PT  - JOURNAL ARTICLE
AU  - Ansel T. Hillmer
AU  - Dustin W. Wooten
AU  - Maxim S. Slesarev
AU  - Elizabeth O. Ahlers
AU  - Todd E. Barnhart
AU  - Dhanabalan Murali
AU  - Mary L. Schneider
AU  - Jogeshwar Mukherjee
AU  - Bradley T. Christian
TI  - PET Imaging of α4β2* Nicotinic Acetylcholine Receptors: Quantitative Analysis of <sup>18</sup>F-Nifene Kinetics in the Nonhuman Primate
AID  - 10.2967/jnumed.112.103846
DP  - 2012 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1471--1480
VI  - 53
IP  - 9
4099  - http://jnm.snmjournals.org/content/53/9/1471.short
4100  - http://jnm.snmjournals.org/content/53/9/1471.full
SO  - J Nucl Med2012 Sep 01; 53
AB  - The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene) is an α4β2* nicotinic acetylcholine receptor (nAChR) agonist developed to provide accelerated in vivo equilibrium compared with existing α4β2* radioligands. The goal of this work was to analyze the in vivo kinetic properties of 18F-nifene with both kinetic modeling and graphical analysis techniques. Methods: Dynamic PET experiments were performed on 4 rhesus monkeys (female; age range, 9–13 y) using a small-animal PET scanner. Studies began with a high-specific-activity 18F-nifene injection, followed by a coinjection of 18F-nifene and unlabeled nifene at 60 min. Sampling of arterial blood with metabolite analysis was performed throughout the experiment to provide a parent radioligand input function. In vivo kinetics were characterized with both a 1-tissue-compartment model (1TCM) and a 2-tissue-compartment model, Logan graphical methods (both with and without blood sampling), and the multilinear reference tissue model. Total distribution volumes and nondisplaceable binding potentials (BPND) were used to compare regional binding of 18F-nifene. Regions examined include the anteroventral thalamus, lateral geniculate body, frontal cortex, subiculum, and cerebellum. Results: The rapid uptake and binding of 18F-nifene in nAChR-rich regions of the brain was appropriately modeled using the 1TCM. No evidence for specific binding of 18F-nifene in the cerebellum was detected on the basis of the coinjection studies, suggesting the suitability of the cerebellum as a reference region. Total distribution volumes in the cerebellum were 6.91 ± 0.61 mL/cm3. BPND values calculated with the 1TCM were 1.60 ± 0.17, 1.35 ± 0.16, 0.26 ± 0.08, and 0.30 ± 0.07 in the anteroventral thalamus, lateral geniculate body, frontal cortex, and subiculum, respectively. For all brain regions, there was a less than 0.04 absolute difference in the average BPND values calculated with each of the 1TCM, multilinear reference tissue model, and Logan methods. Conclusion: The fast kinetic properties and specific regional binding of 18F-nifene promote extension of the radioligand into preclinical animal models and human subjects.