Evaluation of an image-derived input function for kinetic modeling of nicotinic acetylcholine receptor-binding PET ligands in mice

Thumbnail Image
Date
2023-10-24
Authors
Zammit, Matthew
Kao, Chien-Min
Zhang, Hannah J.
Tsai, Hsiu-Ming
Holderman, Nathanial
Mitchell, Samuel
Tanios, Eve
Bhuiyan, Mohammed
Freifelder, Richard
Kucharski, Anna
Green, William N.
Mukherjee, Jogeshwar
Chen, Chin-Tu
Alternative Title
Date Created
Location
DOI
10.3390/ijms242115510
Related Materials
Replaces
Replaced By
Keywords
Kinetic modeling
Nicotine
Addiction
PET
Nifene
2-FA85380
Abstract
Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[18F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [18F]Nifene, displaying similar pKa and binding affinity to nicotine. Time–activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the β2-subunit for ligand binding, and acute nicotine-treated mice, whereas reference tissue binding displayed high variation between groups. Binding potential estimated from a two-tissue compartment model fit of the data with the image-derived input function were higher than estimates from reference tissue-based estimations. Rate constants of radioligand dissociation were very slow for 2-FA and very fast for Nifene. We conclude that using an image-derived input function for kinetic modeling of nicotinic PET ligands provides suitable results compared to reference tissue-based methods and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.
Description
© The Author(s), 2023. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Zammit, M., Kao, C.-M., Zhang, H. J., Tsai, H.-M., Holderman, N., Mitchell, S., Tanios, E., Bhuiyan, M., Freifelder, R., Kucharski, A., Green, W. N., Mukherjee, J., & Chen, C.-T. (2023). Evaluation of an image-derived input function for kinetic modeling of nicotinic acetylcholine receptor-binding PET ligands in mice. International Journal of Molecular Sciences, 24(21), https://doi.org/10.3390/ijms242115510.
Embargo Date
Citation
Zammit, M., Kao, C.-M., Zhang, H. J., Tsai, H.-M., Holderman, N., Mitchell, S., Tanios, E., Bhuiyan, M., Freifelder, R., Kucharski, A., Green, W. N., Mukherjee, J., & Chen, C.-T. (2023). Evaluation of an image-derived input function for kinetic modeling of nicotinic acetylcholine receptor-binding PET ligands in mice. International Journal of Molecular Sciences, 24(21).
Cruises
Cruise ID
Cruise DOI
Vessel Name
Except where otherwise noted, this item's license is described as Attribution 4.0 International