Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [18F]NS10743

To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [F-18]NS10743, a novel diazabicyclononane derivative targeting alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChRs). Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [F-18]NS10743 under baseline conditions (n = 3) and after blocking of the alpha 7 nAChR with NS6740 (3 mg center dot kg(-1) bolus + 1 mg center dot kg(-1)center dot 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. Plasma [F-18]NS10743 passed readily into the brain, with peak uptake occurring in alpha 7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUVmax was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUVmax 1.53 +/- 0.32). Administration of NS6740 significantly decreased [F-18]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 BPND. The baseline BPND 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 BPND in regions with high [F-18]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BPND in low binding regions (cerebellum: -16%, p = 0.2). This study confirms the potential of [F-18]NS10743 as a target-specific radiotracer for the molecular imaging of central alpha 7 nAChRs by PET.