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Citalopram: Labelling with carbon-11 and evaluation in rat as a potential radioligand for in vivo PET studies of 5-HT re-uptake sites

1991; Elsevier BV; Volume: 18; Issue: 3 Linguagem: Inglês

10.1016/0883-2897(91)90130-d

1878-2140

S.P. Hume, Claudio Pascali, Victor W. Pike, David R. Turton, R. G. Ahier, R. Myers, D.M. Bateman, J. E. Cremer, Luisa G. Manjil, Raymond J. Dolan,

Advanced MRI Techniques and Applications

In vivo autoradiography of [N-methly-3H]citalopram in rat brain shows a differential regional localization which correlates with the localization of 5-HT re-uptake binding sites defined in vitro. A comparison of the biodistribution of [N-mrthyl-3H]citalopram over 2 h after i.v. injection in (1) control rats (2) rats pre-dosed with either citalopram or paroxetine and (3) rats chemically-lesioned with p-chloroamphetamine provides an estimate of specific binding relative to total binding in vivo. The ratio of binding in certain regions (e.g. cingulate) to binding in a reference tissue (e,g, cerebellum) at 30–120 min post injection is c. 1.4. In view of these results a method was developed for labelling citalopram with carbon-11 (t12 = 20.3 min, β+ = 99.8%) to provide a potential radioligand for studies using positron emission tomography. Thus, reaction of nca [11C]iodomethane, prepared from cyclotron-produced [11C]carbon dioxide, with norcitalopram in ethanol containing 2,2,6,6-tetramethyl-piperidine for 5 min at 95 °C gives crude [N-methyl-11C]citalopram in 60% radiochemical yield, decay-corrected. HPLC on silica gel provides radiochemically and chemically pure [N-methyl-11C]citalopram, as assessed by TLC, HPLC and MS. This product (isolated radiochemical yield, 49%) is easily formulated for i.v. injection. Up to 2GBq of formulated product with a specific activity of c. 15 GBq/μmol have been prepared within 40min from the end of radionuclide production. The described radiosynthesis has also been applied to give the single biologically active (+)-enantiomer of [N-methyl-11C]citalopram rather than the racemate. This product gives enhanced specific signal in the rat following i.v. injection, the ratio of uptake in regions of interest relative to cerebellum approaching 2 at 90 min.