Kazumata K, Dhawan V, Chaly T, Antonini A, Margouleff C, Belakhlef A, Neumeyer J, Eidelberg D
Department of Neurology, North Shore University Hospital, Manhasset, New York 11030, USA.
J Nucl Med. 1998 Sep;39(9):1521-30.
Fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (FPCIT) has been synthesized as a dopamine transporter ligand for PET studies. We evaluated the regional brain uptake and the plasma metabolism of [18F]-FPCIT.
PET studies were conducted on 7 normal subjects and on 10 patients with Parkinson's disease. After the [18F]-FPCIT injection (4.4+/-1.8 mCi), dynamic scans were acquired over 100 min. Plasma metabolite analysis was performed using high-performance liquid chromatography (HPLC).
Plasma HPLC revealed two peaks corresponding to unmetabolized [18F]-FPCIT and a polar metabolite. The fraction of the parent compound decreased rapidly to 25% at 25 min. Fluorine-18-FPCIT showed a striatum-to-occipital ratio (SOR) of 3.5 at 90 min postinjection. The ratio of striatal-to-occipital distribution volume (DVR) was calculated directly by using a mean tissue-to-plasma efflux constant for occipital cortex obtained in 10 subjects (ki=0.037 min(-1)). DVR measures determined with and without plasma input function were correlated (r=0.98, p < 0.0001). In normal subjects, a significant age-related decline of DVR was observed both for caudate and putamen, corresponding to a 7.7% and 6.4% decline per decade, respectively (r > 0.85, p < 0.01). Both DVR and SOR correctly classified early-stage Parkinson's disease patients with comparable accuracy (p < 0.0001). Age-corrected DVR values correlated negatively with the Uniform Parkinson's Disease Rating Scale composite motor ratings (r=0.66, p < 0.05).
The tracer characteristics are compatible with a high-affinity, reversible ligand. FPCIT/PET demonstrated age-related decline in dopamine transporter binding in normal subjects as well as significant reductions in patients with idiopathic Parkinson's disease, which correlates with the disease severity.
氟化N-3-氟丙基-2-β-羧甲氧基-3-β-(4-碘苯基)去甲托烷（FPCIT）已被合成作为用于PET研究的多巴胺转运体配体。我们评估了[18F]-FPCIT在脑内的区域摄取和血浆代谢情况。
对7名正常受试者和10名帕金森病患者进行了PET研究。注射[18F]-FPCIT（4.4±1.8毫居里）后，在100分钟内进行动态扫描。使用高效液相色谱法（HPLC）进行血浆代谢物分析。
血浆HPLC显示出两个峰，分别对应未代谢的[18F]-FPCIT和一种极性代谢物。母体化合物的比例在25分钟时迅速降至25%。氟-18-FPCIT在注射后90分钟时纹状体与枕叶的比值（SOR）为3.5。纹状体与枕叶分布容积比值（DVR）通过使用10名受试者枕叶皮质的平均组织-血浆流出常数（ki = 0.037分钟-1）直接计算得出。有无血浆输入函数情况下测定的DVR测量值具有相关性（r = 0.98，p < 0.0001）。在正常受试者中，观察到尾状核和壳核的DVR均随年龄显著下降，每十年分别下降7.7%和6.4%（r > 0.85，p < 0.01）。DVR和SOR对早期帕金森病患者的正确分类准确率相当（p < 0.0001）。年龄校正后的DVR值与统一帕金森病评定量表综合运动评分呈负相关（r = 0.66，p < 0.05）。
该示踪剂特性与高亲和力、可逆性配体相符。FPCIT/PET显示正常受试者中多巴胺转运体结合随年龄下降，特发性帕金森病患者中也有显著降低，且与疾病严重程度相关。
