Receptor subtype distribution from PET occupancy studies: Novel analysis of maximum occupancy images using a selective drug and a non-selective tracer

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 (Occmax) from PET brain occupancy data. We applied LPF to an occupancy study of a 5HT6 selective antagonist, PF05212377 (SAM760) using the non-selective 5HT6/5HT2A tracer, 11CGSK215083. We now introduced the occupancy derived Bmax 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 Occmax values of 0.74 in the caudate and 0.87 in the putamen. The ODBR for 5HT2A receptors was calculated from incomplete occupancy (1 - Occmax) and binding potential ratios (ODBR = 2.88; Bmax caudate (5HT2A)/Bmax putamen (5HT2A)). This result is consistent with published postmortem Bmax 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.