The outcome measure VT/fP (regional activity divided by free plasma parent between 6 and 8 hours), was used to correct for possible differences in radiotracer metabolism or plasma protein binding between groups and subjects. Specifically, VT/fP equals [123I]5-IA uptake in a region-of-interest (kBq/cc) / free plasma parent (kBq/mL)52. We refer to VT/fP as β2*-nAChR availability because we are only measuring receptors that are “available” to be bound by radiotracer. Receptors that are already occupied, e.g., by residual nicotine, a pharmacologically active metabolite (cotinine or nornicotine) or by endogenous neurotransmitter (acetylcholine) are not available. VT/fP is proportional to the binding potential (BP, mL/g=Bmax/KD), which is proportional to the receptor number (Bmax) at equilibrium, given the assumptions that there is no change in affinity (KD) and that nondisplaceable (nonspecific and free) uptake does not differ between subjects or comparison groups. As described previously43, there is no appropriate reference region for this radiotracer, so nondisplaceable [123I]5-IA uptake could not be measured. The measures of total plasma parent (kBq/mL), fP and free plasma parent (kBq/mL) which is defined as total parent * fP were compared between groups to determine differences in radiotracer metabolism or protein binding.
