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 ( Delta BPND), 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 [C-11]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 Delta BPND 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 [C-11]flumazenil data-set, ODrug was shown to vary regionally in accordance with the distribution of binding sites for [C-11]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.

Automated summary

This study introduces a new method, the Lassen plot filter, for estimating receptor occupancy of an exogenous drug in PET images, addressing the issue of spatial variation of ODrug. Simulated data and a human [C-11]flumazenil occupancy study demonstrated that the Lassen plot filter provides unbiased estimates in the presence of regional variation in VND or ODrug.