使用激动剂 PET 示踪剂 11C-CUMI-101 对人体 5-羟色胺 1A 受体进行体内定量。
In vivo quantification of human serotonin 1A receptor using 11C-CUMI-101, an agonist PET radiotracer.
机构信息
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
出版信息
J Nucl Med. 2010 Dec;51(12):1892-900. doi: 10.2967/jnumed.110.076257.
UNLABELLED
The serotonin (5-hydroxytryptamine, or 5-HT) type 1A receptor (5-HT(1A)R) is implicated in the pathophysiology of numerous neuropsychiatric disorders. We have published the initial evaluation and reproducibility in vivo of [O-methyl-(11)C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione ((11)C-CUMI-101), a novel 5-HT(1A) agonist radiotracer, in Papio anubis. Here, we report the optimal modeling parameters of (11)C-CUMI-101 for human PET studies.
METHODS
PET scans were obtained for 7 adult human volunteers. (11)C-CUMI-101 was injected as an intravenous bolus, and emission data were collected for 120 min in 3-dimensional mode. We evaluated 10 different models using metabolite-corrected arterial input functions or reference region approaches and several outcome measures.
RESULTS
When using binding potential (BP(F) = B(avail)/K(D) [total available receptor concentration divided by the equilibrium dissociation constant]) as the outcome measure, the likelihood estimation in the graphical analysis (LEGA) model performed slightly better than the other methods evaluated at full scan duration. The average test-retest percentage difference was 9.90% ± 5.60%. When using BP(ND) (BP(ND) = f(nd) × B(avail)/K(D); BP(ND) equals the product of BP(F) and f(nd) [free fraction in the nondisplaceable compartment]), the simplified reference tissue method (SRTM) achieved the lowest percentage difference and smallest bias when compared with nondisplaceable binding potential obtained from LEGA using the metabolite-corrected plasma input function (r(2) = 0.99; slope = 0.92). The time-stability analysis indicates that a 120-min scan is sufficient for the stable estimation of outcome measures. Voxel results were comparable to region-of-interest-based analysis, with higher spatial resolution.
CONCLUSION
On the basis of its measurable and stable free fraction, high affinity and selectivity, good blood-brain barrier permeability, and plasma and brain kinetics, (11)C-CUMI-101 is suitable for the imaging of high-affinity 5-HT(1A) binding in humans.
未加标签
5-羟色胺（5-羟色胺，或 5-HT）1A 受体（5-HT（1A）R）参与了许多神经精神疾病的病理生理学。我们已经发表了 [O-甲基-（11）C]2-（4-（4-（2-甲氧基苯基）哌嗪-1-基）丁基）-4-甲基-1,2,4-三嗪-3,5（2H,4H）二酮（（11）C-CUMI-101）的初步评估和体内重现性，这是一种新型的 5-HT（1A）激动剂放射性示踪剂，在 Papio anubis 中。在这里，我们报告了用于人体 PET 研究的（11）C-CUMI-101 的最佳建模参数。
方法
对 7 名成年人类志愿者进行了 PET 扫描。（11）C-CUMI-101 作为静脉内推注给药，以三维模式采集 120 分钟的发射数据。我们使用代谢校正的动脉输入函数或参考区方法和几种结果测量值评估了 10 种不同的模型。
结果
当使用结合潜力（BP（F）= B（avail）/K（D）[总可用受体浓度除以平衡解离常数]）作为结果测量值时，图形分析中的似然估计（LEGA）模型的表现略优于其他在全扫描持续时间内评估的方法。平均测试-重测百分比差异为 9.90%±5.60%。当使用 BP（ND）（BP（ND）= f（nd）×B（avail）/K（D）；BP（ND）等于 BP（F）和 f（nd）的乘积[无置换隔室中的游离分数]）时，与使用代谢校正后的 LEGA 从血浆输入函数获得的非置换结合潜力相比，简化参考组织方法（SRTM）获得了最低的百分比差异和最小的偏差（r（2）=0.99；斜率=0.92）。时间稳定性分析表明，120 分钟的扫描足以稳定估计结果测量值。体素结果与基于感兴趣区域的分析相当，具有更高的空间分辨率。
结论
基于其可测量且稳定的游离分数、高亲和力和选择性、良好的血脑屏障通透性以及血浆和脑动力学，（11）C-CUMI-101 适合用于成像人类的高亲和力 5-HT（1A）结合。
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