ΔBP, estimated receptor signal change (%); C, MR309 plasma concentration at the start of the post-dose PET-CT scan, Emax, maximum attainable signal change; EC50 , MR309 plasma concentration corresponding to 50% of the maximal signal change; δ, Hill slope. Model 1 was selected as the optimal model to describe the relationship between MR309 plasma concentration and σ1R occupancy based on goodness of fit and Akaike information criterion (AIC) values. While Model 3 (which involved fitting an EC50 and Hill slope) was favoured by AIC analysis, the precision associated with the estimated parameters was lower than that associated with the simpler Model 1. Of note, the choice of model had a modest effect on the estimated EC50: 1380 ng/mL (Model 1) to 1268 ng/mL (Model 3).
Table 2 : Summary statistics for MR309 PK parameters (PK study)