Tomographic imaging of central nicotinic acetylcholine receptors (nAChRs) via single photon emission computed tomography (SPECT) has been hampered by the lack of a radioligand with suitable in vivo binding characteristics. Therefore, a novel analog of epibatidine, (±)-exo-2-(2- iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), labeled with [125I] or [123I] was evaluated as an in vivo marker of central nicotinic acetylcholine receptors (nAChRs). [125I]IPH showed substantial brain penetration (4.2% of the injected dose at 30 min) and a cerebral biodistribution in mice consistent with the in vivo labeling of nAChRs (% injected dose/gram of thalamus, superior colliculi >> cerebellum). [125I]IPH binding sites were shown to be saturable with unlabeled IPH (ED50 approximately 1 μg/kg). The uptake of [125I]IPH was blocked significantly by the nicotinic agonists, cytisine, lobeline, and (-)- nicotine, but not by the noncompetitive nAChR antagonist, mecamylamine. Antagonists of muscarinic (scopolamine), serotonin (ketanserin), and opioid (naloxone) receptors had no significant effect on[125I]IPH binding, A preliminary SPECT imaging study with [125I]IPH in a baboon showed [123I]IPH to localize in nAChR-rich areas of brain (thalamus > frontal cortex > cerebellum). [123I]IPH binding in baboon brain was also displaced (35-45% displacement) by a challenge dose of cytisine showing that a well- characterized nicotinic agonist effectively competes for [123I]IPH binding sites. [123I]IPH seems well suited for imaging studies of nAChRs and, to our knowledge, is the first SPECT agent that has allowed for the visualization of nAChRs in primate brain.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Aug 1 1997|
- Nicotinic acetylcholine receptor
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience