Assessment of a7 nicotinic @entity934 receptor availability in juvenile XXXX brain with [     F]NS10743.

@entity1707 @entity72718 @entity11702 @entity5161 @entity28900 @entity72717 @entity934
PURPOSE: To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile @entity1707 for @entity72717 , a novel @entity72718 derivative targeting a7 nicotinic @entity934 receptors (a7 nAChRs). METHODS: Dynamic PET recordings were made in @entity5161 -anaesthetized juvenile @entity1707 during 120 min after administration of @entity72717 under baseline conditions (n = 3) and after blocking of the a7 nAChR with @entity28900 (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 @entity72717 passed readily into the brain, with peak uptake occurring in a7 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 @entity28900 significantly decreased @entity72717 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( @entity11702 ). The baseline BP( @entity11702 ) ranged from 0.39    0.08 in the cerebellum to 0.76    0.07 in the temporal lobe. Pretreatment and constant infusion with @entity28900 significantly reduced the BP( @entity11702 ) in regions with high @entity72717 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP( @entity11702 ) in low binding regions (cerebellum: -16%, p = 0.2). CONCLUSION: This study confirms the potential of @entity72717 as a target-specific radiotracer for the molecular imaging of central a7 nAChRs by PET.
