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

For radioligands without a reference region, the Lassen plot can be used to estimate receptor occupancy by an exogenous drug (ODrug). However, the Lassen plot is not well-suited for spatial variation in ODrug. 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 VND, ODrug, both, or neither and analyzed using the change in binding potential (ΔBPND), 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 ODrug provided the distribution of subtypes varies spatially. In contrast with ΔBPND and the conventional Lassen plot, ROI-level and voxel-level Lassen plot filter estimates remained unbiased in the presence of regional variation in VND or ODrug. In the [11C]flumazenil data-set, ODrug 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 ODrug and VND without the need for any user intervention.