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

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.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.34). 08/2013; 33(11). DOI: 10.1038/jcbfm.2013.136
Source: PubMed

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.Journal of Cerebral Blood Flow & Metabolism advance online publication, 14 August 2013; doi:10.1038/jcbfm.2013.136.

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