Measuring α4β2*nicotinic acetylcholine receptor density in vivo with [18F]nifene PET in the nonhuman primate

[F-18]Nifene is an agonist PET radioligand developed to image alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (B-max) of alpha 4 beta 2* nAChRs and the in vivo (apparent) dissociation constant (K-Dapp) of [F-18]nifene. Multiple-injection [F-18]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 B-max values and a global value of K-Dapp. The fast kinetic properties of [F-18]nifene also permitted alternative estimates of B-max and K-Dapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded B-max 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 K-Dapp of nifene was 2.4 +/- 0.3 pmol/nnL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded B-max estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [F-18]nifene for measuring alpha 4 beta 2* nAChR B-max in vivo in the rhesus monkey with a single PET experiment.