Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
J Nucl Med. 2018 Oct;59(10):1603-1608. doi: 10.2967/jnumed.117.205492. Epub 2018 Mar 1.
Reduced density of the α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) in the cortex and hippocampus of the human brain has been reported in aging and patients with neurodegenerative disease. This study assessed the pharmacokinetic behavior of F-(-)-JHU86428 (F-XTRA), a new radiotracer for in vivo PET imaging of the α4β2-nAChR, particularly in extrathalamic regions of interest in which the α4β2-nAChR is less densely expressed than in thalamus. F-XTRA was also used to evaluate the α4β2-nAChR in the hippocampus in human aging. Seventeen healthy nonsmoker adults (11 men, 6 women; age, 30-82 y) underwent PET neuroimaging over 90 or 180 min in a high-resolution research tomograph after bolus injection of F-XTRA. Methods to quantify binding of F-XTRA to the α4β2-nAChR in the human brain were compared, and the relationship between age and binding in the hippocampus was tested. F-XTRA rapidly entered the brain, and time-activity curves peaked within 10 min after injection for extrathalamic regions and at approximately 70 min in the thalamus. The 2-tissue-compartment model (2TCM) predicted the regional time-activity curves better than the 1-tissue-compartment model, and total distribution volume (V) was well identified by the 2TCM in all ROIs. V values estimated using Logan analysis with metabolite-corrected arterial input were highly correlated with those from the 2TCM in all regions, and values from 90-min scan duration were on average within 5% of those values from 180 min of data. Parametric images of V were consistent with the known distribution of the α4β2-nAChR across the brain. Finally, an inverse correlation between V in the hippocampus and age was observed. Our results extend support for use of F-XTRA with 90 min of emission scanning in quantitative human neuroimaging of the extrathalamic α4β2-nAChR, including in studies of aging.
已有研究报道，在衰老和神经退行性疾病患者的大脑皮层和海马区，α4β2 型烟碱型乙酰胆碱受体（α4β2-nAChR）的密度降低。本研究评估了 F-(-)-JHU86428（F-XTRA）的药代动力学行为，F-XTRA 是一种新的放射性示踪剂，可用于活体 PET 成像 α4β2-nAChR，特别是在 α4β2-nAChR 表达密度低于丘脑的脑外感兴趣区。还使用 F-XTRA 评估了人类衰老过程中海马体中的 α4β2-nAChR。17 名健康不吸烟的成年人（11 名男性，6 名女性；年龄 30-82 岁）在高分辨率研究断层扫描仪中接受 F-XTRA 静脉推注后 90 或 180 分钟的 PET 神经影像学检查。比较了量化 F-XTRA 与人类大脑中 α4β2-nAChR 结合的方法，并测试了年龄与海马体结合的关系。F-XTRA 迅速进入大脑，外丘脑区域的时间-活性曲线在注射后 10 分钟内达到峰值，而丘脑区域则在大约 70 分钟时达到峰值。双室模型（2TCM）比单室模型更好地预测了区域时间-活性曲线，并且在所有 ROI 中，2TCM 均能很好地确定总分布容积（V）。使用代谢物校正动脉输入的 Logan 分析估算的 V 值与所有区域的 2TCM 值高度相关，并且 90 分钟扫描持续时间的 V 值平均与 180 分钟数据的 V 值相差 5%以内。V 的参数图像与脑内已知的 α4β2-nAChR 分布一致。最后，观察到海马体 V 值与年龄之间呈负相关。我们的研究结果进一步支持使用 F-XTRA 进行 90 分钟的发射扫描，对脑外 α4β2-nAChR 进行定量人类神经影像学研究，包括衰老研究。
