Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M-1 and M-2 muscarinic acetylcholine receptors in Alzheimer's disease

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen- 3-yl)-alpha-phenylacetate(Z-IQNP) has high affinity to the M-1 and M-2 musc arinic acetylcholine receptor (mAChR) subtypes according to previous in vit ro and in vivo studies in rats. In the present study iodine-123 labelled Z- IQNP was prepared for in vivo single-photon emission tomography (SPET) stud ies in cynomolgus monkeys. SPET studies with Z-[I-123]IQNP demonstrated hig h accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and ma rked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the nonselective mAChR anta gonist scopolamine (0.2 mg/kg) inhibited Z-[I-123]IQNP binding in all these regions. The percentage of unchanged Z-[I-123]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolys is, as has been demonstrated previously with the E-isomer of IQNP. Z-[I-123 ]IQNP showed higher uptake in M-2-rich regions, compared with previously ob tained results with E-[I-123]IQNP. In conclusion, the radioactivity distrib ution from Z-[I-123]IQNP in monkey brain indicates that Z-[I-123]IQNP binds to the M-1- and M-2-rich areas and provides a high signal for specific bin ding, and is thus a potential ligand for mAChR imaging with SPET.