18F-labelled vesamicol derivatives: syntheses and preliminary in vivo small animal positron emission tomography evaluation.
As possible presynaptic tracers for cholinergic function in humans, three 18F-labelled vesamicol analogs were synthesized for use in positron emission tomography (PET): cis-[18F]-4-fluoromethylvesamicol (FMV), [18F]-N-fluoroacetamidobenzovesamicol (FAA) and [18F]-N-ethyl-N-fluoroacetamidobenzovesamicol (NEFA). Radiolabelling was accomplished using [18F]fluoride and the corresponding tosylates, the syntheses of which are also described. Yields were on the order of 40-60, 5 and 40-60%, respectively. Dynamic studies of the biodistribution in rats of [18F]FAA and [18F]NEFA using PET were compared with those previously reported for [18F]FMV. Due to probable rapid metabolism, [18F]FAA was considered unsuitable as a ligand for in vivo imaging. [18F]NEFA, similar to [18F]FAA, displayed a more moderate cerebral uptake than that of [18F]FMV (2 vs 20-30%). Pretreatment with vesamicol blocked the cerebral uptake, indicating a specific interaction with the vesamicol binding site. The biodistribution of high specific activity [18F]NEFA with time could be described with a three-compartmental model. The evaluation of [18F]NEFA as a tracer for cholinergic function is currently being pursued in monkeys and humans.
Rogers
G A
GA
Clinical Neurophysiology, Karolinska Hospital, Stockholm.
Stone-Elander
S
S
Ingvar
M
M
Eriksson
L
L
Parsons
S M
SM
Widén
L
L
D000818:Animals; D005069:Evaluation Studies as Topic; D005462:Fluorine Radioisotopes; D008297:Male; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis*; D051381:Rats; D017208:Rats, Wistar; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D010880:Piperidines; C006189:vesamicol