IN-VIVO IMAGING OF BRAIN NICOTINIC ACETYLCHOLINE-RECEPTORS WITH 5-[I-123]IODO-A-85380 USING SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY

The distribution and kinetics of 5-[I-123]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was high est in the thalamus, intermediate in the frontal cortex and basal gang lia, and lowest in the cerebellum. The ratio of specific to nonspecifi c binding (V-3'') in the thalamus, estimated from the (thalamic - cere bellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h po st-injection. Specific binding was reduced by subcutaneous injection o f 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduc ed by 84 %, in the frontal cortex, by 76%, and in the basal ganglia, b y 57 % of the level measured at the time of cytisine administration, d emonstrating that the binding was reversible. On the basis of these fi ndings, together with other data indicating high affinity, receptor su btype selectivity, low nonspecific binding and lack of toxicity in ani mals, 5-[I-123]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain. Published by Elsevier Science I nc.