Erlandsson Kjell, Sivananthan Tharani, Lui Dominic, Spezzi Andrea, Townsend Caroline E, Mu Song, Lucas Richard, Warrington Steven, Ell Peter J
Institute of Nuclear Medicine, University College London, Middlesex Hospital, Mortimer Street, London, W1T 3AA, UK.
Eur J Nucl Med Mol Imaging. 2005 Nov;32(11):1329-36. doi: 10.1007/s00259-005-1912-y. Epub 2005 Aug 26.
Serotonergic brain regions play a crucial role in the modulation of emotion, and serotonergic dysfunction may contribute to several neurological disorders. [123I]ADAM is a novel SPECT tracer which binds with high affinity to serotonin transporters (SERT). The objective of this study was to compare different methods for the quantification of tracer binding and to develop a simplified single-scan protocol for this tracer, as well as to investigate its potential for characterisation of the transporter occupancy versus plasma concentration curve of a selective serotonin re-uptake inhibitor (SSRI).
Dynamic SPECT scans were performed on 16 healthy volunteers after administration of approximately 150 MBq [123I]ADAM. Data were acquired from the time of injection until approximately 5.5 h after injection in 30- or 45-min sessions. Each subject was scanned twice: with and without pre-treatment with the SSRI citalopram in various dosage regimens. The plasma concentration of citalopram (C(p)) was determined from venous samples. Images were reconstructed by filtered back-projection with scatter and attenuation correction. Tracer binding was quantified for midbrain, striatum and thalamus using cerebellum as a reference region. Quantification was done by kinetic modelling, graphical analysis and multi-linear regression, as well as by the ratio method, with binding potential (BP2) as the outcome measure. The SERT occupancy by citalopram was determined relative to the baseline scan for each subject, and the occupancy versus C(p) curve was fitted with the E(max) model.
The highest binding of [123I]ADAM was in midbrain (mean baseline BP2+/-SD=1.31+/-0.29), with lower binding in thalamus (0.79+/-0.16) and striatum (0.66+/-0.13). There was good agreement between BP2 values obtained by different quantification methods. Using the ratio method, the best agreement with kinetic modelling was obtained with data from the time interval [200,260] min after injection. The fitting of the midbrain occupancy curve yielded a maximum occupancy of 84% and a plasma concentration required to reach 50% of the maximum of 2.5 ng/ml, with a goodness-of-fit variability of 13% (SD).
Binding of [123I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.
血清素能脑区在情绪调节中起关键作用，血清素能功能障碍可能导致多种神经疾病。[123I]ADAM是一种新型单光子发射计算机断层显像（SPECT）示踪剂，它与血清素转运体（SERT）具有高亲和力结合。本研究的目的是比较不同的示踪剂结合定量方法，并为该示踪剂开发一种简化的单次扫描方案，以及研究其对选择性血清素再摄取抑制剂（SSRI）转运体占有率与血浆浓度曲线进行特征化分析的潜力。
对16名健康志愿者给予约150MBq的[123I]ADAM后进行动态SPECT扫描。从注射时开始采集数据，直至注射后约5.5小时，采集时段为30分钟或45分钟。每个受试者扫描两次：一次在不同剂量方案下预先用SSRI西酞普兰治疗，另一次不用。从静脉样本中测定西酞普兰的血浆浓度（C(p)）。图像通过带散射和衰减校正的滤波反投影重建。以小脑作为参考区域，对中脑、纹状体和丘脑的示踪剂结合进行定量。通过动力学建模、图形分析和多线性回归以及比率法进行定量，以结合潜能（BP2）作为结果测量指标。相对于每个受试者的基线扫描，确定西酞普兰对SERT的占有率，并将占有率与C(p)曲线用E(max)模型拟合。
[123I]ADAM在中脑的结合最高（平均基线BP2±标准差=1.31±0.29），在丘脑（0.79±0.16）和纹状体（0.
