1. Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate.
- Author
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Hillmer AT, Wooten DW, Slesarev MS, Ahlers EO, Barnhart TE, Schneider ML, Mukherjee J, and Christian BT
- Subjects
- Animals, Brain metabolism, Female, Fluorine Radioisotopes, Kinetics, Macaca mulatta, Male, Protein Binding, Pyridines administration & dosage, Pyridines blood, Pyrroles administration & dosage, Pyrroles blood, Brain diagnostic imaging, Models, Biological, Positron-Emission Tomography methods, Pyridines pharmacokinetics, Pyrroles pharmacokinetics, Receptors, Nicotinic metabolism
- Abstract
[(18)F]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 [(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 Bmax values and a global value of KDapp. The fast kinetic properties of [(18)F]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 [(18)F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment.
- Published
- 2013
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