Suehiro M, Scheffel U, Dannals R F, Ravert H T, Ricaurte G A, Wagner H N
Division of Nuclear Medicine and Radiation Health Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21205-2179.
J Nucl Med. 1993 Jan;34(1):120-7.
A radioligand for imaging central serotonin (5-hydroxytryptamine; 5-HT) uptake sites by positron emission tomography (PET) has yet to be developed. Such a tracer would be useful for the study of normal and altered serotonergic neurotransmission as well as for the detection of serotonergic neurotoxicity. This paper describes the labeling of the highly potent serotonin (5-HT) uptake blocker, McN-5652-Z (trans-1,2,3,5,6,10 beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline; racemic mixture), with 11C and the evaluation of this radiotracer in rodents with respect to its in vivo binding characteristics. In mouse brain, 11C-McN-5652-Z accumulated rapidly in regions with high densities of 5-HT uptake sites. The ratio between hypothalamus and cerebellum was 1.5:1 at 15 min and increased with time to 4.6:1 at 90 min after injection. The distribution of 11C-McN-5652 in rat brain at 60 min correlated well with regional concentrations of 5-HT uptake sites (r = 0.86). The specificity and selectivity of 11C-McN-5652 binding to the 5-HT transporter were tested by preinjecting blocking doses of known 5-HT, dopamine and norepinephrine uptake inhibitors, and a 5-HT2 receptor blocker before injection of the radiotracer. Preinjection of increasing doses of unlabeled McN-5652-Z inhibited 11C-McN-5652-Z binding in a dose-dependent fashion. These results suggest that the in vivo binding of the radiotracer was specific, selective for 5-HT uptake sites, saturable and that 11C-McN-5652-Z holds promise as a radiotracer for PET imaging of 5-HT uptake sites in the mammalian brain.
一种用于通过正电子发射断层扫描（PET）成像中枢5-羟色胺（5-羟色胺；5-HT）摄取位点的放射性配体尚未开发出来。这样一种示踪剂对于研究正常和改变的5-羟色胺能神经传递以及检测5-羟色胺能神经毒性将是有用的。本文描述了用11C标记高效5-羟色胺（5-HT）摄取阻滞剂McN-5652-Z（反式-1,2,3,5,6,10β-六氢-6-[4-(甲硫基)苯基]吡咯并-[2,1-a]-异喹啉；外消旋混合物），并在啮齿动物中评估这种放射性示踪剂的体内结合特性。在小鼠脑中，11C-McN-5652-Z在5-HT摄取位点密度高的区域迅速积累。注射后15分钟时，下丘脑与小脑的比值为1.5:1，随着时间推移，在90分钟时增加到4.6:1。注射后60分钟时，11C-McN-5652在大鼠脑中的分布与5-HT摄取位点的区域浓度相关性良好（r = 0.86）。在注射放射性示踪剂之前，通过预先注射已知的5-HT、多巴胺和去甲肾上腺素摄取抑制剂的阻断剂量以及一种5-HT2受体阻滞剂，来测试11C-McN-5652与5-HT转运体结合的特异性和选择性。预先注射递增剂量的未标记McN-5652-Z以剂量依赖方式抑制11C-McN-5652-Z的结合。这些结果表明，放射性示踪剂的体内结合具有特异性、对5-HT摄取位点具有选择性、可饱和，并且11C-McN-5652-Z有望作为一种放射性示踪剂用于哺乳动物脑中5-HT摄取位点的PET成像。
