11C-NS14492 as a Novel PET Radioligand for Imaging Cerebral α7 Nicotinic Acetylcholine Receptors: In Vivo Evaluation and Drug Occupancy Measurements

• DOI: 10.2967/jnumed.111.088815
• Publication Date: 2011-08-10T01:17:07Z
• Authors: Anders Ettrup; Jens D. Mikkelsen; Szabolcs Lehel; Jacob Madsen; Elsebet Ø. Nielsen; Mikael Palner; Daniel B. Timmermann; Dan Peters; Gitte M. Knudsen
• Keywords: Radioligand; Radiosynthesis; Binding potential; Radioligand Assay; Free fraction

Small-molecule α₇ nicotinic acetylcholine receptor (α₇nAChR) agonists are currently validated for use as treatment cognitive disturbances in schizophrenia and Alzheimer disease. A suitable radiolabeled α₇nAChR PET tracer would be important vivo quantification of binding humans to measure occupancy drug candidates. Here, we present the radiosynthesis evaluation ¹¹C-NS14492 a selective radioligand. <b>Methods:</b> The high-affinity α₇nAChR-selective partial agonist NS14492 was by methylation its desmethyl precursor using ¹¹C-methyl triflate. Female Danish Landrace pigs were studied at baseline after intravenous administration blocking doses either SSR180711 or unlabeled NS14492. given an bolus injection, scanned 90 min both blocked conditions. Arterial blood collected during scanning, plasma counted, parent compound fraction determined with radio–high-performance liquid chromatography. data quantified graphical analysis arterial input; regional distribution volumes calculated, plot. <b>Results:</b>¹¹C-NS14492 had high uptake pig brain, highest cerebral cortex thalamus accordance distribution. Pretreatment consistently decreased all examined regions, dose-dependent manner, supporting finding that radioligand binds selectively vivo. <b>Conclusion:</b> We report here is first, our knowledge, showing decline blockade. This considered promising measurements human brain.