title: [An improved automated synthesis and in vivo evaluation of PET radioligand for serotonin re-uptake sites: [11C]McN5652X].
abstract: Carbon-11 labeled serotonin (5-HT) re-uptake inhibitor, [11C]McN5652X [(6S, 10bR)-trans-(+)-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl] pyrrolo-[2,1-a]-isoquinoline], has recently been reported to be favorable for studying human 5-HT re-uptake site by positron emission tomography (PET) because of its rapid and high specific binding characteristics as radioligands. [11C]McN5652X has been synthesized by S-methylation of the corresponding des-methyl precursor A with [11Cliodemthane. One serious disadvantage of this procedure, however, is the lack of stability of A. The improved method for the synthesis of A has been desired. We have found that the decomposition of A is significantly reduced by adding a protecting agent for SH groups, dithiothreitol (DTT), into the reaction medium immediately after the demethylation of McN5652X. By using this stabilized precursor A, we have developed an automated procedure giving [11C]McN5652X with 98.6 +/- 0.4% radiochemical purity in high specific activity (181.3 +/- 7.4 GBq/mumol). Preclinical evaluation of the product was carried out by injecting the solution of [11C]-McN5652X obtained by this procedure into mice. [11C]McN5652X showed the high accumulation into mouse thalamus, striatum and cerebral cortex, organs known to have high level of 5-HT receptor density, after intravenous injection. Human PET studies also showed the high uptakes of this radioligand into the thalamus, striatum and midbrain.
authors.affiliation: National Institutes of Radiological Science, Science University of Tokyo.
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Suhara
authors.forename: A
authors.initials: A
authors.lastname: Kubodera
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D007546:Isoquinolines; D012702:Serotonin Antagonists; D012701:Serotonin; C058079:McN 5652