Parkinson's disease(PD)is a neurodegenerative disease which is closely related to dopa-mine transporter(DAT),serotonin transporter(SERT),and norepinephrine transporter(NET).Posi-tron Emission Tomography(PET)probes targeting these three targets simultaneously may provide good imaging tools for PD research.In this study,Tesofensine was used as the lead compound to synthesize a novel multi-target probe[18F]11.The synthesis steps are as follows:compound 3 was dehydrated,esterified,grignard reacted and isomerized to obtain compound 7.Direct reduction of compound 7 with lithium aluminum hydride to give compound 8.Then,compound 8 was reacted with bromoethane to obtain tesfensine(9).Demethylation with 1-Chloroethyl chloroformate to give compound 10.Finally,compound 10 is reacted with 1-fluoro-3-bromopropane to give compound 11.Radioactive synthesis of the probe[18 F]11 was obtained by the"two-step,one-pot method"with compound 10 and[18F]flu-oroethyl methylbenzenesulfonate.The lipid-water partition coefficient of[18F]11 was 2.36±0.31(pH=7.4)which falls in the range of good blood-brain barrier permeability.[18F]11 was stable within 360 min in phosphate buffer solution(PBS)and fetal bovine serum(FBS).MicroPET/MR ima-ging demonstrated rapid brain uptake in normal rats.These results provided a basis for further in vivo biological evaluation.
维普
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