Evaluation of [¹¹C]CS1P1 in Healthy Young and Older Adults

BACKGROUND AND PURPOSE: 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.

MATERIALS AND METHODS: We acquired dynamic [¹¹C]CS1P1 emission data from 29 healthy controls and investigated the topography of [¹¹C]CS1P1 uptake, radio-labeled metabolites of the tracer, an image-derived input function estimation, and tissue compartment modeling.

RESULTS: The image-derived input function approximated the arterially sampled input function. Further, radio-labeled metabolites of the tracer accumulated linearly throughout the scan and demonstrated consistency across participants. A 2-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.

CONCLUSIONS: In this study, we have established a quantitative ¹¹C]CS1P1 PET processing approach by using a 2-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.