title: Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation.
abstract: BACKGROUND
  The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [(18)F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics.
  
  
  METHODS
  Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [(18)F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time-activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values.
  
  
  RESULTS
  The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [(18)F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5-30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys.
  
  
  CONCLUSIONS
  This initial study in humans shows that [(18)F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [(18)F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.
authors.affiliation: Université François Rabelais de Tours, UMR-S930 and CNRS ERL 3106, Tours, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Arlicot
authors.forename: Johnny
authors.initials: J
authors.lastname: Vercouillie
authors.forename: Maria-João
authors.initials: MJ
authors.lastname: Ribeiro
authors.forename: Clovis
authors.initials: C
authors.lastname: Tauber
authors.forename: Yann
authors.initials: Y
authors.lastname: Venel
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Baulieu
authors.forename: Serge
authors.initials: S
authors.lastname: Maia
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stabin
authors.forename: Aaron
authors.initials: A
authors.lastname: Reynolds
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006262:Health; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000378:metabolism / Q000493:pharmacokinetics*; D011874:Radiometry; D018079:Receptors, GABA / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005462:Fluorine Radioisotopes; 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; C499229:TSPO protein, human