Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]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 (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.
1] Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA [2] Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ansel T
AT
Hillmer
Dustin W
DW
Wooten
Maxim S
MS
Slesarev
Elizabeth O
EO
Ahlers
Todd E
TE
Barnhart
Mary L
ML
Schneider
Jogeshwar
J
Mukherjee
Bradley T
BT
Christian
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D011725:Pyridines; D011758:Pyrroles; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C515562:nifene