{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:02:48Z","timestamp":1777575768656,"version":"3.51.4"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Minzasolmin (UCB0599) is an orally administered, small molecule inhibitor of ASYN misfolding in development as a potential disease-modifying therapy for Parkinson\u2019s disease. Here we describe the preclinical development of a radiolabeled tracer and results from a phase 1 study using the tracer to investigate the brain distribution of minzasolmin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Procedures<\/jats:title>\n                <jats:p>In the preclinical study, two radiolabeling positions were investigated on the <jats:italic>S<\/jats:italic>-enantiomer of minzasolmin (UCB2713): [<jats:sup>11<\/jats:sup>C]methylamine UCB2713 ([<jats:sup>11<\/jats:sup>C-<jats:italic>N<\/jats:italic>-CH<jats:sub>3<\/jats:sub>]UCB2713) and [<jats:sup>11<\/jats:sup>C]carbonyl UCB2713 ([<jats:sup>11<\/jats:sup>C-CO]UCB2713). Male C57 black 6 mice (<jats:italic>N<\/jats:italic>\u2009=\u200910) received intravenous [<jats:sup>11<\/jats:sup>C-<jats:italic>N<\/jats:italic>-CH<jats:sub>3<\/jats:sub>]UCB2713; brain homogenates were assessed for radioactivity and plasma samples analyzed by high-performance liquid chromatography. Positron emission tomography-computed tomography (PET-CT) was used to image brains in a subset of mice (<jats:italic>n<\/jats:italic>\u2009=\u20093). In the open-label, phase 1 study, healthy volunteers were scanned twice with PET-CT following injection with [<jats:sup>11<\/jats:sup>C]minzasolmin radiotracer (\u2264\u200910\u00a0\u00b5g), first without, then with oral dosing with non-radiolabeled minzasolmin 360\u00a0mg. Primary objective: to determine biodistribution of minzasolmin in the human brain; secondary objectives included minzasolmin safety\/tolerability.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Preclinical data supported the use of [<jats:sup>11<\/jats:sup>C]minzasolmin in clinical studies. In the phase 1 study, PET data showed substantial drug signal in the brain of healthy volunteers (<jats:italic>N<\/jats:italic>\u2009=\u2009<jats:italic>4<\/jats:italic>). The mean estimated whole brain total distribution volume (V<jats:sub>T<\/jats:sub>) at equilibrium across all regions of interest was 0.512\u00a0mL\/cm<jats:sup>3<\/jats:sup>, no difference in V<jats:sub>T<\/jats:sub> was observed following administration of minzasolmin 360\u00a0mg. Treatment-emergent adverse events (TEAEs) were reported by 75% (<jats:italic>n<\/jats:italic>\u2009=\u20093) of participants. No drug-related TEAEs, deaths, serious adverse events, or discontinuations were reported.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Following positive preclinical results with the N-methyl labeled PET tracer, [<jats:sup>11<\/jats:sup>C]minzasolmin was used in the phase 1 study, which demonstrated that minzasolmin readily crossed the blood\u2013brain barrier and was well distributed throughout the brain. Safety and pharmacokinetic findings were consistent with previous early-phase studies (such as UP0077, NCT04875962).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11307-023-01878-7","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T19:03:00Z","timestamp":1702926180000},"page":"310-321","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation and Application of a PET Tracer in Preclinical and Phase 1 Studies to Determine the Brain Biodistribution of Minzasolmin (UCB0599)"],"prefix":"10.1007","volume":"26","author":[{"given":"Jo\u00ebl","family":"Mercier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Bani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anny-Odile","family":"Colson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Germani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Lalla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Plisson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mickael","family":"Huiban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Searle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois-Xavier","family":"Mathy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Nicholl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Otoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan Willem","family":"Smit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanja","family":"van Asch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Wagneur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-6622","authenticated-orcid":false,"given":"Ralph Paul","family":"Maguire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"1878_CR1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1136\/jnnp-2019-322338","volume":"91","author":"J Jankovic","year":"2020","unstructured":"Jankovic J, Tan EK (2020) Parkinson\u2019s disease: etiopathogenesis and treatment. 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MB, ML, MG, JWS, and CO were employees of UCB Pharma at the time this work was conducted and may hold or have access to stock options. CP, MH, and GS are all employees of Invicro. VVA is an independent consultant.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All applicable institutional and\/or national guidelines for the care and use of animals were followed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}