title: In vivo imaging and characterization of [(18)F]DPA-714, a potential new TSPO ligand, in mouse brain and peripheral tissues using small-animal PET.
abstract: BACKGROUND
  The translocator protein 18 kDa (TSPO), a biochemical marker of neuroinflammation, is highly expressed in the brain activated microglia and it is also expressed by peripheral inflammatory cells and normal peripheral tissues. Thus, development of radioligands for the TSPO may contribute to further understanding the in vivo TSPO function in central and peripheral inflammatory processes and other pathologies. Here, we report the biodistribution, the specific binding and the radiometabolites of [(18)F]DPA-714, a promising fluorinated PET radiotracer, in normal mice using a microPET/CT scanner.
  
  
  METHODS
  The in vivo biodistribution and kinetics of [(18)F]DPA-714 were measured in mice brain and peripheral tissues. Specific binding to TSPO sites was assessed using pharmacological competitive studies by means of saturation experiments performed by i.v. injection of 1mg/kg of unlabeled DPA-714 or 3mg/kg of unlabeled PK11195. A region of interest analysis was performed to generate time-activity curves in the brain, heart, lung, kidney, spleen and liver. Metabolites assay was performed in the plasma and peripheral organs by radio-HPLC.
  
  
  RESULTS
  [(18)F]DPA-714 reached high concentration in lung, heart, kidney and spleen, tissues well known to be rich in TSPO sites. [(18)F]DPA-714 kinetics were faster in the lung and slower in the kidney. Pre-injection of unlabeled DPA-714 or PK11195 inhibited about 80% of [(18)F]DPA-714 uptake in the lung and heart (p<0.0005). The percentage of inhibition in the kidney was lower and achieved at later times only with DPA-714 (p<0.05) but not with PK11195. Sixty minutes after radiotracer injection only unmetabolized radioligand was found in the brain, lung, heart and spleen.
  
  
  CONCLUSIONS
  These results suggest that [(18)F]DPA-714 is a suitable PET ligand for imaging in mice brain and peripheral tissues since it binds with high specificity TSPO binding sites and it is almost unchanged at 60 minutes after radiotracer injection in the brain and TSPO-rich regions.
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vicidomini
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Panico
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Greco
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gargiulo
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Anna Rita Daniela
authors.initials: AR
authors.lastname: Coda
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zannetti
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Gramanzini
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy.
authors.forename: Giovanni N
authors.initials: GN
authors.lastname: Roviello
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Quarantelli
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Alfano
authors.affiliation: Inserm U970, PARCC, Université Paris Descartes, Hôpital Européen Georges Pompidou, Paris, France; CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.affiliation: CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Dollé
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; CEINGE, Biotecnologie Avanzate, s.c.a.r.l., Naples, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Brunetti
authors.affiliation: Institute of Biostructure and Bioimaging, CNR, Naples, Italy. Electronic address: sabina.pappata@ibb.cnr.it.
authors.forename: Sabina
authors.initials: S
authors.lastname: Pappatà
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: C463819:Bzrp protein, mouse; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D008024:Ligands; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C037850:PK 11195
keywords: Biodistribution; Microglia; Neuroinflammation; PET; TSPO; [(18)F]DPA-714