An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate

Introduction[18F]Mefway is a serotonin 5-HT1A PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [18F]mefway permits 18F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[18F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[18F]mefway and trans-[18F]mefway to evaluate the properties of cis-[18F]mefway for 5-HT1A PET imaging.MethodsThe cis- and trans-[18F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [18F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time–activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BPND) using the CB as a reference region.ResultsAveraged over the two subjects, BPND values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[18F]mefway and cis-[18F]mefway, respectively.ConclusionThe cis-labeled [18F]mefway tracer has low specific binding throughout the 5-HT1A regions of the brain compared to trans-[18F]mefway, suggesting that the target-to-background binding of cis-[18F]mefway may limit its use for in vivo assessment of 5-HT1A binding.