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1. A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome

Author

Ahuja, K., Vandenabeele, M., Nami, F., Lefevere, E., Van hoecke, J., Bergmans, S., Claes, M., Vervliet, T., Neyrinck, K., Burg, T., De Herdt, D., Bhaskar, P., Zhu, Y., Looser, Z. J., Loncke, J., Gsell, W., Plaas, M., Agostinis, P., Swinnen, J. V., Van Den Bosch, L., Bultynck, G., Saab, A. S., Wolfs, E., Chai, Y. C., Himmelreich, U., Verfaillie, C., Moons, L., and De Groef, L.

Published
2024
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2. Label-Free Iron Oxide Nanoparticles as Multimodal Contrast Agents in Cells Using Multi-Photon and Magnetic Resonance Imaging

Author

Reynders H, Van Zundert I, Silva R, Carlier B, Deschaume O, Bartic C, Rocha S, Basov S, Van Bael MJ, Himmelreich U, Verbiest T, and Zamora A

Subjects
iron oxide nanoparticles, photoluminescence, biomedical imaging, mri, cancer cells, multimodal imaging, Medicine (General), R5-920
Abstract

Hendrik Reynders,1 Indra Van Zundert,1 Rui Silva,1– 3 Bram Carlier,3 Olivier Deschaume,4 Carmen Bartic,4 Susana Rocha,1 Sergey Basov,5 Margriet J Van Bael,5 Uwe Himmelreich,3 Thierry Verbiest,1 Ana Zamora1,3 1Molecular Imaging and Photonics, KU Leuven, Leuven, Belgium; 2Engineering Department, Oporto University, Porto, Portugal; 3Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; 4Laboratory for Soft Matter and Biophysics, KU Leuven, Leuven, Belgium; 5Quantum Solid State Physics, KU Leuven, Leuven, BelgiumCorrespondence: Ana Zamora Email anamaria.zamoramartinez@kuleuven.beIntroduction: The inherent fluorescence properties of iron oxide nanoparticles (IONPs) were characterized, and their applicability for multiphoton imaging in cells was tested in combination with their magnetic resonance imaging (MRI) capabilities.Methods: Superparamagnetic iron oxide nanoparticles were synthesized and subsequently coated with polyethylene glycol to make them water-dispersible. Further characterization of the particles was performed using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and magnetic resonance relaxivity measurements. MRI and fluorescence properties of bare IONPs were first studied in solution and subsequently in A549-labeled cells.Results: The particles, with a core size of 11.3 ± 4.5 nm, showed a good negative MRI contrast in tissue-mimicking phantoms. In vitro studies in mammalian A549 cells demonstrate that these IONPs are biocompatible and can also produce significant T2/T2* contrast enhancement in IONPs-labeled cells. Furthermore, excitation-wavelength dependent photoluminescence was observed under one- and two-photon excitation.Discussion: The obtained results indicated that IONPs could be used for fluorescence label-free bioimaging at multiple wavelengths, which was proven by multiphoton imaging of IONPs internalization in A549 cancer cells.Keywords: iron oxide nanoparticles, photoluminescence, biomedical imaging, MRI, cancer cells, multimodal imaging

Published
2021

5. Targeting tumor cells and neovascularization using RGD-functionalized magnetoliposomes

Author

Garcia Ribeiro RS, Belderbos S, Danhier P, Gallo J, Manshian BB, Gallez B, Bañobre M, de Cuyper M, Soenen SJ, Gsell W, and Himmelreich U

Subjects
tumor targeting, SKOV-3, cRGD, magnetoliposomes, MRI, FLI, Medicine (General), R5-920
Abstract

Rita Sofia Garcia Ribeiro,1,* Sarah Belderbos,1,* Pierre Danhier,2 Juan Gallo,2 Bella B Manshian,1 Bernard Gallez,2 Manuel Bañobre,3 Marcel de Cuyper,4 Stefaan J Soenen,1 Willy Gsell,1 Uwe Himmelreich11Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Biomedical Sciences Group, Leuven B-3000, Belgium; 2Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Brussels B-1200, Belgium; 3Diagnostic Tools and Methods/Advanced (Magnetic) Theranostic Nanostructures Lab, International Iberian Nanotechnology Laboratory (INL), PT-Braga 4715-330, Portugal; 4Laboratory of Bionanocolloids, Interdisciplinary Research Centre, KULAK/KU Leuven, Kortrijk B-8500, Belgium*These authors contributed equally to this workPurpose: Magnetoliposomes (MLs) have shown great potential as magnetic resonance imaging contrast agents and as delivery vehicles for cancer therapy. Targeting the MLs towards the tumor cells or neovascularization could ensure delivery of drugs at the tumor site. In this study, we evaluated the potential of MLs targeting the αvβ3 integrin overexpressed on tumor neovascularization and different tumor cell types, including glioma and ovarian cancer.Methods: MLs functionalized with a Texas Red fluorophore (anionic MLs), and with the fluorophore and the cyclic Arginine-Glycine-Aspartate (cRGD; cRGD-MLs) targeting the αvβ3 integrin, were produced in-house. Swiss nude mice were subcutaneously injected with 107 human ovarian cancer SKOV-3 cells. Tumors were allowed to grow for 3 weeks before injection of anionic or cRGD-MLs. Biodistribution of MLs was followed up with a 7T preclinical magnetic resonance imaging (MRI) scanner and fluorescence imaging (FLI) right after injection, 2h, 4h, 24h and 48h post injection. Ex vivo intratumoral ML uptake was confirmed using FLI, electron paramagnetic resonance spectroscopy (EPR) and histology at different time points post injection.Results: In vivo, we visualized a higher uptake of cRGD-MLs in SKOV-3 xenografts compared to control, anionic MLs with both MRI and FLI. Highest ML uptake was seen after 4h using MRI, but only after 24h using FLI indicating the lower sensitivity of this technique. Furthermore, ex vivo EPR and FLI confirmed the highest tumoral ML uptake at 4 h. Last, a Perl’s stain supported the presence of our iron-based particles in SKOV-3 xenografts.Conclusion: Uptake of cRGD-MLs can be visualized using both MRI and FLI, even though the latter was less sensitive due to lower depth penetration. Furthermore, our results indicate that cRGD-MLs can be used to target SKOV-3 xenograft in Swiss nude mice. Therefore, the further development of this particles into theranostics would be of interest.Keywords: tumor targeting, SKOV-3, cRGD, magnetoliposomes, MRI, FLI

Published
2019

6. Radiation dose-escalation and dose-fractionation modulate the immune microenvironment, cancer stem cells and vasculature in experimental high-grade gliomas

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Riva, M., Wouters, R., Nittner, D., Ceusters, J., Sterpin, Edmond, Giovannoni, R., Himmelreich, U., Gsell, W., VAN Ranst, M., Coosemans, A., UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Riva, M., Wouters, R., Nittner, D., Ceusters, J., Sterpin, Edmond, Giovannoni, R., Himmelreich, U., Gsell, W., VAN Ranst, M., and Coosemans, A.

Published
2023

7. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

Author

D’Hollander A, Mathieu E, Jans H, Vande Velde G, Stakenborg T, Van Dorpe P, Himmelreich U, and Lagae L

Subjects
SERS - Gold Nanostars - Cancer Imaging, Medicine (General), R5-920
Abstract

Antoine D’Hollander,1–3 Evelien Mathieu,1,4 Hilde Jans,1 Greetje Vande Velde,2,3 Tim Stakenborg,1 Pol Van Dorpe,1,4 Uwe Himmelreich,2,3 Liesbet Lagae1,4 1Department of Life Science Technology, Imec, 2Department of Imaging and Pathology, Faculty of Medicine, Biomedical MRI Unit, 3Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC), 4Department of Physics, Faculty of Sciences, Laboratory of Solid State Physics and Magnetism, KU Leuven, Leuven, Belgium Abstract: The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. Keywords: SERS, gold nanostars, cancer imaging, Raman active

Published
2016

9. Variability in contrast agent uptake by different but similar stem cell types

Author

Ketkar-Atre A, Struys T, Soenen SJ, Lambrichts I, Verfaillie CM, De Cuyper M, and Himmelreich U

Subjects
Medicine (General), R5-920
Abstract

Ashwini Ketkar-Atre,1 Tom Struys,1,2 Stefaan J Soenen,3 Ivo Lambrichts,2 Catherine M Verfaillie,4 Marcel De Cuyper,5 Uwe Himmelreich1 1Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Biomedical Sciences Group, Katholieke Universiteit Leuven, Leuven, Belgium; 2Lab of Histology, Biomedical Research Institute, Hasselt University, Campus Diepenbeek, Agoralaan, Diepenbeek, Belgium; 3Lab for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium; 4Interdepartmental Stem Cell Institute, O&N IV, Katholieke Universiteit Leuven, Leuven, Belgium; 5Laboratory of BioNanoColloids, Interdisciplinary Research Centre, Katholieke Universiteit Leuven, Kortrijk, Belgium Abstract: The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies. Keywords: cell labeling, MR contrast agents, transmission electron microscopy, mesenchymal stem cells, multipotent adult progenitor cells, magnetic resonance imaging, nanoparticles, iron oxide

Published
2013

11. Phase-Change Perfluorobutane Polymerized Lipid-Shelled Nanodroplets for Ultrasound and MRI Imaging

Author

Toumia, Y, Heymans, S, Carlier, B, Saini, S, Lange, H, Dominici, F, Himmelreich, U, VAN DEN ABEELE, K, Sterpin, E, D'Hooge, J, D'Agostino, E, Paradossi, G, TOUMIA Y, HEYMANS S V, CARLIER B, SAINI S, LANGE H, DOMINICI F, HIMMELREICH U, VAN DEN ABEELE K, STERPIN E, D'HOOGE J, D'AGOSTINO E, PARADOSSI G, Toumia, Y, Heymans, S, Carlier, B, Saini, S, Lange, H, Dominici, F, Himmelreich, U, VAN DEN ABEELE, K, Sterpin, E, D'Hooge, J, D'Agostino, E, Paradossi, G, TOUMIA Y, HEYMANS S V, CARLIER B, SAINI S, LANGE H, DOMINICI F, HIMMELREICH U, VAN DEN ABEELE K, STERPIN E, D'HOOGE J, D'AGOSTINO E, and PARADOSSI G

Published
2019

13. Modulating ultrasound contrast generation from injectable nanodroplets for proton range verification by varying the degree of superheat

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Heymans, S.V., Carlier, B., Toumia, Y., Nooijens, S., Ingram, M., Giammanco, A., d’Agostino, E., Crijns, W., Bertrand, A., Paradossi, G., Himmelreich, U., D’hooge, J., Sterpin, Edmond, Van Den Abeele, K., UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Heymans, S.V., Carlier, B., Toumia, Y., Nooijens, S., Ingram, M., Giammanco, A., d’Agostino, E., Crijns, W., Bertrand, A., Paradossi, G., Himmelreich, U., D’hooge, J., Sterpin, Edmond, and Van Den Abeele, K.

Abstract

Purpose: Despite the physical benefits of protons over conventional photon radiation in cancer treatment, range uncertainties impede the ability to harness the full potential of proton therapy. While monitoring the proton range in vivo could reduce the currently adopted safety margins, a routinely applicable range verification technique is still lacking. Recently, phase-change nanodroplets were proposed for proton range verification, demonstrating a reproducible relationship between the proton range and generated ultrasound contrast after radiation-induced vaporization at 25°C. In this study, previous findings are extended with proton irradiations at different temperatures, including the physiological temperature of 37°C, for a novel nanodroplet formulation. Moreover, the potential to modulate the linear energy transfer (LET) threshold for vaporization by varying the degree of superheat is investigated, where the aim is to demonstrate vaporization of nanodroplets directly by primary protons. Methods: Perfluorobutane nanodroplets with a shell made of polyvinyl alcohol (PVA-PFB) or 10,12-pentacosadyinoic acid (PCDA-PFB) were dispersed in polyacrylamide hydrogels and irradiated with 62 MeV passively scattered protons at temperatures of 37°C and 50°C. Nanodroplet transition into echogenic microbubbles was assessed using ultrasound imaging (gray value and attenuation analysis) and optical images. The proton range was measured independently and compared to the generated contrast. Results: Nanodroplet design proved crucial to ensure thermal stability, as PVA-shelled nanodroplets dramatically outperformed their PCDA-shelled counterpart. At body temperature, a uniform radiation response proximal to the Bragg peak is attributed to nuclear reaction products interacting with PVA-PFB nanodroplets, with the 50% drop in ultrasound contrast being 0.17 mm ± 0.20 mm (mean ± standard deviation) in front of the proton range. Also at 50°C, highly reproducible ultrasound contrast profile

Published
2021

15. Phase-Change Perfluorobutane Polymerized Lipid-Shelled Nanodroplets for Ultrasound and MRI Imaging

Author

TOUMIA Y, HEYMANS S V, CARLIER B, SAINI S, LANGE H, DOMINICI F, HIMMELREICH U, VAN DEN ABEELE K, STERPIN E, D'HOOGE J, D'AGOSTINO E, PARADOSSI G, Toumia, Y, Heymans, S, Carlier, B, Saini, S, Lange, H, Dominici, F, Himmelreich, U, VAN DEN ABEELE, K, Sterpin, E, D'Hooge, J, D'Agostino, E, and Paradossi, G

Subjects
Phase-Change, polyperfluorobutane, nanodroplets, ultrasound, MRI
Published
2019

23. Establishment, characterization and imaging of a first platinum-resistant penile cancer patient derived xenograft in nude mice: An eUROGEN project

Author

Albersen, M., primary, Vanthoor, J., additional, Thomas, A., additional, Milenkovic, U., additional, Dumez, H., additional, De Meerleer, G., additional, Joniau, S., additional, Everaerts, W., additional, Tsaur, I., additional, Muneer, A., additional, Himmelreich, U., additional, Cawthorne, C., additional, Deroose, C.M., additional, Spans, L., additional, Vanden Bempt, I., additional, Leucci, E., additional, Van Rompuy, A., additional, and Rizzotto, L., additional

Published
2020
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36. Abstracts from the 4th ImmunoTherapy of Cancer Conference

Author

Ženka, J., primary, Caisová, V., additional, Uher, O., additional, Nedbalová, P., additional, Kvardová, K., additional, Masáková, K., additional, Krejčová, G., additional, Paďouková, L., additional, Jochmanová, I., additional, Wolf, K. I., additional, Chmelař, J., additional, Kopecký, J., additional, Loumagne, L., additional, Mestadier, J., additional, D’agostino, S., additional, Rohaut, A., additional, Ruffin, Y., additional, Croize, V., additional, Lemaître, O., additional, Sidhu, S. S., additional, Althammer, S., additional, Steele, K., additional, Rebelatto, M., additional, Tan, T., additional, Wiestler, T., additional, Spitzmueller, A., additional, Korn, R., additional, Schmidt, G., additional, Higgs, B., additional, Li, X., additional, Shi, L., additional, Jin, X., additional, Ranade, K., additional, Koeck, S., additional, Amann, A., additional, Gamerith, G., additional, Zwierzina, M., additional, Lorenz, E., additional, Zwierzina, H., additional, Kern, J., additional, Riva, M., additional, Baert, T., additional, Coosemans, A., additional, Giovannoni, R., additional, Radaelli, E., additional, Gsell, W., additional, Himmelreich, U., additional, Van Ranst, M., additional, Xing, F., additional, Qian, W., additional, Dong, C., additional, Xu, X., additional, Guo, S., additional, Shi, Q., additional, Quandt, D., additional, Seliger, B., additional, Plett, C., additional, Amberger, D. C., additional, Rabe, A., additional, Deen, D., additional, Stankova, Z., additional, Hirn, A., additional, Vokac, Y., additional, Werner, J., additional, Krämer, D., additional, Rank, A., additional, Schmid, C., additional, Schmetzer, H., additional, Guerin, M., additional, Weiss, J. M., additional, Regnier, F., additional, Renault, G., additional, Vimeux, L., additional, Peranzoni, E., additional, Feuillet, V., additional, Thoreau, M., additional, Guilbert, T., additional, Trautmann, A., additional, Bercovici, N., additional, Doraneh-Gard, F., additional, Boeck, C. L., additional, Gunsilius, C., additional, Kugler, C., additional, Schmohl, J., additional, Kraemer, D., additional, Ismann, B., additional, Schmetzer, H. M., additional, Markota, A., additional, Ochs, C., additional, May, P., additional, Gottschlich, A., additional, Gosálvez, J. Suárez, additional, Karches, C., additional, Wenk, D., additional, Endres, S., additional, Kobold, S., additional, Hilmenyuk, T., additional, Klar, R., additional, Jaschinski, F., additional, Augustin, F., additional, Manzl, C., additional, Hoflehner, E., additional, Moser, P., additional, Zelger, B., additional, Köck, S., additional, Schäfer, G., additional, Öfner, D., additional, Maier, H., additional, Sopper, S., additional, Prado-Garcia, H., additional, Romero-Garcia, S., additional, Sandoval-Martínez, R., additional, Puerto-Aquino, A., additional, Lopez-Gonzalez, J., additional, Rumbo-Nava, U., additional, Van Hoylandt, A., additional, Busschaert, P., additional, Vergote, I., additional, Laengle, J., additional, Pilatova, K., additional, Budinska, E., additional, Bencsikova, B., additional, Sefr, R., additional, Nenutil, R., additional, Brychtova, V., additional, Fedorova, L., additional, Hanakova, B., additional, Zdrazilova-Dubska, L., additional, Allen, Chris, additional, Ku, Yuan-Chieh, additional, Tom, Warren, additional, Sun, Yongming, additional, Pankov, Alex, additional, Looney, Tim, additional, Hyland, Fiona, additional, Au-Young, Janice, additional, Mongan, Ann, additional, Becker, A., additional, Tan, J. B. L., additional, Chen, A., additional, Lawson, K., additional, Lindsey, E., additional, Powers, J. P., additional, Walters, M., additional, Schindler, U., additional, Young, S., additional, Jaen, J. C., additional, Yin, S., additional, Chen, Y., additional, Gullo, I., additional, Gonçalves, G., additional, Pinto, M. L., additional, Athelogou, M., additional, Almeida, G., additional, Huss, R., additional, Oliveira, C., additional, Carneiro, F., additional, Merz, C., additional, Sykora, J., additional, Hermann, K., additional, Hussong, R., additional, Richards, D. M., additional, Fricke, H., additional, Hill, O., additional, Gieffers, C., additional, Pinho, M. P., additional, Barbuto, J. A. M., additional, McArdle, S. E., additional, Foulds, G., additional, Vadakekolathu, J. N., additional, Abdel-Fatah, T. M. A., additional, Johnson, C., additional, Hood, S., additional, Moseley, P., additional, Rees, R. C., additional, Chan, S. Y. T., additional, Pockley, A. G., additional, Rutella, S., additional, Geppert, C., additional, Hartmann, A., additional, Kumar, K. Senthil, additional, Gokilavani, M., additional, Wang, S., additional, Redondo-Müller, M., additional, Heinonen, K., additional, Marschall, V., additional, Thiemann, M., additional, Zhang, L., additional, Mao, B., additional, Jin, Y., additional, Zhai, G., additional, Li, Z., additional, Wang, Z., additional, An, X., additional, Qiao, M., additional, Zhang, J., additional, Weber, J., additional, Kluger, H., additional, Halaban, R., additional, Sznol, M., additional, Roder, H., additional, Roder, J., additional, Grigorieva, J., additional, Asmellash, S., additional, Meyer, K., additional, Steingrimsson, A., additional, Blackmon, S., additional, Sullivan, R., additional, Sutanto, W., additional, Guenther, T., additional, Schuster, F., additional, Salih, H., additional, Babor, F., additional, Borkhardt, A., additional, Kim, Y., additional, Oh, I., additional, Park, C., additional, Ahn, S., additional, Na, K., additional, Song, S., additional, Choi, Y., additional, Poprach, A., additional, Lakomy, R., additional, Selingerova, I., additional, Demlova, R., additional, Kozakova, S., additional, Valik, D., additional, Petrakova, K., additional, Vyzula, R., additional, Aguilar-Cazares, D., additional, Galicia-Velasco, M., additional, Camacho-Mendoza, C., additional, Islas-Vazquez, L., additional, Chavez-Dominguez, R., additional, Gonzalez-Gonzalez, C., additional, Lopez-Gonzalez, J. S., additional, Yang, S., additional, Moynihan, K. D., additional, Noh, M., additional, Bekdemir, A., additional, Stellacci, F., additional, Irvine, D. J., additional, Volz, B., additional, Kapp, K., additional, Oswald, D., additional, Wittig, B., additional, Schmidt, M., additional, Kleef, R., additional, Bohdjalian, A., additional, McKee, D., additional, Moss, R. W., additional, Saeed, Mesha, additional, Zalba, Sara, additional, Debets, Reno, additional, ten Hagen, Timo L. M., additional, Javed, S., additional, Becher, J., additional, Koch-Nolte, F., additional, Haag, F., additional, Gordon, E. M., additional, Sankhala, K. K., additional, Stumpf, N., additional, Tseng, W., additional, Chawla, S. P., additional, Suárez, N. González, additional, Báez, G. Bergado, additional, Rodríguez, M. Cruz, additional, Pérez, A. Gutierrez, additional, García, L. Chao, additional, Fernández, D. Hernández, additional, Pous, J. Raymond, additional, Ramírez, B. Sánchez, additional, Jacoberger-Foissac, C., additional, Saliba, H., additional, Seguin, C., additional, Brion, A., additional, Frisch, B., additional, Fournel, S., additional, Heurtault, B., additional, Otterhaug, T., additional, Håkerud, M., additional, Nedberg, A., additional, Edwards, V., additional, Selbo, P., additional, Høgset, A., additional, Jaitly, T., additional, Dörrie, J., additional, Schaft, N., additional, Gross, S., additional, Schuler-Thurner, B., additional, Gupta, S., additional, Taher, L., additional, Schuler, G., additional, Vera, J., additional, Rataj, F., additional, Kraus, F., additional, Grassmann, S., additional, Chaloupka, M., additional, Lesch, S., additional, Heise, C., additional, Cadilha, B. M. Loureiro, additional, and Dorman, K., additional

Published
2017
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37. Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia

Author

Russo, F, Toelen, J, Eastwood, M, Jimenez, J, Miyague, A, Vande Velde, G, Dekoninck, P, Himmelreich, U, Vergani, P, Allegaert, K, Deprest, J, RUSSO, FRANCESCA MARIA, VERGANI, PATRIZIA, Deprest, J., Russo, F, Toelen, J, Eastwood, M, Jimenez, J, Miyague, A, Vande Velde, G, Dekoninck, P, Himmelreich, U, Vergani, P, Allegaert, K, Deprest, J, RUSSO, FRANCESCA MARIA, VERGANI, PATRIZIA, and Deprest, J.

Abstract

Introduction The management of congenital diaphragmatic hernia (DH) would benefit from an antenatal medical therapy, which addresses both lung hypoplasia and persistent pulmonary hypertension. We aimed at evaluating the pulmonary effects of sildenafil in the fetal rabbit model for DH. Methods We performed a dose-finding study to achieve therapeutic fetal plasmatic concentrations without toxicity following maternal sildenafil administration. Subsequently, DH fetuses were randomly exposed to transplacental placebo or sildenafil 10 mg/kg/day from gestational day 24 until examination at term (day 30). Efficacy measures were ipsilateral pulmonary vascular and airway morphometry, micro-CT-based branching analysis, Doppler flow in the main pulmonary artery and postnatal lung mechanics. Results Fetal sildenafil plasmatic concentration was above the minimal therapeutic level for at least 22 h/day without maternal and fetal side effects. The placeboexposed DH fetuses had increased wall thickness in peripheral pulmonary vessels and significantly less fifth-order vessels compared with controls (CTR). Sildenafil-exposed DH fetuses, instead, had a medial and adventitial thickness in peripheral pulmonary vessels in the normal range and normal vascular branching. Fetal pulmonary artery Doppler showed a reduction of pulmonary vascular resistances both in DH and in CTR fetuses treated by sildenafil compared with the placebotreated ones. Sildenafil also reversed the mean terminal bronchiolar density to normal and improved lung mechanics, yet without measurable impact on lung-to-bodyweight ratio. Conclusions In the rabbit model for DH, antenatal sildenafil rescues vascular branching and architecture, reduces pulmonary vascular resistances and also improves airway morphometry and respiratory mechanics.

Published
2016

45. P187 MRI T2 relaxometry to image fibrosis in patients with Crohn's disease

Author

Breynaert, C., primary, Dresselaers, T., additional, Peeters, R., additional, Roebben, I., additional, Van Steen, K., additional, Vanuytsel, T., additional, Ballet, V., additional, Ferrante, M., additional, Vermeire, S., additional, Rutgeerts, P., additional, Himmelreich, U., additional, Dymarkowski, S., additional, Vanbeckevoort, D., additional, and Van Assche, G., additional

Published
2014
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49. 19F-heptuloses as tools for the non-invasive imaging of GLUT-2 expressing cells

Author

Malaisse, Willy, Zhang, Y., Louchami, Karim, Sharma, Sandhya, Dresselaers, Tom, Himmelreich, U, Novotny, G.W., Mandrup-Poulsen, T., Waschke, D, Leshch, Y, Thimm, J, Thiem, J, Sener, Abdullah, Malaisse, Willy, Zhang, Y., Louchami, Karim, Sharma, Sandhya, Dresselaers, Tom, Himmelreich, U, Novotny, G.W., Mandrup-Poulsen, T., Waschke, D, Leshch, Y, Thimm, J, Thiem, J, and Sener, Abdullah

Abstract

Suitable analogs of d-mannoheptulose are currently considered as possible tools for the non-invasive imaging of pancreatic islet insulin-producing cells. Here, we examined whether 19F-heptuloses could be used for non-invasive imaging of GLUT2-expressing cells. After 20 min incubation, the uptake of 19F-heptuloses (25 mM) by rat hepatocytes, as assessed by 19F NMR spectroscopy, ranged from 0.50 (1-deoxy-1-fluoro-d- mannoheptulose and 3-deoxy-3-fluoro-d-mannoheptulose) to 0.25 (1,3-dideoxy-1,3-difluoro-d-mannoheptulose) and 0.13 (1-deoxy-1-fluoro-d- glucoheptulose, 3-deoxy-3-fluoro-d-glucoheptulose and 1,3-dideoxy-1,3-difluoro- d-glucoheptulose) μmol per 3 × 10 6 cells. 19F MRI experiments also allowed the detection of 1-deoxy-1-fluoro-d-mannoheptulose in rat hepatocytes. All three 19F-mannoheptuloses cited above, as well as 7-deoxy-7-fluoro-d-mannoheptulose and 1-deoxy-1-fluoro-d-glucoheptulose inhibited insulin release evoked in rat isolated pancreatic islets by 10 mM d-glucose to the same extent as that observed with an equivalent concentration (10 mM) of d-mannoheptulose, while 3-deoxy-3-fluoro-d-glucoheptulose and 1,3-dideoxy-1,3-difluoro-d-glucoheptulose (also 10 mM) were less potent than d-mannoheptulose in inhibiting insulin release. The 1-deoxy-1-fluoro-d- mannoheptulose and 3-deoxy-3-fluoro-d-mannoheptulose only marginally affected INS-1 cell viability. These findings are compatible with the view that selected 19F-heptuloses may represent suitable tools for the non-invasive imaging of hepatocytes and insulin-producing cells by 19F MRI. © 2011 Elsevier Inc. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2012

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