Marine Biological Laboratory

Permanent URI for this community

https://hdl.handle.net/1912/3

The Marine Biological Laboratory is an international center for research, education, and training in biology, biomedicine, and ecology.

Learn more about the MBL.

Browse

Browsing Marine Biological Laboratory by Subject "2-FA85380"
  • Article
    Evaluation of an image-derived input function for kinetic modeling of nicotinic acetylcholine receptor-binding PET ligands in mice
    (MDPI, 2023-10-24) 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
    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.