[18F]Nifene test–retest reproducibility in first‐in‐human imaging of α4β2 nicotinic acetylcholine receptors

• Published in: Synapse (New York, N.Y.) Vol. 71; no. 8
• Main Authors: Lao, Patrick J., Betthauser, Tobey J., Tudorascu, Dana L., Barnhart, Todd E., Hillmer, Ansel T., Stone, Charles K., Mukherjee, Jogeshwar, Christian, Bradley T.
• Format: Journal Article
• Language: English
• Published: United States 01.08.2017
• Subjects: Adult; Aged; Brain - diagnostic imaging; Brain - metabolism; Brain Mapping; Female; first‐in‐humans; Fluorine Radioisotopes - pharmacokinetics; Humans; Kinetics; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Protein Binding; Pyridines - pharmacokinetics; Pyrroles - pharmacokinetics; Radiopharmaceuticals - pharmacokinetics; Receptors, Nicotinic - metabolism; Reproducibility of Results; Young Adult; α4β2; positron emission tomography; α4β2; first-in-humans
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.21981

The aim of this study was to examine the suitability of [18 F]nifene, a novel α4β2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo brain imaging in a first‐in‐human study. Methods: Eight healthy subjects (4 M,4 F;21–69,44 ± 21 yrs) underwent a [18F]nifene positron emission tomography scan (200 ± 3.7 MBq), and seven underwent a second scan within 58 ± 31 days. Regional estimates of DVR were measured using the multilinear reference tissue model (MRTM2) with the corpus callosum as reference region. DVR reproducibility was evaluated with test–retest variability (TRV) and intraclass correlation coefficient (ICC). Results: The DVR ranged from 1.3 to 2.5 across brain regions with a TRV of 0–7%, and did not demonstrate a systematic difference between test and retest. The ICCs ranged from 0.2 to 0.9. DVR estimates were stable after 40 min. Conclusion: The binding profile and tracer kinetics of [18F]nifene make it a promising α4β2* nAChR radiotracer for scientific research in humans, with reliable DVR test–retest reproducibility. Fluorine‐18 labeled nifene is a novel radiotracer that binds to α4β2* nicotinic acetylcholine receptors rapidly and reliably. First‐in‐human [18F]nifene images demonstrate a pattern consistent with known α4β2* nicotinic acetylcholine receptor sites. It is suitable for in vivo investigation of addiction or neurodegenerative disease, among other things.