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

[¹⁸F]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 [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 B_max values and a global value of K_Dapp. The fast kinetic properties of [¹⁸F]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 [¹⁸F]nifene for measuring α4β2* nAChR B_max in vivo in the rhesus monkey with a single PET experiment. [ABSTRACT FROM AUTHOR]