A local-neighborhood Lassen plot filter for creating occupancy and non-displaceable binding images

Abstract

For radioligands without a reference region, the Lassen plot can be used to estimate receptor occupancy by an exogenous drug ([Formula: see text]). However, the Lassen plot is not well-suited for spatial variation in [Formula: see text]. To overcome this limitation, we introduce a Lassen plot filter, i.e. a Lassen plot applied to local neighborhoods in PET images. Image data were simulated with regional variation in [Formula: see text], [Formula: see text], both, or neither and analyzed using the change in binding potential ([Formula: see text]), the conventional Lassen plot, and the Lassen plot filter at the region of interest (ROI) and voxel level. All methods were also applied to a human [11C]flumazenil occupancy study using PF-06372865. This combination of a non-selective radioligand and selective drug should lead to varying [Formula: see text]provided the distribution of subtypes varies spatially. In contrast with [Formula: see text] and the conventional Lassen plot, ROI-level and voxel-level Lassen plot filter estimates remained unbiased in the presence of regional variation in [Formula: see text] or [Formula: see text]. In the [11C]flumazenil data-set, [Formula: see text] was shown to vary regionally in accordance with the distribution of binding sites for [11C]flumazenil and PF-06372865. We demonstrate that a local-neighborhood Lassen plot filter provides robust and unbiased estimates of [Formula: see text] and [Formula: see text] without the need for any user intervention.