Synthesis and evaluation of 6-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors.
Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[(18)F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[(18)F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[(18)F]fluoro-A-85380. Preliminary compartative PET studies of 6-[(18)F]fluoro-A-85380 and 2-[(18)F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.
Ding
Y
Y
Chemistry Department, Brookhaven National Laboratory, Upton, NY, USA. ding@bnl.gov
Liu
N
N
Wang
T
T
Marecek
J
J
Garza
V
V
Ojima
I
I
Fowler
J S
JS
D000818:Animals; D001384:Azetidines / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D010215:Papio; D011725:Pyridines / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000032:analysis*; D014055:Tomography, Emission-Computed
C109763:5-(2-azetidinylmethoxy)-2-chloropyridine; C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011725:Pyridines; D011978:Receptors, Nicotinic