PURPOSE: The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [(18)F]PBR111 in a rodent model of acute inflammation and compare it with [(11)C]CLINME, an (11)C-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [(11)C]PK11195. METHODS: We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. RESULTS: We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [(18)F]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [(18)F]PBR111 administration, induces a rapid and complete displacement of [(18)F]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [(11)C]PK11195. CONCLUSION: [(18)F]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of (18)F over (11)C, these results support [(18)F]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging.
PURPOSE: The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [(18)F]PBR111 in a rodent model of acute inflammation and compare it with [(11)C]CLINME, an (11)C-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [(11)C]PK11195. METHODS: We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. RESULTS: We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [(18)F]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [(18)F]PBR111 administration, induces a rapid and complete displacement of [(18)F]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [(11)C]PK11195. CONCLUSION: [(18)F]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of (18)F over (11)C, these results support [(18)F]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging.
Authors: Petra Schweinhardt; Peter Fransson; Lars Olson; Christian Spenger; Jesper L R Andersson Journal: J Neurosci Methods Date: 2003-10-30 Impact factor: 2.390
Authors: Alan A Wilson; Armando Garcia; Jun Parkes; Patrick McCormick; Karin A Stephenson; Sylvain Houle; Neil Vasdev Journal: Nucl Med Biol Date: 2008-04 Impact factor: 2.408
Authors: Emmanuelle Briard; Sami S Zoghbi; Masao Imaizumi; Jonathan P Gourley; H Umesha Shetty; Jinsoo Hong; Vanessa Cropley; Masahiro Fujita; Robert B Innis; Victor W Pike Journal: J Med Chem Date: 2007-12-08 Impact factor: 7.446
Authors: Christopher J R Fookes; Tien Q Pham; Filomena Mattner; Ivan Greguric; Christian Loc'h; Xiang Liu; Paula Berghofer; Rachael Shepherd; Marie-Claude Gregoire; Andrew Katsifis Journal: J Med Chem Date: 2008-06-17 Impact factor: 7.446
Authors: Federico E Turkheimer; Paul Edison; Nicola Pavese; Federico Roncaroli; Alexander N Anderson; Alexander Hammers; Alexander Gerhard; Rainer Hinz; Yan F Tai; David J Brooks Journal: J Nucl Med Date: 2007-01 Impact factor: 10.057
Authors: Lisa M Kosloski; Duy M Ha; Jessica A L Hutter; David K Stone; Michael R Pichler; Ashley D Reynolds; Howard E Gendelman; R Lee Mosley Journal: J Neurochem Date: 2010-05-26 Impact factor: 5.372
Authors: Frederick M Lartey; G-One Ahn; Bin Shen; Keith-Travis Cord; Tenille Smith; Joshua Y Chua; Sahar Rosenblum; Hongguang Liu; Michelle L James; Sophia Chernikova; Star W Lee; Laura J Pisani; Rabindra Tirouvanziam; John W Chen; Theo D Palmer; Frederick T Chin; Raphael Guzman; Edward E Graves; Billy W Loo Journal: Mol Imaging Biol Date: 2013-07-09 Impact factor: 3.488
Authors: Catherine A Foss; Djahida Bedja; Ronnie C Mease; Haofan Wang; David A Kass; Subroto Chatterjee; Martin G Pomper Journal: Biochem Biophys Res Commun Date: 2015-04-06 Impact factor: 3.575
Authors: Mike E Robbins; Judy K Brunso-Bechtold; Ann M Peiffer; Christina I Tsien; Janet E Bailey; Lawrence B Marks Journal: Radiat Res Date: 2012-02-21 Impact factor: 2.841
Authors: P D Callaghan; C A Wimberley; G L Rahardjo; P J Berghofer; T Q Pham; T Jackson; D Zahra; T Bourdier; N Wyatt; I Greguric; N R Howell; R Siegele; Z Pastuovic; F Mattner; C Loc'h; M C Gregoire; A Katsifis Journal: Eur J Nucl Med Mol Imaging Date: 2014-09-18 Impact factor: 9.236
Authors: Brad A Hobson; Douglas J Rowland; Sílvia Sisó; Michelle A Guignet; Zachary T Harmany; Suren B Bandara; Naomi Saito; Danielle J Harvey; Donald A Bruun; Joel R Garbow; Abhijit J Chaudhari; Pamela J Lein Journal: Toxicol Sci Date: 2019-08-01 Impact factor: 4.849
Authors: S Eberl; A Katsifis; M A Peyronneau; L Wen; D Henderson; C Loc'h; I Greguric; J Verschuer; T Pham; P Lam; F Mattner; A Mohamed; M J Fulham Journal: Eur J Nucl Med Mol Imaging Date: 2016-10-04 Impact factor: 9.236
Authors: William C Kreisl; Kimberly J Jenko; Christina S Hines; Chul Hyoung Lyoo; Winston Corona; Cheryl L Morse; Sami S Zoghbi; Thomas Hyde; Joel E Kleinman; Victor W Pike; Francis J McMahon; Robert B Innis Journal: J Cereb Blood Flow Metab Date: 2012-09-12 Impact factor: 6.200