(+)-p-([18F]fluorobenzyl)spirotrozamicol [(+)-[18F]spiro-FBT]: synthesis and biological evaluation of a high-affinity ligand for the vesicular acetylcholine transporter (VAChT).
(+)-1'-[4-Hydroxy-1-(4-fluorobenzyl)piperidin-3-yl]spiro[1H- indene-1,4'- piperidine] {(+)-Spiro-FBT}, a high-affinity vesicular acetylcholine transporter ligand, was labeled with fluorine-18, and evaluated in the rat and monkey. In the rat brain, (+)-[18F]Spiro-FBT accumulated preferentially in the striatum, hippocampus, and cortex, brains regions containing high-to-moderate densities of cholinergic terminals. However, due to rapid metabolism, no preferential accumulation of the radiotracer was observed in corresponding regions of the monkey brain. Consequently, rapid metabolism renders (+)-[18F]Spiro-FBT unsuitable for studying cholinergic function with positron emission tomography.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis 55455, USA.
Nader
M A
MA
Ehrenkaufer
R L
RL
Khare
A B
AB
Smith
C R
CR
Morton
T E
TE
Mach
R H
RH
D000109:Acetylcholine; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D005462:Fluorine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D026901:Membrane Transport Proteins; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013572:Synaptic Vesicles; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
C119663:1'-(4-hydroxy-1-(4-fluorobenzyl)piperidin-3-yl)spiro(1H-indene-1,4'-piperidine); D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D026901:Membrane Transport Proteins; D010880:Piperidines; C493461:Slc18a3 protein, rat; D013141:Spiro Compounds; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D000109:Acetylcholine