Bonab A A, Fischman A J, Alpert N M
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
J Nucl Med. 2000 Jun;41(6):1086-92.
2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop-1-en -3-yl) nortropane (IACFT) is a highly selective ligand for dopamine transporter (DAT) sites in the striatum. Recent reports have described the basic kinetics, neurobiology, and imaging properties of [123I]IACFT. This report focuses on the structural (i.e., the ability to produce consistent binding estimates) validity of 4 methods to quantify striatal binding potential (BP) for IACFT.
Seven healthy volunteers and 8 patients with Parkinson's disease were subjects for this study. Dynamic SPECT images and arterial blood samples were acquired during the 1.5-2 h after injection of 185-370 MBq [123I]IACFT. Plasma radioactivity was analyzed chromatographically to obtain metabolite-corrected arterial input functions. The k3/k4 ratio (BP) for striatal DAT sites was calculated by 4 methods. In the first method, tissue time-activity curves and metabolite-corrected arterial input functions were analyzed by a linear graphic method developed for reversible receptor ligands. The second method was also graphic; however, the occipital cortex time-activity curve was used as the input function. In the third method, the difference between the striatal and occipital cortex time-activity curves at secular equilibrium was taken to represent bound tracer, the occipital cortex time-activity curve was used to represent tracer in the free and nonspecifically bound state, and equilibrium receptor equations were used to determine BP. The fourth method used the occipital cortex time-activity curve to mathematically derive an input function for fitting the striatal time-activity curve and to determine BP.
Analysis of the dynamic SPECT data by methods 1 and 2 resulted in highly linear plots (after approximately 15 min), supporting the reversibility of the tracer. A high linear correlation was found for BP determined by all 4 methods. ANOVA showed that methods 1-3 were indistinguishable; method 4 yielded lower BPs than did methods 1-3.
These results show that BP can be estimated consistently using 4 different methods. This finding lends support to the modeling assumptions and provides methods suitable for clinical investigation.
2β - 甲氧羰基 - 3β -（4 - 氟苯基）- N -（1 - 碘丙 - 1 - 烯 - 3 - 基）去甲托烷（IACFT）是纹状体中多巴胺转运体（DAT）位点的高度选择性配体。最近的报告描述了[123I]IACFT的基本动力学、神经生物学和成像特性。本报告重点关注定量IACFT纹状体结合潜能（BP）的4种方法的结构有效性（即产生一致结合估计值的能力）。
7名健康志愿者和8名帕金森病患者参与了本研究。在注射185 - 370 MBq [123I]IACFT后的1.5 - 2小时内采集动态SPECT图像和动脉血样本。通过色谱法分析血浆放射性以获得代谢物校正的动脉输入函数。纹状体DAT位点的k3/k4比值（BP）通过4种方法计算。第一种方法是通过为可逆受体配体开发的线性图形方法分析组织时间 - 活性曲线和代谢物校正的动脉输入函数。第二种方法也是图形法；然而，枕叶皮质时间 - 活性曲线用作输入函数。第三种方法是在长期平衡时，用纹状体和枕叶皮质时间 - 活性曲线的差值代表结合的示踪剂，枕叶皮质时间 - 活性曲线用于代表游离和非特异性结合状态的示踪剂，并使用平衡受体方程确定BP。第四种方法使用枕叶皮质时间 - 活性曲线通过数学推导得出用于拟合纹状体时间 - 活性曲线并确定BP的输入函数。
方法1和2对动态SPECT数据的分析产生了高度线性的图（大约15分钟后），支持示踪剂的可逆性。所有4种方法测定的BP之间存在高度线性相关性。方差分析表明方法1 - 3没有差异；方法4得出的BP低于方法1 - 3。
这些结果表明可以使用4种不同方法一致地估计BP。这一发现支持了建模假设，并提供了适用于临床研究的方法。
