Synthesis and in vivo evaluation of fluorine-18 and iodine-123 labeled 2β-Carbo(2-fluoroethoxy)-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane as a candidate serotonin transporter Imaging agent
Synthesis and in vivo evaluation of fluorine-18 and iodine-123 labeled 2β-Carbo(2-fluoroethoxy)-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane as a candidate serotonin transporter Imaging agent
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DOI：
10.1021/jm061303s
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发表时间：
2007-09-20
影响因子：
7.3
通讯作者：
Goodman, Mark M.
中科院分区：
文献类型：
--
作者：
Plisson, Christophe;Stehouwcr, Jeffrey S.;Goodman, Mark M.
合成了用于正电子发射断层扫描和单光子发射计算机断层扫描的5-羟色胺转运体显像剂2-β-碳酸(2-氟乙氧基)-3-β-(4-‘-((Z)-2-iodoethenyl)phenyl)nortropane(PFEpZIENT，-1)。1与人单胺转运体的结合亲和力与多巴胺转运体(DAT)(Ki=13 nM)和去甲肾上腺素转运体(Net)(Ki=28 nM)相比，对SERT(K-I=0.08 nM)有很高的亲和力。在雄性大鼠体内的生物分布和阻断研究表明，[1111]1对SERT具有选择性和特异性。在一只麻醉猴体内用181711进行的microPET脑成像研究显示，间脑和脑干的摄取率很高，120min时摄取率达到峰值。(R，S)-西酞普兰中心点Hbr的追踪研究使[F-18]1放射性从所有SERT富集区移位。用DAT配体2β-碳苯氧基-3β-(4-氯苯基)托烷(9，RTI-113)进行的CHASE研究未能取代[11F]I，表明[F-18]1是SERT所特有的。[18F]L的体内评价表明，该示踪剂是一种很好的定位和定量CNS SERT的候选方法。
2 beta-Carbo(2-fluoroethoxy)-3 beta-(4 '-((Z)-2-iodoethenyl)phenyl)nortropane(PFEpZIENT, 1) was synthesized as a serotonin transporter (SERT) imaging agent for both positron emission tomography (PET) and single photon emission computerized tomography (SPECT). The binding affinity of 1 to human monoamine transporters showed a high affinity for the SERT (K-i = 0.08 nM) with respect to the dopamine transporter (DAT) (Ki = 13 nM) and the norepinephrine transporter (NET) (Ki = 28 nM). In vivo biodistribution and blocking studies performed in male rats demonstrated that [1111]1 was selective and specific for SERT. In vivo microPET brain imaging studies in an anesthetized monkey with [181711 showed high uptake in the diencephalon and brainstem with peak uptake achieved at 120 min. A chase study with (R,S)-citalopram center dot HBr displaced [F-18]1 radioactivity from all SERT-rich brain regions. A chase study with the DAT ligand 2 beta-carbophenoxy-3 beta-(4-chlorophenyl)tropane (9, RTI-113) failed to displace [11F]I, indicating that [F-18]1 is specific to the SERT. The in vivo evaluation of [18F]l indicates that this radiotracer is a good candidate for mapping and quantifying CNS SERT.