Specific Imaging of Inflammation with the 18kDa Translocator Protein Ligand DPA-714 in Animal Models of Epilepsy and Stroke

作者: Denise Harhausen , Violetta Sudmann , Uldus Khojasteh , Jochen Müller , Marietta Zille

DOI: 10.1371/JOURNAL.PONE.0069529

关键词: LesionInflammationKainic acidPathologyBlood–brain barrierEpilepsyDPA-714MicrogliaTranslocator proteinPharmacologyChemistryGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

摘要: Inflammation is a pathophysiological hallmark of many diseases the brain. Specific imaging cells and molecules that contribute to cerebral inflammation therefore highly desirable, both for research in clinical application. The 18 kDa translocator protein (TSPO) has been established as suitable target detection activated microglia/macrophages. A number novel TSPO ligands have developed recently. Here, we evaluated high affinity ligand DPA-714 marker brain two independent animal models. For first time, specificity radiolabeled microglia/macrophages was studied rat model epilepsy (induced using Kainic acid) mouse stroke (transient middle artery occlusion, tMCAO) high-resolution autoradiography immunohistochemistry. Additionally, cold-compound blocking experiments were performed changes blood-brain barrier (BBB) permeability determined. Target-to-background ratios 2 3 achieved lesioned vs. unaffected tissue tMCAO models, respectively. In uptake into lesion corresponded well with extent Ox42- or Iba1-immunoreactive model, almost completely blocked by pre-injection FEDAA1106, another high-affinity ligand. Ligand degree BBB opening size model. We provide further strong evidence specific image experimental models inflammation.

参考文章(35)
Jennifer L. Hellier, F. Edward Dudek, Chemoconvulsant model of chronic spontaneous seizures. Current protocols in protein science. ,vol. 31, ,(2005) , 10.1002/0471142301.NS0919S31
Hervé Boutin, Fabien Chauveau, Cyrille Thominiaux, Bertrand Kuhnast, Marie-Claude Grégoire, Sébastien Jan, Régine Trebossen, Frédéric Dollé, Bertrand Tavitian, Filomena Mattner, Andrew Katsifis, In vivo imaging of brain lesions with [(11)C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors. Glia. ,vol. 55, pp. 1459- 1468 ,(2007) , 10.1002/GLIA.20562
Abraham Martín, Raphaël Boisgard, Benoit Thézé, Nadja Van Camp, Bertrand Kuhnast, Annelaure Damont, Michael Kassiou, Frédéric Dollé, Bertrand Tavitian, Evaluation of the PBR/TSPO Radioligand [18F]DPA-714 in a Rat Model of Focal Cerebral Ischemia Journal of Cerebral Blood Flow and Metabolism. ,vol. 30, pp. 230- 241 ,(2010) , 10.1038/JCBFM.2009.205
A. Wunder, J. Klohs, U. Dirnagl, Non-invasive visualization of CNS inflammation with nuclear and optical imaging. Neuroscience. ,vol. 158, pp. 1161- 1173 ,(2009) , 10.1016/J.NEUROSCIENCE.2008.10.005
M. Cosenza-Nashat, M.-L. Zhao, H.-S. Suh, J. Morgan, R. Natividad, S. Morgello, S. C. Lee, Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathology and Applied Neurobiology. ,vol. 35, pp. 306- 328 ,(2009) , 10.1111/J.1365-2990.2008.01006.X
Annachiara Cagnin, Michael Kassiou, Steve R. Meikle, Richard B. Banati, Positron emission tomography imaging of neuroinflammation. Neurotherapeutics. ,vol. 4, pp. 443- 452 ,(2007) , 10.1016/J.NURT.2007.04.006
Alexandra Winkeler, Raphael Boisgard, Ali R. Awde, Albertine Dubois, Benoit Thézé, Jinzi Zheng, Luisa Ciobanu, Frédéric Dollé, Thomas Viel, Andreas H. Jacobs, Bertrand Tavitian, The translocator protein ligand [18F]DPA-714 images glioma and activated microglia in vivo European Journal of Nuclear Medicine and Molecular Imaging. ,vol. 39, pp. 811- 823 ,(2012) , 10.1007/S00259-011-2041-4
Annamaria Vezzani, Alon Friedman, Raymond J. Dingledine, The role of inflammation in epileptogenesis Neuropharmacology. ,vol. 69, pp. 16- 24 ,(2013) , 10.1016/J.NEUROPHARM.2012.04.004
Sriram Venneti, Brian J. Lopresti, Clayton A. Wiley, Molecular imaging of microglia/macrophages in the brain. Glia. ,vol. 61, pp. 10- 23 ,(2013) , 10.1002/GLIA.22357
G. Abourbeh, B. Theze, R. Maroy, A. Dubois, V. Brulon, Y. Fontyn, F. Dolle, B. Tavitian, R. Boisgard, Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18 kDa Translocator Protein Radioligand [18F]DPA-714 The Journal of Neuroscience. ,vol. 32, pp. 5728- 5736 ,(2012) , 10.1523/JNEUROSCI.2900-11.2012