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Imaging microglia with radiotracers developed for use with positron emission tomography (PET) allows researchers to study these cells in their native tissue microenvironment. However, many relevant microglial imaging targets such as the 18\u00a0kDa translocator protein are also expressed on non-microglial cells, which can complicate the interpretation of PET findings. <jats:sup>11<\/jats:sup>C-CPPC was developed to image the macrophage colony-stimulating factor 1 receptor, a target that is expressed largely by microglia relative to other cell types in the brain. Our prior work with <jats:sup>11<\/jats:sup>C-CPPC demonstrated its high, specific uptake in brains of rodents and nonhuman primates with neuroinflammation, which supports the current first-in-human evaluation of its pharmacokinetic behavior in the brains of healthy individuals.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eight healthy nonsmoker adults completed a 90-min dynamic PET scan that began with bolus injection of <jats:sup>11<\/jats:sup>C-CPPC. Arterial blood sampling was collected in order to generate a metabolite-corrected arterial input function. Tissue time-activity curves (TACs) were generated using regions of interest identified from co-registered magnetic resonance imaging data. One- and two-tissue compartmental models (1TCM and 2TCM) as well as Logan graphical analysis were compared.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Cortical and subcortical tissue TACs peaked by 37.5\u00a0min post-injection of <jats:sup>11<\/jats:sup>C-CPPC and then declined. The 1TCM was preferred. Total distribution volume (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>) values computed from 1TCM aligned well with those from Logan graphical analysis (<jats:italic>t<\/jats:italic>*\u2009=\u200930), with <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> values relatively high in thalamus, striatum, and most cortical regions, and with relatively lower <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> in hippocampus, total white matter, and cerebellar cortex.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results extend support for the use of <jats:sup>11<\/jats:sup>C-CPPC with PET to study microglia in the human brain.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-022-00929-4","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T23:04:02Z","timestamp":1664492642000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["First-in-human use of 11C-CPPC with positron emission tomography for imaging the macrophage colony-stimulating factor 1 receptor"],"prefix":"10.1186","volume":"12","author":[{"given":"Jennifer M.","family":"Coughlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech G.","family":"Lesniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney K.","family":"Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Katherine","family":"Brosnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley","family":"O\u2019Toole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Zandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon Eileen","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunkou","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Dannals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilja","family":"Solnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Horti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-3010","authenticated-orcid":false,"given":"Martin G.","family":"Pomper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"issue":"11","key":"929_CR1","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/s1474-4422(20)30346-x","volume":"19","author":"WC Kreisl","year":"2020","unstructured":"Kreisl WC, Kim MJ, Coughlin JM, Henter ID, Owen DR, Innis RB. 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This article does not contain any studies involving animals. The study was approved by the Johns Hopkins Investigational Review Board and Radiation Safety Committees. All subjects provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Under a license agreement between D&D Pharmatech and the Johns Hopkins University, the University, AGH, and MGP are entitled to royalty distributions related to the technology described in the study. MGP is a founder of and holds equity in D&D Pharmatech. He also is a paid consultant to the company. AGH is a paid consultant to the company. As the spouse of MGP, JMC shares his disclosures. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"64"}}