RT Journal Article SR Electronic T1 [11C]AF150(S): An agonist PET ligand for the M1 muscarinic acetylcholine receptor JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 29 OP 29 VO 51 IS supplement 2 A1 Buiter, Hans A1 Leysen, Josee A1 Fisher, Abraham A1 Huisman, Marc A1 Knol, Dirk L. A1 Lammertsma, Adriaan A1 Windhorst, Albert YR 2010 UL http://jnm.snmjournals.org/content/51/supplement_2/29.abstract AB 29 Objectives The G protein coupled M1 muscarinic acetylcholine receptor (M1ACh-R) is the muscarinic subtype with the highest density in the brain. The aim of this study was to investigate the labelled selective M1ACh-R agonist [11C]AF150(S) as a putative agonist PET ligand. Methods Following IV administration, the time course and regional distribution of [11C]AF150(S) in rat brain was assessed using PET. Dynamic PET scans were acquired on a HRRT scanner (CTI/Siemens). Additional PET scans in the same rats were performed after pre-treatment with the M1ACh-R antagonists, pirenzepine and trihexyphenidyl, and the M4/M1ACh-R agonist xanomeline. Finally, predosing with haloperidol was used to asses potential binding of [11C]AF150(S) to σ sites. Results Uptake of [11C]AF150(S) was higher in M1ACh-Rs rich areas, such as striatum and cerebral cortex, than in M1ACh-Rs poor regions, like cerebellum and medulla oblongata. The highest regional-to-cerebellar ratios were 1.35 and 1.20 for striatum and cerebral cortex, respectively. Pirenzepine and trihexyphenidyl caused the largest reductions in cerebral cortex (24-28%) and striatum (19-22%). Reductions by xanomeline were less pronounced, possibly because the applied dose was too low. Haloperidol produced a reduction in striatum (22%), probably due to haloperidol mediated enhanced acetylcholine release as a result of dopamine D2 receptor blockade. Conclusions The agonist ligand [11C]AF150(S) provides a small, but significant, M1ACh-R related signal in vivo, warranting further evaluation as a putative PET tracer for in vivo imaging of M1ACh-R. Research Support The A.J. Coops foundation for financial support of this study