilisé comme agent de radiosensibilisation. Des études sont actuellement en cours pour évaluer l’efficacité de cette approche théranostique que ce soit in vitro sur les cellules tumorales mais aussi in vivo chez le rongeur.En conclusion, nos travaux de recherche combinent des approches cellulaires aux études cliniques en passant par des études précliniques afin d’identifier l’hypoxie dans différents types de tumeurs cérébrales (glioblastomes, métastases cérébrales) et de développer des stratégies visant à atténuer les effets de l’hypoxie sur la résistance aux traitements.

Published
2021

18. Simultaneous mapping of vasculature, hypoxia and proliferation using DSC-MRI, 18F-FMISO PET, and 18F-FLT PET in relation to contrast enhancement in newly diagnosed glioblastoma

Author

Collet, Solène, Guillamo, Jean Sébastien, Berro, David Hassanein, Chakhoyan, Ararat, Constans, Jean-Marc, Lechapt-Zalcman, Emmanuèle, Derlon, Jean-Michel, Hatt, Mathieu, Visvikis, Dimitris, Guillouet, Stéphane, Perrio, Cécile, Bernaudin, Myriam, Samuel, Valable, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Neurology [UCLA], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), CHU Amiens-Picardie, Laboratoire d'Anatomie Pathologique [CHU Caen], Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), 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)-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)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Couteau, Florence, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT)

Subjects
[SDV] Life Sciences [q-bio], Glioblastoma, PET, Vascular, [SDV]Life Sciences [q-bio], Proliferation, [CHIM] Chemical Sciences, Vasculature, [CHIM]Chemical Sciences, Oncology: Brain, Hypoxia, MRI
Abstract

CERVOXY/LDM TEP COLL; International audience; Conventional MRI plays a key role in the management of patients with high grade glioma but multiparametric MRI and PET tracers could provide further information to better characterize the tumor metabolism and heterogeneity, by identifying the regions having a high risk of recurrence. In this study, we focused on the proliferation, hypervascularization and hypoxia, all factors considered as factors of poor prognosis. They were assessed by measuring the uptake of 18F-FLT, the rCBV maps and the uptake of 18F-FMISO, respectively. For each modality, the volumes and high uptake sub-volumes (hotspots) were semi-automatically segmented and compared to contrast enhancement (CE) volume on T1w-Gd images, commonly used in the management of patient with glioblastoma. Methods: DSC MRI (31 patients), 18F-FLT PET (20 patients) and/or 18F-FMISO PET (20 patients), for a total of 31 patients, were performed on pre-operative glioblastoma patients. Volumes and hotspots were segmented on SUV maps for 18F-FLT (using FLAB) and 18F-FMISO (using mean contralateral + 3.3 SD) PET and on rCBV maps (using mean contralateral + 1.96 SD) for DSC MRI and overlaid on T1w-Gd images. For each modality, the percentage of peripheral volumes and the peripheral hotspot outside the CE volume were calculated. Results: All tumors showed high proliferation, hypervascularization and hypoxic regions. Images also showed pronounced heterogeneity of both tracers uptake and rCBV maps, within each individual case. Overlaid volumes on T1w-Gd images showed that some proliferative, hypervascularization and hypoxic regions extended beyond the CE volume but with marked differences between patients. The ranges of peripheral volume outside the CE volume were [1.6% - 155.5 %], [1.5% - 89.5%] and [3.1% - 78.0%] for 18F-FLT, rCBV and 18F-FMISO respectively. All patients had hyperproliferative hotspots outside CE volume, whereas hotspots of hypervasculature and hypoxia were mainly detected within the enhancing region. Conclusion: The spatial analysis of the multiparametric maps with the segmented volumes and hotspots provides valuable information to optimize the management and treatment of the patients with glioblastoma.

Published
2021

19. Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy

Author

Aurélien Corroyer-Dulmont, Cécile Perrio, Didier Divoux, Guénaëlle Levallet, Méziane Ibazizène, Stéphane Guillouet, Jérôme Levallet, Samuel Valable, Jade Fantin, Jérôme Toutain, Louisa Barré, Elise Letissier, Sylvain Teulier, Françoise Chapon, Nicola R. Sibson, Sébastien Serres, Céline Bazille, Laurent Chatre, Myriam Bernaudin, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de pneumologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département de Pathologie [CHU Caen], School of Life Sciences, University of Nottingham, UK (UON), Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford [Oxford], Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Oncology [Oxford, UK] (CRUK/MRC), and University of Oxford

Subjects
Cancer microenvironment, medicine.medical_specialty, Lung Neoplasms, Cancer therapy, [SDV]Life Sciences [q-bio], Science, medicine.medical_treatment, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, medicine, Pimonidazole, Animals, Humans, Registries, Lung cancer, 030304 developmental biology, Aged, 0303 health sciences, Multidisciplinary, Tumor hypoxia, Radiotherapy, business.industry, Brain Neoplasms, Hypoxia (medical), Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Rats, Radiation therapy, CNS cancer, 030220 oncology & carcinogenesis, Cancer research, Medicine, Tumor Hypoxia, Neurosurgery, medicine.symptom, business, Immunostaining, Radiotherapy, Image-Guided
Abstract

Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth.

Published
2021

20. Copper exchanged FAU nanozeolite as non-toxic nitric oxide and carbon dioxide gas carrier

Author

Valentin Valtchev, Charly Hélaine, Clément Anfray, Richard Retoux, Valerie Ruaux, Sarah Komaty, Kamila Goldyn, Samuel Valable, Svetlana Mintova, Laboratoire catalyse et spectrochimie (LCS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)

Subjects
biomedical applications, non-toxic, [SDV]Life Sciences [q-bio], Metal-exchanged nanozeolites, Sodium, chemistry.chemical_element, 02 engineering and technology, gas adsorption, 010402 general chemistry, 7. Clean energy, 01 natural sciences, Nitric oxide, chemistry.chemical_compound, Adsorption, [CHIM]Chemical Sciences, General Materials Science, Fourier transform infrared spectroscopy, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Copper, 0104 chemical sciences, chemistry, gas carrier, Mechanics of Materials, Carbon dioxide, 0210 nano-technology, Nuclear chemistry
Abstract

CERVOXY COLL; International audience; A growing interest is currently directed to find an efficient NO and CO2 gas carriers for biomedical applications. The gas adsorption properties of sodium- (Na-X) and copper- (Cu-X) containing FAU nanozeolites toward nitric oxide and carbon dioxide were studied. The materials were fully characterised by XRD, TEM, ICP, DLS and in-situ FTIR. The as-prepared Na-X showed higher gas adsorption ability towards carbon dioxide, whereas the ion-exchanged Cu-X was more efficient adsorbent with regards to nitric oxide. In addition, the cytotoxicity tests disclosed that both nanozeolites have no toxicity making them suitable for further tests in biomedical field as gas transporters.

Published
2019

21. Conférence : 'De l’oxygène pour les tumeurs cérébrales : un nouvel espoir ?'

Author

Samuel, Valable, Couteau, Florence, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

CERVOXY

Published
2021

22. Ang2 overexpression optimizes the efficacy of radiochemotherapy in glioblastoma by acting in an autocrine and paracrine manner

Author

Hélaine, C, Ferré, Aurélie, Leblond, M.M., Pérès, Elodie A., Bernaudin, Myriam, Samuel, Valable, Petit, Edwige, Brunaud, Carole, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

23. Impact d'une irradiation cérébrale hémisphérique sur le tissu cérébral sain et la cognition : étude longitudinale et multiparamétrique chez le rat

Author

Dwiri, Fatima-Azzahra, Bécam, Julie, Carole, Brunaud, Chazalviel, Laurent, Samuel, Valable, Bernaudin, Myriam, Pérès, Elodie A., Touzani, Omar, Brunaud, Carole, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2021

24. Overcoming hypoxia-induced radioresistance of glioblastoma cells by hadrontherapy

Author

Pasquet, Nolwenn, Pérès, Elodie A., Toutain, Jérôme, Bernaudin, Myriam, Samuel, Valable, Brunaud, Carole, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), UNicaen, and ERRS Society

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2021

25. Angiopoietin-2 Combined with Radiochemotherapy Impedes Glioblastoma Recurrence by Acting in an Autocrine and Paracrine Manner: A Preclinical Study

Author

Myriam Bernaudin, M.M. Leblond, Aurélie Ferré, Edwige Petit, Charly Hélaine, Elodie A. Pérès, Samuel Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Cell, Inflammation, chemotherapy, lcsh:RC254-282, Article, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Immune system, vascularization, Medicine, Macrophage, Autocrine signalling, radiotherapy, Innate immune system, business.industry, glioblastoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, microenvironment, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, inflammation, 030220 oncology & carcinogenesis, Cancer research, Ectopic expression, angiopoietin-2, radiochemotherapy, medicine.symptom, business
Abstract

Simple Summary Glioblastoma (GB) is a highly aggressive brain tumor characterized by poor prognosis and high rate of recurrence in response to conventional treatments consisting of tumor resection and radiochemotherapy (RCT). The reasons for this therapeutic failure are mainly due to the complexity of GB biology and its environment. GB progression is highly dependent on its vascularization and inflammatory status. Besides, evidence showed that RCT also induces vascular change and inflammation. In GB patients, Angiopoietin-2 (Ang2), biomarker of poor prognosis is a crucial angiogenic factor also involved in inflammation. Our aim was to clarify the role of Ang2 in RCT-induced changes in the GB environment. To this end, we generated Ang2-overexpressing GL261 cells and characterized tumor progression, as well as inflammation and vascularization, in response to RCT. We showed that Ang2 delays tumor recurrence and makes a lasting improvement in animal survival when combined with conventional RCT. Abstract (1) We wanted to assess the impact of Ang2 in RCT-induced changes in the environment of glioblastoma. (2) The effect of Ang2 overexpression in tumor cells was studied in the GL261 syngeneic immunocompetent model of GB in response to fractionated RCT. (3) We showed that RCT combined with Ang2 led to tumor clearance for the GL261-Ang2 group by acting on the tumor cells as well as on both vascular and immune compartments. (4) In vitro, Ang2 overexpression in GL261 cells exposed to RCT promoted senescence and induced robust genomic instability, leading to mitotic death. (5) Coculture experiments of GL261-Ang2 cells with RAW 264.7 cells resulted in a significant increase in macrophage migration, which was abrogated by the addition of soluble Tie2 receptor. (6) Together, these preclinical results showed that, combined with RCT, Ang2 acted in an autocrine manner by increasing GB cell senescence and in a paracrine manner by acting on the innate immune system while modulating the vascular tumor compartment. On this preclinical model, we found that an ectopic expression of Ang2 combined with RCT impedes tumor recurrence.

Published
2020

26. Ruthenium tris(2,2′-bipyridyl) complex encapsulated in nanosized faujasite zeolite as intracellular localization tracer

Author

Aurélie Ferré, Moussa Zaarour, Samuel Valable, Svetlana Mintova, Sarah Komaty, Hayriye Özçelik, Laboratoire catalyse et spectrochimie (LCS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, intracellular tracer, [SDV]Life Sciences [q-bio], chemistry.chemical_element, 02 engineering and technology, engineering.material, 010402 general chemistry, 01 natural sciences, Ruthenium, Biomaterials, Crystallinity, Colloid and Surface Chemistry, 2,2'-Dipyridyl, nanocrystals, luminescence, Thermal stability, Surface charge, Zeolite, Faujasite, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Chemical engineering, Nanocrystal, chemistry, engineering, Zeolites, encapsulation, cytotoxicity, cell uptake, 0210 nano-technology, Luminescence
Abstract

CERVOXY; International audience; Designing zeolites for medical applications is a challenging task that requires introducing new functionalities without altering the intrinsic properties such as morphology, crystallinity, colloidal stability, surface charge, and porosity. Herein, we present the encapsulation of luminescent ruthenium-tris(2,2′-bipyridyl) complex in faujasite (FAU) zeolite nanocrystals (Ru(bpy)3-FAU) and their use as an intracellular localization tracer. Upon exciting the Ru(bpy)3-FAU zeolite at 450 nm, the sample gives rise to an orange-red emission at 628 nm, thus permitting its use for cellular imaging and localization of the zeolite nanoparticles. The nanosized Ru(bpy)3-FAU zeolite is characterized in terms of size, charge, crystallinity, morphology, porosity, thermal stability, and sorption capacity. The potential toxicity of Ru(bpy)3-FAU on U251-MG glioblastoma cells was evaluated. A safe concentration (50-100 µg/ml) for the Ru(bpy)3-FAU zeolite is identified. The luminescent properties of the ruthenium complex confined in the zeolite nanocrystals allow their localization in the U251-MG cells with a main accumulation in the cytoplasm. The Ru(bpy)3-FAU nanosized zeolite is a potential candidate for biological applications for being stable, safe, capable of loading respiratory gases, and easily probed in the cells owing to its luminescent properties.

Published
2020

27. Presse numérique CNRS : 'Nanocrystals to deliver oxygen to brain tumours'

Author

Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

CERVOXY; International audience

Published
2020

28. SRC Tyrosine Kinase Inhibitor and X-rays Combined Effect on Glioblastoma Cell Lines

Author

Filippo Torrisi 1, 2, Luigi Minafra 2, 3, Francesco P. Cammarata 2, Gaetano Savoca 2, Marco Calvaruso 2, Nunzio Vicario 1, Laura Maccari 4, Elodie A. Pérès 5, Hayriye Özçelik 5, Myriam Bernaudin 5, Lorenzo Botta 4, Giorgio Russo 2, Rosalba Parenti 1, Samuel Valable 5, Istituto Nazionale di Fisica Nucleare, Sezione di Catania (INFN), Università degli studi di Catania = University of Catania (Unict), University of Catania [Italy], Laboratori Nazionali del Sud (LNS), Istituto Nazionale di Fisica Nucleare (INFN), Lead Discovery Siena (LDS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Department of Biomedical and Biotechnological Sciences [Catania, Italy], Università degli studi di Catania [Catania], Institute of Molecular Bioimaging and Physiology, Consiglio Nazionale delle Ricerche (CNR), and Lead Discovery Siena s.r.l. (LDS)

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Tyrosine-kinase inhibitor, Histones, lcsh:Chemistry, 0302 clinical medicine, Cell Movement, Radiation, Ionizing, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, Brain Neoplasms, Chemistry, General Medicine, Prognosis, 3. Good health, Computer Science Applications, src-Family Kinases, 030220 oncology & carcinogenesis, medicine.symptom, ionizing radiation, Proto-oncogene tyrosine-protein kinase Src, Cell Survival, medicine.drug_class, DNA damage, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, combined treatments, Cell Line, Tumor, Radioresistance, medicine, Humans, Physical and Theoretical Chemistry, Protein Kinase Inhibitors, Molecular Biology, 030304 developmental biology, Chemotherapy, Radiotherapy, hypoxia, X-Rays, Organic Chemistry, Hypoxia (medical), Radiation therapy, Glioblastoma, Kinetics, Microscopy, Fluorescence, lcsh:Biology (General), lcsh:QD1-999, Oxygen enhancement ratio, Cancer research, Drug Screening Assays, Antitumor, Neoplasm Recurrence, Local
Abstract

Glioblastoma (GBM) is one of the most lethal types of tumor due to its high recurrence level in spite of aggressive treatment regimens involving surgery, radiotherapy and chemotherapy. Hypoxia is a feature of GBM, involved in radioresistance, and is known to be at the origin of treatment failure. The aim of this work was to assess the therapeutic potential of a new targeted c-SRC inhibitor molecule, named Si306, in combination with X-rays on the human glioblastoma cell lines, comparing normoxia and hypoxia conditions. For this purpose, the dose modifying factor and oxygen enhancement ratio were calculated to evaluate the Si306 radiosensitizing effect. DNA damage and the repair capability were also studied from the kinetic of &gamma, H2AX immunodetection. Furthermore, motility processes being supposed to be triggered by hypoxia and irradiation, the role of c-SRC inhibition was also analyzed to evaluate the migration blockage by wound healing assay. Our results showed that inhibition of the c-SRC protein enhances the radiotherapy efficacy both in normoxic and hypoxic conditions. These data open new opportunities for GBM treatment combining radiotherapy with molecularly targeted drugs to overcome radioresistance.

Published
2020
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29. Radionuclide spatial distribution and dose deposition for in vitro assessments of $^{212}$Pb-alphaVCAM-1 targeted alpha therapy

Author

Nicola R. Sibson, Katherine A. Vallis, Myriam Bernaudin, B.Q. Lee, Nadia Falzone, Aurélien Corroyer-Dulmont, Samuel Valable, Anne-Marie Frelin-Labalme, Thomas Roger, Grand Accélérateur National d'Ions Lourds (GANIL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and University of Oxford

Subjects
Reproducibility, Radionuclide, Materials science, Uniform distribution (continuous), targeted alpha therapy, dosimetry, [SDV]Life Sciences [q-bio], Monte Carlo method, Context (language use), General Medicine, Spatial distribution, α‐emitters, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Absorbed dose, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Dosimetry, 212Pb, clonogenic assay, Biological system, in vitro irradiations
Abstract

CERVOXY COLL; International audience; PurposeTargeted alpha therapy (TAT) takes advantage of the short‐range and high linear‐energy‐transfer of α‐particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α‐emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α‐emitting 212Pb coupled to an anti‐VCAM‐1 antibody (212Pb‐αVCAM‐1) and its evolution over time in the context of in vitro irradiations.MethodsTwo experimental setups were implemented without cells to measure α‐particle count rates and energy spectra in culture medium containing 15 kBq of 212Pb‐α‐VCAM‐1. Silicon detectors were placed above and below cell culture dishes for 20 hours. One of the dishes had a 2.5‐µm‐thick mylar‐base allowing easy detection of the α‐particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modelled and α‐energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212Pb‐αVCAM‐1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments.ResultsExperimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations.ConclusionThis study demonstrated that accurate dosimetry of α‐emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods.

Published
2020

30. 64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

Author

Louis-Paul Paty, Samuel Valable, Mickaël Bourgeois, Aurélien Vidal, Stéphane Guillouet, Méziane Ibazizène, Jérôme Toutain, Myriam Bernaudin, Louisa Barré, Didier Divoux, Michel Chérel, Elodie A. Pérès, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), GIP ARRONAX [Nantes], Université de Nantes (UN), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine, lcsh:R895-920, [SDV]Life Sciences [q-bio], Cell, PET radiotracers, Brain tumors, 03 medical and health sciences, Copper transporters, 0302 clinical medicine, In vivo, medicine, Radiology, Nuclear Medicine and imaging, Hypoxia, Original Research, business.industry, Transporter, Hypoxia (medical), medicine.disease, Cu-ATSM, In vitro, Astrogliosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Immunohistochemistry, medicine.symptom, business, 030217 neurology & neurosurgery, Ex vivo
Abstract

Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

Published
2019

31. Hadrontherapy Interactions in Molecular and Cellular Biology

Author

Elodie A. Pérès, Siamak Haghdoost, Sebastien Thureau, Jean-Louis Habrand, Aurélie Ferré, Michael Gérard, Carine Laurent, Sven Skog, Juliette Thariat, François Chevalier, Paul Lesueur, Jacques Balosso, Myriam Bernaudin, Mihaela Tudor, Yannick Saintigny, Samuel Valable, Mathieu Césaire, Edwige Petit, François Sichel, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), ARCHADE (Advanced Resource Centre for HADrontherapy in Europe), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Aliments Bioprocédés Toxicologie Environnements (ABTE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d'Accueil et de Recherche avec les Ions Accélérés (LARIA), 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), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Sino-Swed Molecular Bio-Medicine Research Institute (SSTK), Horia Hulubei National Institute of Physics and Nuclear Engineering (NIPNE), IFIN-HH, University of Bucharest (UniBuc), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), and Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Carbon therapy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Review, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], Catalysis, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, 0302 clinical medicine, Radioresistance, Neoplasms, hadrontherapy, medicine, Proton Therapy, Humans, cancer, Radiosensitivity, Physical and Theoretical Chemistry, Molecular Biology, Proton therapy, lcsh:QH301-705.5, Spectroscopy, 030304 developmental biology, 0303 health sciences, Particle therapy, Radiotherapy, business.industry, hypoxia, Organic Chemistry, Cancer, General Medicine, medicine.disease, 3. Good health, Computer Science Applications, Radiation therapy, radioresistance, lcsh:Biology (General), lcsh:QD1-999, particle therapy, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], business
Abstract

CERVOXY COLL; International audience; The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.

Published
2019

32. Effets de la surexpression de Ang2 dans la récidive du glioblastome après chimio-radiothérapie

Author

Hélaine, Charly, Ferré, Aurélie, Leblond, M.M., Aurélien, Corroyer-Dulmont, Pérès, E.A., Myriam, Bernaudin, Samuel, Valable, Edwige, Petit, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2019

33. An animal model to evaluate radiation-induced damage on the healthy brain

Author

Ropars, Gwenn, Dwiri, Fatima-Azzahra, Le Gal, Rozenn, Jérôme, Toutain, Bernaudin, Myriam, Samuel, Valable, Omar, Touzani, Pérès, E.A., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2019

34. Kinetics of radiation-induced motor and cognitive impairments in the adult rat model

Author

Ropars, Gwenn, Dwiri, Fatima-Azzahra, Le Gal, Rozenn, Jérôme, Toutain, Myriam, Bernaudin, Samuel, Valable, Omar, Touzani, Pérès, E.A., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

35. Is MRI sensitive enough to detect radiation-induced brain alterations?

Author

Dwiri, Fatima-Azzahra, Ropars, Gwenn, Jérôme, Toutain, Carole, Brunaud, Naveau, Mickael, Myriam, Bernaudin, Samuel, Valable, Omar, Touzani, Pérès, E.A., Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

36. Ang2 overexpression optimizes the efficacy of chemo-radiotherapy in glioblastoma

Author

Hélaine, Charly, Ferré, Aurélie, Leblond, M.M., Pérès, E.A., Myriam, Bernaudin, Samuel, Valable, Edwige, Petit, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

37. Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)

Author

M.M. Leblond, Z. Mintova, Charly Hélaine, Sarah Komaty, Samuel Valable, Edwige Petit, Myriam Bernaudin, Aurélie Ferré, H. Ozcelik, C. Anfray, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire catalyse et spectrochimie (LCS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0303 health sciences, Programmed cell death, medicine.diagnostic_test, Interferon type II, business.industry, [SDV]Life Sciences [q-bio], Hematology, Cell cycle, Molecular biology, In vitro, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Oncology, In vivo, 030220 oncology & carcinogenesis, Medicine, Macrophage, business, Interleukin 4, 030304 developmental biology, medicine.drug
Abstract

Background Glioblastoma (GB), a highly hypoxic brain tumor (Bekaert et al. 2017), is characterized by a massive macrophage (MΦ) infiltration (Lapa et al. 2015). Hypoxia triggers a shift to a pro-tumoral M2 phenotype in GB (Leblond et al. 2016). Thus, strategies aiming to reduce hypoxia could promote an anti-tumoral M1 phenotype. Among these reoxygenation strategies, we recently developed a new approach with zeolites nanoparticles. These zeolites are able to carry hyperoxic/hypercapnic gases and release them according to a hypoxic gradient. We have demonstrated that the charge balancing cation changes affinity to the gases but also the ability to track zeolite with MRI. Our objective is to study the reoxygenation efficacy of zeolites specifically in the GB and to evaluate their impact on tumor associated MΦ with in vitro and in vivo studies. Methods Faujasite zeolites (FAU, ∼20nm of diameter) were used and modified by ion exchange with various cations (Fe, Gd, Cu, Ag). GB model was obtained by orthotopic glioblastoma cells implantation (U251) in nude rats (ONCOModels/Unicaen). 7T MRI (Bruker/Cyceron) was used to follow zeolites after intravenous injection and for oxygen measurement. Murine bone marrow derived MΦ were prepared and polarized to M1 and M2 using LPS/IFNg or IL4 as previously described (Leblond et al. 2016). Zeolites were added in MΦ medium and their impact on MΦ were evaluated by crystal violet dye assay, flow cytometry (Plateau ICORE/Unicaen) and polarization assays. Results Our results show that zeolites are able to accumulate and release the carried gases specifically in the brain tumor leading to tumor reoxygenation. Regarding the effect on MΦ, our preliminary results show, in vitro, the safety of as-prepared zeolites or Fe, Gd or Cu dopped zeolites on M0, M1 and M2 MΦ cultures. Similarly, no alteration of the cell cycle was observed. As a positive control of cell death, the presence of Ag-dopped zeolites dramatically decreased M0 and M1 MΦ viability. Conclusions Zeolites can deliver oxygen to the brain tumor and may improve the effectiveness of conventional treatments. Zeolites do not exhibit toxicity on primary cultures of MΦ. Additional studies are underway to evaluate the effect of zeolites on the polarization of MΦ, both in vitro and in vivo. Legal entity responsible for the study The authors. Funding Region Normandie, CNRS, Universite de Caen Normandie, Ministere de l’Enseignement Superieur et de la Recherche, European Union-Fonds Europeen de Developpement Regional (FEDER), HABIONOR European project, co-funded by the Normandy County Council, the French State in the framework of the interregional development Contract “Vallee de la Seine” 2015-2020, ARCHADE, Federation pour la Recherche sur le Cerveau (FRC) et INCa (INCA-11699). Disclosure All authors have declared no conflicts of interest.

Published
2019

38. Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy

Author

Myriam Bernaudin, Aurélie Ferré, Edwige Petit, Charly Hélaine, Elodie A. Pérès, Samuel Valable, M.M. Leblond, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
Angiogenesis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Glioma, Medicine, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, Temozolomide, business.industry, Hematology, medicine.disease, 3. Good health, Radiation therapy, Vascular endothelial growth factor, [SDV] Life Sciences [q-bio], Vascular endothelial growth factor A, Oncology, chemistry, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, business, medicine.drug
Abstract

Background Glioblastoma (GB) are brain tumors with a poor prognosis despite multimodal treatment combining resection, chemotherapy (CT) and radiotherapy (RT). The rich vascularization of these tumors led to the introduction of anti-angiogenic therapy with most efforts focused on the vascular endothelial growth factor (VEGF). However, the angiopoietins (Ang) have emerged as alternative regulators of angiogenesis. In particular, in GB, Ang2 is up-regulated and stimulates tumor angiogenesis in concert with VEGF but also activates pro-angiogenic functions of macrophages. However, Ang2 functions are context-dependent. Therefore, we sought to elucidate the involvement of Ang2 in the interaction of glioma response to CT and RT, both therapeutic modalities known to alter tumor angiogenesis and inflammation. Methods To recapitulate high levels of Ang2 in GB patients, Ang2 was overexpressed in murine glioma cells (GL261-Ang2). Effects of Ang2 were studied on an orthotopic syngenic model of GB (GL261 cells) in response to combined CT/RT. C57bl/6 mice were co-treated with temozolomide (TMZ 10 mg/kg; i.p.) and brain tumors were irradiated with X-rays (4 Gy) at 7, 9 and 11 days post-cell injection. The tumor growth and its microenvironment were followed by MRI and immunohistology analyses. Results We showed that, in this model, the chronic overexpression of Ang2 does not modify tumor progression, but leads to a decrease in vessel density (-39±10%, p 3 months) compared with treated GL261 tumors (18±3 days). In vitro, no difference in the chemo-radiosensitivity of GL261 and GL261-Ang2 cells was noticed, suggesting a paracrine effect of Ang2 on the tumor microenvironment. Accordingly, we showed that Ang2 sensitizes the tumor vasculature to CT/RT and sustains inflammatory cells in the tumor microenvironment until 3 months post-treatment. Conclusions These results suggest that Ang2 might influence the therapeutic response of GB by acting on angiogenesis and inflammation. Legal entity responsible for the study E. Petit. Funding This study was funded by the Region Normandie, the Centre National de la Recherche Scientifique (CNRS), the Universite de Caen Normandie (UNICAEN), the European Union-Fonds Europeen de Developpement Regional (FEDER), ARCHADE, HABIONOR European project, la Federation pour la Recherche sur le Cerveau par l’operation Rotary «Espoir en tete » (FRC), EdNBise 497 - Normandie Universite. Disclosure All authors have declared no conflicts of interest.

Published
2019

39. VCAM-1 targeted alpha-particle therapy for early brain metastases

Author

Ole Tietz, Laurent Chazalviel, Anne Marie Frelin-Labalme, Samuel Valable, Manuel Sarmiento Soto, Jérôme Toutain, Myriam Bernaudin, Elodie A. Pérès, Katherine A. Vallis, Didier Divoux, Aurélien Corroyer-Dulmont, Nicola R. Sibson, Nadia Falzone, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Department of Oncology [Oxford, UK] (CRUK/MRC), University of Oxford [Oxford], Grand Accélérateur National d'Ions Lourds (GANIL), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Brunaud, Carole, University of Oxford, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Couteau, Florence, Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Mice, Nude, Vascular Cell Adhesion Molecule-1, Breast Neoplasms, Antibodies, Targeted therapy, early brain metastases, Mice, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cell Line, Tumor, Internal medicine, Carcinoma, medicine, AcademicSubjects/MED00300, Animals, Humans, External beam radiotherapy, Stage (cooking), 030304 developmental biology, VCAM-1, 0303 health sciences, alpha-particle therapy, Radiotherapy, Brain Neoplasms, business.industry, Brain, Histology, Lead Radioisotopes, Alpha Particles, medicine.disease, 3. Good health, Radiation therapy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Basic and Translational Investigations, Toxicity, AcademicSubjects/MED00310, Female, Neurology (clinical), business
Abstract

Background Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1). Methods Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT. Results 212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed. Conclusions The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.

Published
2019

40. Comparison between MRI-derived ADC maps and 18FLT-PET in pre-operative glioblastoma

Author

Jean-Sébastien Guillamo, Samuel Valable, J M Derlon, David Hassanein Berro, Louisa Barré, Solène Collet, Evelyne Emery, Jean-Marc Constans, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Départment de Neuroradiologie [CHU Caen], GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], and CCSD, Accord Elsevier

Subjects
Percentile, Cellularity, [SDV]Life Sciences [q-bio], 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Medicine, Radiology, Nuclear Medicine and imaging, Multiparametric Magnetic Resonance Imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Radiological and Ultrasound Technology, business.industry, medicine.disease, Pre operative, nervous system diseases, [SDV] Life Sciences [q-bio], body regions, ADC, MESH: Glioblastoma, MRI, ADC, 18FLT-PET, Cellularity, 18FLT-PET, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), business, Nuclear medicine, Glioblastoma, 030217 neurology & neurosurgery, MRI
Abstract

Background and purpose Among principal MRI sequences used for a better pre-therapeutic characterization of glioblastoma (GBM), DWI-derived ADC is expected to be a good parameter for the evaluation of cellularity, due to restricted water diffusivity. We aimed here to compare ADC maps to 18FLT-PET, a proliferation tracer, in GBM cases. Materials and methods Patients underwent 18FLT-PET, followed by multiparametric magnetic resonance imaging (MRI) just prior to surgery. We analysed in this study twenty GBM confirmed patients. The 5th percentile (5p) of the ADC values were thresholded to define the ADCmin ROI, while the 95th percentile (95p) of the SUV FLT values were used to define the FLTmax ROI. The statistical and spatial correlations between these two groups of ROIs were analyzed. Results We did not observe any significant correlations between ADCmin and FLTmax cut-off values (R2 = 0.0285), neither between ADCmin and FLTmax ROIs (mean Dice = 0.09 ± 0.12). Mean ADC values in the FLTmax defined ROI were significantly higher than the values in the ADCmin ROI (P Conclusions When comparing ADC maps to 18FLT uptake, we did not observe significant anatomical overlap nor correlation, between the regions of low ADC and high FLT disabling to clearly link ADC values to cellular proliferation. The exact significance of ADC maps in GBM has yet to be elaborated.

Published
2019

41. Multimodal and multiscale imaging for glioblastoma : interest for prognostic and assessment of treatment efficacy

Author

Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

42. Influence of Ang2 overexpression in the recurrence of glioblastoma after chemo-radiotherapy

Author

Hélaine, Charly, Ferré, Aurélie, Leblond, M.M., Aurélien, Corroyer-Dulmont, Pérès, E.A., Myriam, Bernaudin, Samuel, Valable, Edwige, Petit, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2019

43. Comparison of rodent and human astrocytes sensitivity and responses after irradiation

Author

Pasquet, Nolwenn, Pérès, E.A., Edwige, Petit, Samuel, Valable, Bernaudin, Myriam, Couteau, Florence, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

44. Interest of various radiothérapies to modulate glioblastoma inflammation

Author

Ferré, A.E., Leblond, M.M., Hélaine, Charly, Pérès, E.A., Edwige, Petit, Bernaudin, Myriam, Samuel, Valable, Couteau, Florence, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

45. Impact de stratégies nanoparticulaires de réoxygénation sur les macrophages associés aux glioblastomes

Author

Ferré, Aurélie, Anfray, Clement, Leblond, M.M., Ozcelik, H., Hélaine, Charly, Komaty, S, Edwige, Petit, Myriam, Bernaudin, Mintova, Svetlana, Samuel, Valable, Couteau, Florence, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire catalyse et spectrochimie (LCS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2019

46. ONCOModels/Cyceron facilities

Author

Samuel, Valable, Couteau, Florence, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2019

47. Carbogen-induced increases in tumor oxygenation depend on the vascular status of the tumor: A multiparametric MRI study in two rat glioblastoma models

Author

Edwige Petit, Aurélie N. Gérault, Laurent Chazaviel, Didier Divoux, Omar Touzani, Samuel Valable, Eric T. MacKenzie, Aurélien Corroyer-Dulmont, Ararat Chakhoyan, Jérôme Toutain, Myriam Bernaudin, Nicolas Delcroix, M.M. Leblond, F. Kauffmann, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unité Support CYCERON, Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques Nicolas Oresme (LMNO), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Vasodilation, 030218 nuclear medicine & medical imaging, Dynamic blood oxygenation level dependent, Rats, Nude, 03 medical and health sciences, 0302 clinical medicine, Carbogen, glioma, Glioma, Animals, Humans, Medicine, U87, Oxygen saturation (medicine), fractional cerebral blood volume, hypoxia, Brain Neoplasms, business.industry, Original Articles, Carbon Dioxide, Tumor Oxygenation, Hypoxia (medical), medicine.disease, Magnetic Resonance Imaging, Xenograft Model Antitumor Assays, Oxygen, Neurology, Cerebrovascular Circulation, Anesthesia, Neurology (clinical), medicine.symptom, Glioblastoma, Cardiology and Cardiovascular Medicine, business, tissue oxygen saturation, 030217 neurology & neurosurgery
Abstract

The alleviation of hypoxia in glioblastoma with carbogen to improve treatment has met with limited success. Our hypothesis is that the eventual benefits of carbogen depend on the capacity for vasodilation. We examined, with MRI, changes in fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent signals in response to carbogen. The analyses were performed in two xenograft models of glioma (U87 and U251) recognized to have different vascular patterns. Carbogen increased fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent signals in contralateral tissues. In the tumor core and peritumoral regions, changes were dependent on the capacity to vasodilate rather than on resting fractional cerebral blood volume. In the highly vascularised U87 tumor, carbogen induced a greater increase in fractional cerebral blood volume and blood oxygen saturation in comparison to the less vascularized U251 tumor. The blood oxygenation level dependent signal revealed a delayed response in U251 tumors relative to the contralateral tissue. Additionally, we highlight the considerable heterogeneity of fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent within U251 tumor in which multiple compartments co-exist (tumor core, rim and peritumoral regions). Finally, our study underlines the complexity of the flow/metabolism interactions in different models of glioblastoma. These irregularities should be taken into account in order to palliate intratumoral hypoxia in clinical trials.

Published
2016

48. Multimodal imaging based on MRI and PET reveals [18F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma

Author

Louisa Barré, Fanny Bouquet, Aurélie N. Gérault, Ariel Savina, Elodie A. Pérès, Aurélien Corroyer-Dulmont, Eric T. MacKenzie, Myriam Bernaudin, Didier Divoux, Edwige Petit, Jérôme Toutain, M Ibazizène, Samuel Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Roche SAS, 30, cours de l'Ile Seguin, 92650, Boulogne-Billancourt, France., Laboratoire Roche SAS [Boulogne Billancourt], Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Male, medicine.medical_specialty, Imaging biomarker, Bevacizumab, [SDV]Life Sciences [q-bio], Recurrent Glioma, Multimodal Imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Cell Line, Tumor, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Survival analysis, Fluorodeoxyglucose, Temozolomide, [ SDV ] Life Sciences [q-bio], medicine.diagnostic_test, Brain Neoplasms, Magnetic resonance imaging, General Medicine, Magnetic Resonance Imaging, Dideoxynucleosides, Rats, 3. Good health, PET, Treatment efficacy, Positron emission tomography, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Radiology, Radiopharmaceuticals, Glioblastoma, MRI, medicine.drug
Abstract

International audience; PURPOSE:The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme.METHODS:MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([(18)F]FDG and [(18)F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival.RESULTS:Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [(18)F]FLT uptake, cerebral blood volume and oedema. [(18)F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [(18)F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy.CONCLUSION:The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [(18)F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations.

Published
2015

49. Involvement of tumor microenvironment on the sensitivity of glioblastoma vascularization to irradiation

Author

Hélaine, Charly, Ferré, Aurélie, Leblond, M.M., Lambert, Gaelle, Didier, Divoux, Pérès, E.A., Myriam, Bernaudin, Samuel, Valable, Edwige, Petit, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; National audience

Published
2018

50. Effect of radio-induced products from glioblastoma cells on macrophages

Author

Ferré, Aurélie, Leblond, M.M., Hélaine, Charly, Pérès, E.A., Edwige, Petit, Myriam, Bernaudin, Samuel, Valable, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Couteau, Florence

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

CERVOXY; International audience

Published
2018

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