title: Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [¹⁸F]NS10743.
abstract: OBJECTIVE
  To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [(18)F]NS10743, a novel diazabicyclononane derivative targeting α7 nicotinic acetylcholine receptors (α7 nAChRs).
  
  
  METHODS
  Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [(18)F]NS10743 under baseline conditions (n = 3) and after blocking of the α7 nAChR with NS6740 (3 mg·kg(-1) bolus + 1 mg·kg(-1)·h(-1) continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input.
  
  
  RESULTS
  Plasma [(18)F]NS10743 passed readily into the brain, with peak uptake occurring in α7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUV(max) was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUV(max) 1.53 ± 0.32). Administration of NS6740 significantly decreased [(18)F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BP(ND). The baseline BP(ND) ranged from 0.39 ± 0.08 in the cerebellum to 0.76 ± 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BP(ND) in regions with high [(18)F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP(ND) in low binding regions (cerebellum: -16%, p = 0.2).
  
  
  CONCLUSIONS
  This study confirms the potential of [(18)F]NS10743 as a target-specific radiotracer for the molecular imaging of central α7 nAChRs by PET.
authors.affiliation: Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany. w.deuther-conrad@hzdr.de
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Achim
authors.initials: A
authors.lastname: Hiller
authors.forename: Georg
authors.initials: G
authors.lastname: Becker
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.forename: Uta
authors.initials: U
authors.lastname: Funke
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.forename: Dan
authors.initials: D
authors.lastname: Peters
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology; D053961:Azabicyclo Compounds / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D018722:Nicotinic Agonists / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001372:Aza Compounds; D053961:Azabicyclo Compounds; C562060:NS 10743; D018722:Nicotinic Agonists; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor