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.

Abstract

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) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro 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) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.

• Authors: K A Bergström, C Halldin, A Savonen, Y Okubo, J Hiltunen, K Nobuhara, C G Swahn, P Karlsson, D McPherson, F F Knapp Jr, S Larsson, P O Schnell, L Farde
• Journal: European journal of nuclear medicine (Eur J Nucl Med) Vol. 26 Issue 11 Pg. 1482-5 (Nov 1999) ISSN: 0340-6997 [Print] Germany
• PMID: 10552091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Iodine Radioisotopes
• Ligands
• Muscarinic Antagonists
• Quinuclidines
• Receptors, Muscarinic
• 1-azabicyclo(2.2.2)oct-3-yl 2-hydroxy-2-(1-iodo-1-propen-3-yl)-2-phenylacetate

Topics

• Alzheimer Disease (diagnostic imaging)
• Animals
• Brain (diagnostic imaging)
• Iodine Radioisotopes
• Ligands
• Macaca fascicularis
• Male
• Muscarinic Antagonists
• Quinuclidines
• Receptors, Muscarinic (analysis)
• Tomography, Emission-Computed, Single-Photon