Measuring α4β2∗Nicotinic Acetylcholine Receptor Densityin Vivowith [18F]nifene PET in the Nonhuman Primate

[ 18 F]Nifene is an agonist PET radioligand developed to image α4β2 ∗ nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density ( B max ) of α4β2 ∗ nAChRs and the in vivo (apparent) dissociation constant ( K Dapp ) of [ 18 F]nifene. Multiple-injection [ 18 F]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 [ 18 F]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/mL. 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 [ 18 F]nifene for measuring α4β2 ∗ nAChR B max in vivo in the rhesus monkey with a single PET experiment.