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 ($O^{\mathrm{Drug}}$). However, the Lassen plot is not well-suited for spatial variation in $O^{\mathrm{Drug}}$. 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 $V_{ND}$, $O^{\mathrm{Drug}}$, both, or neither and analyzed using the change in binding potential (${\Delta BP}_{ND}$), 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 $O^{\mathrm{Drug}}$provided the distribution of subtypes varies spatially. In contrast with ${\Delta BP}_{ND}$ and the conventional Lassen plot, ROI-level and voxel-level Lassen plot filter estimates remained unbiased in the presence of regional variation in $V_{ND}$ or $O^{\mathrm{Drug}}$. In the [¹¹C]flumazenil data-set, $O^{\mathrm{Drug}}$ 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 $O^{\mathrm{Drug}}$ and $V_{ND}$ without the need for any user intervention.