caa a22 4500 445314303 CHVBK 20180317142641.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11095-011-0552-0 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0552-0 New Fluorescent Probes Targeting the Mitochondrial-Located Translocator Protein 18kDa (TSPO) as Activated Microglia Imaging Agents [Elektronische Daten] [Nunzio Denora, Valentino Laquintana, Adriana Trapani, Hiromi Suzuki, Makoto Sawada, Giuseppe Trapani] ABSTRACT: Purpose: To evaluate the utility of new Translocator protein 18kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia. Methods: Compounds 2-4 were synthesized; their stability and affinity for TSPO were determined. Compounds 2-4 were incubated both with Ra2 cells in the presence of LPS, a potent activator of microglia, and with tissue sections of normal and chemically injured brains. Compounds 2-4 were injected into carotid artery or directly in striatum of mice. Cells and tissue sections from these in vitro and in vivo studies were observed by fluorescence microscopy after histochemical treatments. Results: Compounds 2-4 are stable in both buffer and physiological medium and showed high affinity for TSPO and were found to stain live Ra2 microglial cells effectively. Double staining with Mito Tracker Red suggested that binding sites of compounds 2 and 3 may exist on mitochondria. In vivo studies showed that compounds 2-4 may penetrate in part into brain; moreover, cells in mouse striatum were stained with compounds 2-4 and microglial marker CD11b. Conclusion: Compounds 2-4 can fluorescently label activated microglia in vitro and in vivo. Springer Science+Business Media, LLC, 2011 activated microglia imaging nationallicence fluorescence microscopy nationallicence imidazopyridine-compounds nationallicence TSPO nationallicence FITC : fluorescein isothiocyanate isomer 1 nationallicence LPS : lipopolysaccharide nationallicence PBR : peripheral benzodiazepine receptor nationallicence PET : positron emission tomography nationallicence RBITC : rhodamine B isothiocyanate nationallicence TSPO : translocator protein 18kDa nationallicence Denora Nunzio Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut Laquintana Valentino Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut Trapani Adriana Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut Suzuki Hiromi Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, 464-8601, Nagoya, Japan aut Sawada Makoto Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, 464-8601, Nagoya, Japan aut Trapani Giuseppe Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2820-2832 0724-8741 28:11<2820 2011 28 11095 https://doi.org/10.1007/s11095-011-0552-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0552-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Denora Nunzio Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Laquintana Valentino Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Trapani Adriana Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut NATIONALLICENCE 700 1- Suzuki Hiromi Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, 464-8601, Nagoya, Japan aut NATIONALLICENCE 700 1- Sawada Makoto Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, 464-8601, Nagoya, Japan aut NATIONALLICENCE 700 1- Trapani Giuseppe Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125, Bari, Italy aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/11(2011-11-01), 2820-2832 0724-8741 28:11<2820 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer