Radiosynthesis and evaluation of N-(3-[ 18F]fluoropropyl)paroxetine as a radiotracer for in vivo labeling of serotonin uptake sites by PET

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.