Radiosynthesis and evaluation of N-(3-[18F]fluoropropyl)paroxetine as a radiotracer for in vivo labeling of serotonin uptake sites by PET |
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Institution: | 1. Synaptic Transmission In Vivo, Neuroscience Drug Discovery, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark;2. Sunred Pharma Consulting ApS, Svend Gønges Vej 11ADK, 2680 Solrød Strand, Denmark |
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Abstract: | To visualize serotonin uptake sites by positron emission tomography (PET), N-(3-18F]fluoropropyl)-paroxetine (18F]FPP) (Fig. 1), 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/μmol.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. |
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