Hume S P, Pascali C, Pike V W, Turton D R, Ahier R G, Myers R, Bateman D M, Cremer J E, Manjil L G, Dolan R
MRC Cyclotron Unit, Hammersmith Hospital, London, England.
Int J Rad Appl Instrum B. 1991;18(3):339-51. doi: 10.1016/0883-2897(91)90130-d.
In vivo autoradiography of [N-methyl-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-methyl-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 (t1/2 = 20.3 min, beta + = 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 degrees 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 2 GBq of formulated product with a specific activity of c. 15 GBq/mumol have been prepared within 40 min 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.
大鼠脑内[甲基-³H]西酞普兰的体内放射自显影显示出不同的区域定位，这与体外定义的5-羟色胺再摄取结合位点的定位相关。静脉注射后2小时内，对（1）对照大鼠、（2）预先给予西酞普兰或帕罗西汀的大鼠以及（3）用对氯苯丙胺进行化学损伤的大鼠体内[甲基-³H]西酞普兰的生物分布进行比较，可估算体内特异性结合相对于总结合的情况。注射后30 - 120分钟，某些区域（如扣带回）与参考组织（如小脑）的结合比值约为1.4。鉴于这些结果，开发了一种用碳-11（半衰期=20.3分钟，β⁺=99.8%）标记西酞普兰的方法，以提供一种潜在的放射性配体用于正电子发射断层扫描研究。因此，由回旋加速器产生的[¹¹C]二氧化碳制备的nca [¹¹C]碘甲烷与去甲西酞普兰在含有2,2,6,6 - 四甲基哌啶的乙醇中于95℃反应5分钟，得到粗品[甲基-¹¹C]西酞普兰，放射性化学产率为60%（经衰变校正）。硅胶上的高效液相色谱法可提供放射性化学和化学纯的[甲基-¹¹C]西酞普兰，通过薄层色谱法、高效液相色谱法和质谱法进行评估。该产物（分离后的放射性化学产率为49%）易于配制成静脉注射制剂。从放射性核素生产结束起40分钟内，已制备出高达2 GBq、比活度约为15 GBq/μmol的制剂产品。所描述的放射性合成方法也已用于制备[甲基-¹¹C]西酞普兰的单一生物活性（+）-对映体而非外消旋体。该产物静脉注射后在大鼠体内产生增强的特异性信号，90分钟时感兴趣区域相对于小脑的摄取比值接近2。
