匹莫范色林作为5-HT2A受体PET放射性配体的¹¹C标记及初步评估
(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand.
作者信息
Andersen Valdemar L, Hansen Hanne D, Herth Matthias M, Dyssegaard Agnete, Knudsen Gitte M, Kristensen Jesper L
机构信息
Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
出版信息
Bioorg Med Chem Lett. 2015 Mar 1;25(5):1053-6. doi: 10.1016/j.bmcl.2015.01.017. Epub 2015 Jan 20.
Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.
匹莫范色林是一种选择性5-羟色胺2A受体（5-HT2AR）反向激动剂，已显示出治疗帕金森病患者精神症状的潜力。在此，我们详细介绍了[11C]标记过程，并随后在猪身上评估了匹莫范色林作为正电子发射断层扫描（PET）放射性配体的情况。[11C]匹莫范色林是通过在60°C的丙酮中使用[11C]三氟甲磺酸甲酯（[11C]MeOTf）对合适的前体进行N-甲基化得到的，放射化学产率在1 - 1.7GBq范围内（n = 4）。在丹麦长白猪中，该放射性配体很容易进入大脑，并根据5-HT2AR的分布在皮质中显示出结合。然而，这种结合不能被酮色林或匹莫范色林本身阻断，表明存在高非特异性结合。5-HT2R拮抗剂不能使其发生置换以及在丘脑的结合情况表明，[11C]匹莫范色林在猪体内对5-HT2AR没有选择性。
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