title: In vivo imaging of neuroinflammation: a comparative study between [(18)F]PBR111, [ (11)C]CLINME and [ (11)C]PK11195 in an acute rodent model.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  [(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.affiliation: CEA, I2BM, SHFJ, Laboratoire d'Imagerie Moléculaire Expérimentale (LIME), 4 place Leclerc, 91400 Orsay, France.
authors.forename: Nadja
authors.initials: N
authors.lastname: Van Camp
authors.forename: Raphael
authors.initials: R
authors.lastname: Boisgard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Kuhnast
authors.forename: Benoit
authors.initials: B
authors.lastname: Thézé
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Grégoire
authors.forename: Fabien
authors.initials: F
authors.lastname: Chauveau
authors.forename: Hervé
authors.initials: H
authors.lastname: Boutin
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
mesh_terms: D000081:Acetamides / Q000378:metabolism; D000577:Amides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism; D008024:Ligands; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; C550561:2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide; C525077:2-(6-chloro-2-(4-iodophenyl)-imidazo(1,2-alpha)pyridin-3-yl)-N-ethyl-N-methyl-acetamide; D000081:Acetamides; D000577:Amides; D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D008024:Ligands; D011725:Pyridines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat