Abstract
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 Drove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.
Original language | English (US) |
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Pages (from-to) | PL351-PL357 |
Journal | Life Sciences |
Volume | 62 |
Issue number | 22 |
DOIs | |
State | Published - Apr 24 1998 |
Keywords
- I-123
- I-125
- Nicotinic acetylcholine receptor
- Single photon emission computed tomography
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- Pharmacology, Toxicology and Pharmaceutics(all)