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 presented.)). However, the Lassen plot is not well-suited for spatial variation in (Formula presented.). 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 presented.), (Formula presented.), both, or neither and analyzed using the change in binding potential ((Formula presented.)), 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 presented.) provided the distribution of subtypes varies spatially. In contrast with (Formula presented.) and the conventional Lassen plot, ROI-level and voxel-level Lassen plot filter estimates remained unbiased in the presence of regional variation in (Formula presented.) or (Formula presented.). In the [11C]flumazenil data-set, (Formula presented.) 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 presented.) and (Formula presented.) without the need for any user intervention.