Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: Potential radiotracer for mapping central cholinergic innervation in vivo

Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane, 5 (4-HIPP), was synthesized and evaluated as a simple vesamicol-like radiotracer for mapping cholinergic pathways in the brain. Both enantiomers of 5 exhibit significant accumulation (approx. 2% of injected dose) and prolonged retention ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{> 3 h}$) within the rat brain. The accumulation of radioiodinated 5 in the rat brain was reduced by up to 70% in the presence of vesamicol and its analogs. The levorotary isomer (−)-4-[¹²³I)HIPP exhibits significant accumulation in the monkey brain, with a half-life of about 9 h. Radioiodinated 5 may therefore be a useful tool for studying cholinergic pathways in the brain.