5-[I- [formula omitted]]Iodo-3(2( S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A-85380 for in vivo studies of central nicotinic acetylcholine receptors

• Published in: Life sciences (1973) Vol. 62; no. 22; pp. PL351 - PL357
• Main Authors: Musachio, John L., Scheffel, Ursula, Finley, Paige A., Zhan, Yougen, Mochizuki, Takao, Wagner, Henry N., Dannals, Robert F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 24.04.1998
• Subjects: I-123; I-125; nicotinic acetylcholine receptor; single photon emission computed tomography; I-125; I-123; single photon emission computed tomography; nicotinic acetylcholine receptor
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(98)00180-5

The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor (nAChR) radioligand 5-[I- 125 123 ]Iodo-3(2( S)-azetidinylmethoxy)pyridine, [I-125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain penetration (3.1% of the injected dose (ID) in whole brain at 15 min post-radioligand injection). Radioligand distribution was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several different nAChR agonists (A-85380, (−)-nicotine, cytisine) significantly inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01) demonstrating the high specificity of the radioligand for nAChRs. Blocking doses of the muscarinic antagonist scopolamine and the non-competitive nAChR channel blocker mecamylamine had no significant effect on radioactive uptake supporting the in vitro selectivity of [I-125]-5-IA for the nAChR component of the cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA labeled with the imaging radionuclide I-123 may prove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.