Friedrichsen Karl A, Judge Bradley A, Jones Lynne A, Rajamanickam Jayashree, Qiu Lin, Soda Anil Kumar, Rahmani Farzaneh, Benzinger George R, King Christopher R, Chaney Aisling M, Nickels Michael L, Gropler Robert J, Raji Cyrus A, White Robert L, Perlmutter Joel S, Laforest Richard, An Hongyu, Tu Zhude, Benzinger Tammie L S, Brier Matthew R
From the Department of Neurology (K.A.F., B.A.J., R.L.W., M.R.B.), the Mallinckrodt Institute of Radiology (L.A.J., J.R., L.Q., A.K.S., F.R., A.M.C., M.L.N., R.J.G., C.A.R., J.S.P., R.L., H.A., Z.T., T.LS.B.), Department of Anesthesiology (G.R.B., C.R.K.), and the Department of Neuroscience (J.S.P.), Washington University in St. Louis, St. Louis, Missouri, USA.
AJNR Am J Neuroradiol. 2025 Jul 28. doi: 10.3174/ajnr.A8944.
Sphingosine-1-phosphate receptor 1 (S1PR1) is a key regulator of neuroinflammation and plays a crucial role in multiple neurodegenerative diseases. [11C]CS1P1 is a novel PET tracer for measuring expression levels of S1PR1 in humans. Before widespread application, its quantification must be established and evaluated in healthy young and old adults through characterization of binding topographies, kinetics, and tracer metabolism rates.
We acquired dynamic [11C]CS1P1 emission data from 29 healthy controls and investigated the topography of [11C]CS1P1 uptake, radiolabeled metabolites of the tracer, an image-derived input function estimation, and tissue compartment modeling.
The image derived input function approximated the arterially sampled input function. Further, radiolabeled metabolites of the tracer accumulated linearly throughout the scan and demonstrated consistency across participants. A two-tissue compartment model fitted the observed emission data well, consistent with previously reported nonhuman primate studies. Kinetic modeling using the image derived input functions, corrected by population estimates of tracer metabolism, provided a good fit for tissue activity curves. Graphical Logan analysis reliably estimated volume of distribution (Vt), and Vt closely reproduced S1PR1 distribution in the brain.
In this study, we have established a quantitative [11C]CS1P1 PET processing approach using a two-tissue compartment model and imaging-derived input function with population metabolite correction. [11C]CS1P1 PET reflects S1PR1 topography and supports its use for investigating neuroinflammation in humans.
S1PR1＝ Sphingosine-1-phosphate receptor 1; Vt＝volume of distribution; IDIF＝ Image-Derived Input Function.
1-磷酸鞘氨醇受体1（S1PR1）是神经炎症的关键调节因子，在多种神经退行性疾病中起关键作用。[11C]CS1P1是一种用于测量人类S1PR1表达水平的新型正电子发射断层显像（PET）示踪剂。在广泛应用之前，必须通过对结合图谱、动力学和示踪剂代谢率的表征，在健康的年轻人和老年人中建立并评估其定量方法。
我们从29名健康对照者获取了动态[11C]CS1P1发射数据，并研究了[11C]CS1P1摄取的图谱、示踪剂的放射性标记代谢物、图像衍生输入函数估计和组织隔室建模。
图像衍生输入函数接近动脉采样输入函数。此外，示踪剂的放射性标记代谢物在整个扫描过程中呈线性积累，且在参与者之间表现出一致性。双组织隔室模型很好地拟合了观察到的发射数据，与先前报道的非人灵长类动物研究一致。使用经示踪剂代谢的群体估计校正的图像衍生输入函数进行动力学建模，能很好地拟合组织活性曲线。图形洛根分析可靠地估计了分布容积（Vt），且Vt紧密再现了大脑中S1PR1的分布。
在本研究中，我们使用双组织隔室模型和具有群体代谢物校正的图像衍生输入函数，建立了一种定量[11C]CS1P1 PET处理方法。[11C]CS1P1 PET反映了S1PR1的图谱，并支持其用于研究人类神经炎症。
S1PR1＝1-磷酸鞘氨醇受体1；Vt＝分布容积；IDIF＝图像衍生输入函数
