[(18)F]CFT synthesis and binding to monoamine transporters in rats

BACKGROUND: We present the electrophilic synthesis of [(18)F]2β-carbomethoxy-3β-(4-fluoro)tropane [[(18)F]CFT] and the pharmacological specificity and selectivity of [(18)F]CFT for monoamine transporters in the brain and peripheral organs of rats. The human radiation dose is extrapolated from the animal data. METHODS: [(18)F]CFT was synthesized by electrophilic fluorination of a stannylated precursor by using post-target-produced [(18)F]F(2 )as a fluorinating agent. The ex vivo (18)F-activity biodistribution of [(18)F]CFT in the brain of rats was studied by autoradiography. The binding of [(18)F]CFT to the monoamine transporters was studied using in vivo blocking experiments with dopamine transporter [DAT], norepinephrine transporter [NET], or serotonin transporter [SERT] inhibitors. In vivo animal positron emission tomography was used as a comparative method to determine tracer kinetics. Human radiation dose was assessed using OLINDA software. RESULTS: The radiochemical yield of [(18)F]CFT from the initial [(18)F]F(-), decay corrected to the end of bombardment, was 3.2 ± 1.0%. The specific activity [SA] was 14.5 ± 3.4 GBq/μmol, decay corrected to the end of synthesis. Radiochemical purity exceeded 99%. DAT-specific binding was found in the striatum, locus coeruleus, and pancreas. NET-specific binding was found in the locus coeruleus. SERT-specific binding was not found in any of the studied organs. Effective dose equivalent [EDE] estimated for the standard human model was 12.8 μSv/MBq. Effective dose [ED] was 9.17 μSv/MBq. CONCLUSIONS: Post-target-produced high-SA [(18)F]F(2 )was used to incorporate(18)F directly into the phenyl ring of [(18)F]CFT. The final product had high radiochemical and chemical purities and a high SA for DAT and NET studies in vivo. In periphery, [(18)F]CFT showed a specific uptake in the pancreas. EDE and ED corresponded well with other(18)F-radioligands.