Assessment of alpha 7 nicotinic acetylcholine receptor availability in juvenile pig brain with [¹⁸F]NS10743

Purpose: To conduct a quantitative assessment with PET of the specific binding sites in brain of juvenile pigs for [¹⁸F]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 [¹⁸F] S10743 in a baseline condition (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 [¹⁸F]NS10743 passed readily into brain, with peak uptake occurring in α7 nAChRexpressing 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 [18F]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 cerebellum to 0.76 ± 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BPND in regions with high [¹⁸F]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).

Conclusion: This study confirms the potential of [¹⁸F]NS10743 as a target-specific radiotracer for the molecular imaging of central α7 nAChRs by PET.