[125/123I] 5-Iodo-3-pyridyl ethers. syntheses and binding to neuronal nicotinic acetylcholine receptors.
Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands.
Fan
H
H
Johns Hopkins University School of Medicine, Department of Radiology, Division of Nuclear Medicine, Baltimore, MD 21287, USA.
Scheffel
U A
UA
Rauseo
P
P
Xiao
Y
Y
Dogan
A S
AS
Yokoi
F
F
Hilton
J
J
Kellar
K J
KJ
Wong
D F
DF
Musachio
J L
JL
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D004987:Ethers / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D010215:Papio; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D004987:Ethers; D011725:Pyridines; D011978:Receptors, Nicotinic