Facile synthesis and initial PET imaging of novel potential heart acetylcholinesterase imaging agents [11C]pyridostigmine and its analogs.
A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [11C]pyridostigmine (1), [11C]para-pyridostigmine (2) and [11C]ortho-pyridostigmine (3) were prepared by N-[11C]methylation of the precursors using [11C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60-85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10-15 min. The initial PET dynamic studies of compounds (1-3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents.
Department of Radiology, Krannert Institute of Cardiology2, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Ji-Quan
JQ
Wang
Michael A
MA
Miller
Xiangshu
X
Fei
K Lee
KL
Stone
John C
JC
Lopshire
William J
WJ
Groh
Douglas P
DP
Zipes
Gary D
GD
Hutchins
Qi-Huang
QH
Zheng
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011729:Pyridostigmine Bromide / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase; D011729:Pyridostigmine Bromide