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[18F]Nifene is an agonist PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (Bmax) of α4β2* nAChRs and the in vivo (apparent) dissociation constant (KDapp) of [18F]nifene. Multiple-injection [18F]nifene experiments with varying cold nifene masses were conducted on four rhesus monkeys with a microPET P4 scanner. Compartment modeling techniques were used to estimate regional Bmax values and a global value of KDapp. The fast kinetic properties of [18F]nifene also permitted alternative estimates of Bmax and KDapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded Bmax values of 4.8±1.4, 4.3±1.0, 1.2±0.4, and 1.2±0.3 pmol/mL in the regions of antereoventral thalamus, lateral geniculate, frontal cortex, and subiculum, respectively. The KDapp of nifene was 2.4±0.3 pmol/mL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded Bmax estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [18F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment. [ABSTRACT FROM AUTHOR]

The goal of this work was to characterize the in-vivo behavior of [18F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine1A (5-HT1A) receptor density (Bmax). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [18F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of Bmax and specific binding parameters koff and kon for estimation of apparent KD. The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K1, k2, koff, Bmax, and KDapp in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with Bmax values of 42±8 and 36±8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24±4, 19±4, and 13±2 pmol/mL, respectively. The KDapp of mefway for the 5-HT1A receptor sites was 4.3±1.3 nmol/L. In conclusion, these results show that M-I [18F]mefway PET experiments can be used for the in-vivo measurement of 5-HT1A receptor density. [ABSTRACT FROM AUTHOR]