{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:35:18Z","timestamp":1760150118357,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA044760","RF1 AG029479","T32 DA043469"],"award-info":[{"award-number":["R01 DA044760","RF1 AG029479","T32 DA043469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA044760","RF1 AG029479","T32 DA043469"],"award-info":[{"award-number":["R01 DA044760","RF1 AG029479","T32 DA043469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA044760","RF1 AG029479","T32 DA043469"],"award-info":[{"award-number":["R01 DA044760","RF1 AG029479","T32 DA043469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Positron emission tomography (PET) radioligands that bind with high-affinity to \u03b14\u03b22-type nicotinic receptors (\u03b14\u03b22Rs) 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\u2013activity curves of the left ventricle of the heart displayed similar distribution across wild type mice, mice lacking the \u03b22-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.<\/jats:p>","DOI":"10.3390\/ijms242115510","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:28:25Z","timestamp":1698128905000},"page":"15510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Matthew","family":"Zammit","sequence":"first","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-5225","authenticated-orcid":false,"given":"Chien-Min","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah J.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Ming","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathanial","family":"Holderman","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eve","family":"Tanios","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1116-0280","authenticated-orcid":false,"given":"Mohammed","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Freifelder","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kucharski","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"},{"name":"Fermi National Accelerator Laboratory, Batavia, IL 60510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2167-1391","authenticated-orcid":false,"given":"William N.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA"},{"name":"Marine Biological Laboratory, Woods Hole, MA 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jogeshwar","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2508-8726","authenticated-orcid":false,"given":"Chin-Tu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","unstructured":"(2023, September 04). 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