Radiosynthesis and evaluation of N-(3-[18F]fluoropropyl)paroxetine as a radiotracer for in vivo labeling of serotonin uptake sites by PET.
To visualize serotonin uptake sites by positron emission tomography (PET), N-(3-[18F]fluoropropyl)-paroxetine ([18F]FPP), a derivative of the selective serotonin uptake blocker paroxetine, was synthesized from 3-[18F]fluoropropyltosylate and paroxetine via a one-pot procedure. The rate of formation of [18F]FPP was a function of the ratio of the initial amount of paroxetine to that of 1,3-propanediol bistosylate with which [18F]fluoropropyltosylate was synthesized. When the reaction mixture contained an excess amount of paroxetine over that of the propyl-bistosylate, the radiosynthesis followed by HPLC purification, which took approx. 90 min, gave [18F]FPP in a radiochemical yield of approx. 8%, and in high radiochemical and chemical purity. The specific activity was 2640 +/- 360 mCi/mumol. The brain biodistribution of [18F]FPP showed no distinguishable localization in regions with high density of serotonin uptake sites such as hypothalamus or olfactory tubercles. In vitro binding assays revealed that N-fluoropropylation of paroxetine reduced the affinity for the serotonin uptake site by three orders of magnitude.
Suehiro
M
M
Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205-2179.
Wilson
A A
AA
Scheffel
U
U
Dannals
R F
RF
Ravert
H T
HT
Wagner
H N
HN
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D017374:Paroxetine / Q000031:analogs & derivatives*; D010880:Piperidines; D012701:Serotonin / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D010880:Piperidines; C072918:N-(3-fluoropropyl)paroxetine; D012701:Serotonin; D017374:Paroxetine