title: Characterization in humans of 18F-MNI-444, a PET radiotracer for brain adenosine 2A receptors.
abstract: PET with selective adenosine 2A receptor (A2A) radiotracers can be used to study a variety of neurodegenerative and neuropsychiatric disorders in vivo and to support drug-discovery studies targeting A2A. The aim of this study was to describe the first in vivo evaluation of (18)F-MNI-444, a novel PET radiotracer for imaging A2A, in healthy human subjects.
  
  
  METHODS
  Ten healthy human volunteers were enrolled in this study; 6 completed the brain PET studies and 4 participated in the whole-body PET studies. Arterial blood was collected for invasive kinetic modeling of the brain PET data. Noninvasive methods of data quantification were also explored. Test-retest reproducibility was evaluated in 5 subjects. Radiotracer distribution and dosimetry was determined using serial whole-body PET images acquired over 6 h post-radiotracer injection. Urine samples were collected to calculate urinary excretion.
  
  
  RESULTS
  After intravenous bolus injection, (18)F-MNI-444 rapidly entered the brain and displayed a distribution consistent with known A2A densities in the brain. Binding potentials ranging from 2.6 to 4.9 were measured in A2A-rich regions, with an average test-retest variability of less than 10%. The estimated whole-body radiation effective dose was approximately 0.023 mSv/MBq.
  
  
  CONCLUSIONS
  (18)F-MNI-444 is a useful PET radiotracer for imaging A2A in the human brain. The superior in vivo brain kinetic properties of (18)F-MNI-444, compared with previously developed A2A radiotracers, provide the opportunity to foster global use of in vivo A2A PET imaging in neuroscience research.
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and obarret@mnimaging.com.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barret
authors.affiliation: UCB Pharma SPRL, Braine-l'Alleud, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: Christine
authors.initials: C
authors.lastname: Vala
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: Adriana
authors.initials: A
authors.lastname: Tavares
authors.affiliation: UCB Pharma SPRL, Braine-l'Alleud, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: Danna
authors.initials: D
authors.lastname: Jennings
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: Ken
authors.initials: K
authors.lastname: Marek
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: David
authors.initials: D
authors.lastname: Russell
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: Molecular NeuroImaging, LLC, New Haven, Connecticut; and.
authors.forename: Gilles
authors.initials: G
authors.lastname: Tamagnan
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping / Q000379:methods; D005260:Female; D005462:Fluorine Radioisotopes; D064368:Healthy Volunteers; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011786:Quality Control; D011874:Radiometry; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A / Q000737:chemistry*; D015203:Reproducibility of Results; D051598:Whole Body Imaging; D055815:Young Adult
chemical_list: D005462:Fluorine Radioisotopes; D006575:Heterocyclic Compounds, 3-Ring; C000598565:MNI-444; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A
keywords: 18F-MNI-444; A2A receptors; PET; dosimetry; kinetic modeling