| First Author | Zammit M | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 21 | PubMed ID | 37958495 |
| Mgi Jnum | J:342592 | Mgi Id | MGI:7549737 |
| Doi | 10.3390/ijms242115510 | Citation | Zammit M, et al. (2023) Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice. Int J Mol Sci 24(21) |
| abstractText | Positron emission tomography (PET) radioligands that bind with high-affinity to alpha4beta2-type nicotinic receptors (alpha4beta2Rs) 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-[(18)F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [(18)F]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 beta2-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. |
