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^18F-FECNT的生物分布特性及小动物PET显像研究 被引量:4

Biodistribution and microPET imaging of ^18F-FECNT as a dopamine transporter imaging agent
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摘要 目的探讨多巴胺转运蛋白(DAT)显像剂^18F-N-(2-氟乙基)-2β-甲酯基-3β-(4-氯苯基)去甲基托烷(FECNT)的体内生物分布特性,并进行小动物PET显像研究,以评价其临床应用潜力。方法自制^18F-FECNT注射液,进行正常小鼠脑内分布、DAT阻断实验、正常和单侧帕金森病(PD)模型大鼠小动物PET脑显像。结果正常ICR小鼠在给药后5,15,30,60,120,180min的进脑量分别达2.22,1.20,1.02,0.78,0.71,0.67百分注射剂量率(%ID)。给药后5~60min内,药物在纹状体(ST)部位浓聚,纹状体/小脑(ST/CB)比值在5,15,30,60min时分别为2.56,3.47,2.78,1.63。120min后ST的放射性浓度下降至与其他脑组织相近。脑内DAT经β-CFF阻断的小鼠,其ST未见放射性浓聚。正常大鼠小动物PFT显像图中ST显影清晰(ST/CB=2.18±0.16,n=3),双侧对称;PD模型大鼠未损毁侧ST放射性浓聚(ST未损毁侧/CB=2.01±0.23,n=3),而损毁侧ST放射性摄取不明显,与小脑相当(ST损毁侧/CB=1.04±0.05)。结论^18F-FECNT能透过无损的血脑屏障浓聚于ST,对DAT具有高亲和性与特异性,是一种有临床应用潜力的DAT显像剂。 Objective 2β-carbomethoxy-3β-(4-corophenyl)-8-(2-^18F-iluoroethyl) nortropane (^18F- FECNT ) is a recently developed dopamine transporter (DAT) imaging agent. The aim of this study was to evaluate its brain biodistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice (5 mice each group) received ^18F-FECNT were sacrificed at indicated time post injection. Different brain regions (cortex, hippocampus, striatum, cerebellum) were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β- Carbomethoxy-3β- (4-fluorphenyl) tropane (β-CFT) at before ^18F-FECNT injection. MicroPET scans were performed in both normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of ^18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose (% ID) at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 rain, respectively, post injection. The selective striatum uptake of iSF.FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro- PET exhibited symmetrical ( left/right = 1.00 ± 0.05 ) and the highest uptake of radioactivity ( striatum/cerebellum =2.18 ±0.16 at 5- 125 min, n =3 ). As for the hemiparkinsonian rats, nonsymmetrical [ unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 ( n = 3 ) vs 1.04 ± 0.05 ] and the highest uptake of radioactivity were also noted. Conclusions The results suggest that ^18F-FECNT rapidly passes through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson's disease.
出处 《中华核医学杂志》 CAS CSCD 北大核心 2009年第3期181-184,共4页 Chinese Journal of Nuclear Medicine
基金 国家自然科学基金(30570518) 江苏省高技术研究计划(BG2007603) 江苏省卫生厅科技项目(H200401)
关键词 FECNT 帕金森病 多巴胺 小鼠 大鼠 体层摄影术 发射型计算机 FECNT Parkinson disease Dopamine Mice Rats Tomography, emission-computed
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参考文献14

  • 1Poewe W,Scherfler C.Role of dopamine transporter imaging in investigation of parkinsanian syndromes in routine clinical practice.Movement Disorders,2003,18 Suppl 7:S16-S21.
  • 2Shih MC,Hoexter MQ,Andrade LA,et al.Parkinsons disease and dopamine transporter neuroimaging --a critical review.Sao Paulo Med J,2006,124:168-175.
  • 3Goodman MM,Kilts CD,Keil R,et al.^18F-1abeled FECNT:a selective radioligand for PET imaging of brain dopamine transporters.Nucl Med Biol,2000,27:1-12.
  • 4Davis MR,Votaw JR,Bremner JD,et al.Initial human PET imaging studies with the dopamine transporter ligand ^18F-FECNT.J Nucl Med,2003,44:855-861.
  • 5Deterding TA,Votaw JR,Wang CK,et al.Biodistribution and radiation dosimetry of the dopamine transporter ligand ^18F-FECNT.J Nucl Med,2001,42:376-381.
  • 6李晓敏,陈正平,傅榕赓,张同兴,王颂佩.2β-甲酯基-3β-(4-氟苯基)去甲基托烷的合成[J].化学试剂,2004,26(3):185-186. 被引量:1
  • 7Chen ZP,Wang SP,Li XM,et al.A one-step automated high-radiochemical-yield synthesis of ^18F-FECNT from mesylate precursor.Appl Radiat Isot,2008,26.1881-1885.
  • 8Bakke JL,Lawrence NL,Robinson SA,et al.Late endocrine effects of L-dopa,5-HTP,and 6-OH-dopa administered to neonatal rats.Neuroendocrinology,1978,25:291-302.
  • 9Marshall V,Grosset D.Role of dopamine transporter imaging in routine clinical practice.Mov Disord,2003,18:1415-1423.
  • 10Krause KH,Dreselb SH,Krausec J,et al.The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder.Neurosci Biobehav Rev,2003,27:605-613.

二级参考文献12

  • 1Lunkvist C, Halldin C, Ginovart N, et al. ^18F-β-CIT-FP is superior to ^11C-β-CIT-FP for quantitation of the dopamine transporter. Nud Med Bio,1997, 24: 621-627.
  • 2Chaly T, Dhawan V, Kazumata K, et al. Radiosynthesis of ^18F-N-3-fluoropropyl-2-β-carbomethoxy-3-β(4-iodophenyl) nortropane and the first human study with positron emission tomography. Nucl Med Bio, 1996.23: 999-1004.
  • 3Goodman M M,Keil R,Shoup T M,et al. Fluorine-18-FPCT:a PET radiotracer for imaging dopamine transporters. [J]. J.Nucl. Med., 1997,38(1): 119-126.
  • 4Kung M P, Stevenson D A, Plossl K, et al. [99mTc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent[J]. Eur. J. Nucl. Med., 1997,24(4) :372-380.
  • 5Elmaleh D R, Fischman A J, Shoup T M, et al. Preparation and biological evaluation of iodine-125-IACFT: a selective SPECT agent for imaging dopanine transporter sites [J]. J.Nucl. Med., 1996,37(7): 1197-1202.
  • 6Hantraye P,Brownell A L,Elmaleh D, et al. Dopamine fiber detection by[11C]-CFT and PET in a primate model of parkinsonism [J]. Neuroreport, 1992,3 (3): 265-268.
  • 7Frost J J, Rosier A J, Reich S G, et al. Positron emission tomographic imaging of the dopamine transporter with 11 C-WIN 35,428 reveals marked declines in mild Parkinscn′s disease [J]. Ann. Neurol., 1993,34(3) :423-431.
  • 8Meltzer P C, Liang A Y, Brownell A L, et al. Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging[J]. J. Med. Chem., 1993,36(7):856-862.
  • 9Rinne J O,Laihinen A,Nagren K,et al. PET examination of the monoamine transporter with[11C]beta-CIT and[11C]bea-CFT in early Parkinson′ s disease [J]. Synapse, 1995,21(2) :97-103.
  • 10方平,陈正平,林岩松,周翔,杜宜奎,王世真.多巴胺转运蛋白显像剂^(18)F-FP-β-CIT的制备[J].同位素,2001,14(1):6-10. 被引量:5

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