title: In vivo evaluation of [(123)I]MNI-420: a novel single photon emission computed tomography radiotracer for imaging of adenosine 2A receptors in brain.
abstract: BACKGROUND
  Dysregulation of adenosine 2A (A2A) receptor function in brain has been implicated in multiple psychiatric and neurodegenerative disorders, including schizophrenia and Parkinson's disease, making the development of an imaging agent to study A2A receptors in both healthy brain and disease states desirable. In this study, [(123)I]MNI-420 was evaluated as a potential single photon emission computed tomography (SPECT) radiotracer for imaging A2A receptors in brain.
  
  
  METHODS
  Two adult male monkeys (Macaca fascicularis) and three adult female baboons (Papio anubis) were anesthetized and imaged on Neurofocus SPECT cameras. Baboons underwent baseline and displacement studies using varying doses of caffeine (2.0-20mg/kg). Baseline and pre-blocking experiments with multiple doses of preladenant (0.01-1.2mg/kg), a highly selective A2A antagonist, were performed in cynomolgus monkeys.
  
  
  RESULTS
  Following bolus intravenous (i.v.) injection, [(123)I]MNI-420 rapidly entered the non-human primate brain. The regional brain accumulation of [(123)I]MNI-420 matched the known distribution of A2A receptors in brain (highest in the striatum). Striatum to cerebellum ratios and binding potentials of around 3.0-3.5 and 2.0-2.5, respectively, were measured in monkey and baboon brain. A dose-dependent occupancy was observed following i.v. injection of caffeine at pseudo-equilibrium conditions during displacement experiments. Pre-treatment with preladenant blocked specific binding in A2A rich regions in a dose-dependent fashion.
  
  
  CONCLUSIONS
  The data indicate that [(123)I]MNI-420 holds promise as a SPECT radiotracer for imaging A2A receptors in brain and further evaluation is warranted, in order to determine its utility as a SPECT radiotracer for imaging of A2A in brain.
authors: Molecular NeuroImaging, LLC, New Haven, USA. atavares@mnimaging.com
authors: Adriana Alexandre Dos Santos
authors: AA
authors: Tavares
authors: Jeffery
authors: J
authors: Batis
authors: Olivier
authors: O
authors: Barret
authors: David
authors: D
authors: Alagille
authors: Christine
authors: C
authors: Vala
authors: Greg
authors: G
authors: Kudej
authors: Andrei
authors: A
authors: Koren
authors: Kelly P
authors: KP
authors: Cosgrove
authors: Katie
authors: K
authors: Nice
authors: Jeffrey H
authors: JH
authors: Kordower
authors: John
authors: J
authors: Seibyl
authors: Gilles D
authors: GD
authors: Tamagnan
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring; D008252:Macaca fascicularis; D008297:Male; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles; D011849:Radioactive Tracers; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
chemical_list: C583370:7-(2-(4-(2-fluoro-4-iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidin-5-amine; D006575:Heterocyclic Compounds, 3-Ring; D011720:Pyrazoles; D011849:Radioactive Tracers; D043705:Receptor, Adenosine A2A