Receptor subtype distribution from PET occupancy studies: Novel analysis of maximum occupancy images using a...

The Lassen plot filter (LPF) is a novel quantitative approach for generating voxel-level parametric images of half maximal effective concentration (EC₅₀) and maximum occupancy (Occ_max) from PET brain occupancy data. We applied LPF to an occupancy study of a 5HT₆ selective antagonist, PF05212377 (SAM760) using the non-selective 5HT₆/5HT_2A tracer, [¹¹C]GSK215083. We now introduced the occupancy derived B_max ratio (ODBR) as a new parameter reflecting receptor density ratios in vivo. Ten healthy subjects underwent baseline, post-drug, and washout PET scans after single oral doses (2-60 mg). LPF-derived occupancy images were produced in the striatum, yielding Occ_max values of 0.74 in the caudate and 0.87 in the putamen. The ODBR for 5HT_2A receptors was calculated from incomplete occupancy (1 - Occ_max) and binding potential ratios (ODBR = 2.88; B_max caudate (5HT_2A)/B_max putamen (5HT_2A)). This result is consistent with published postmortem B_max ratio (1.50-2.41). In general, our approach allows estimation when occupancy studies are performed with a selective drug and a non-selective tracer.