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The available tracers show several limitations, therefore, the <jats:sup>18<\/jats:sup>F-labelled tracer is in high demand nowadays. The preclinical studies on normal Wistar rats aimed to characterise two potential, novel radiotracers, [<jats:sup>18<\/jats:sup>F]SYN1 and [<jats:sup>18<\/jats:sup>F]SYN2, to evaluate which is a better candidate for PET MPI cardiotracer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The dynamic microPET images showed rapid myocardial uptake for both tracers. However, the uptake was higher and also stable for [<jats:sup>18<\/jats:sup>F]SYN2, with an average standardized uptake value of 3.8. The biodistribution studies confirmed that [<jats:sup>18<\/jats:sup>F]SYN2 uptake in the cardiac muscle was high and stable (3.02%ID\/g at 15\u00a0min and 2.79%ID\/g at 6\u00a0h) compared to [<jats:sup>18<\/jats:sup>F]SYN1 (1.84%ID\/g at 15\u00a0min and 0.32%ID\/g at 6\u00a0h). The critical organs determined in dosimetry studies were the small intestine and the kidneys. The estimated effective dose for humans was 0.00714 mSv\/MBq for [<jats:sup>18<\/jats:sup>F]SYN1 and 0.0109 mSv\/MBq for [<jats:sup>18<\/jats:sup>F]SYN2. The tested dose level of 2\u00a0mg\/kg was considered to be the No Observed Adverse Effect Level (NOAEL) for both candidates. The better results were achieved for [<jats:sup>18<\/jats:sup>F]SYN2, therefore, further preclinical studies were conducted only for this tracer. Radioligand binding assays showed significant responses in 3 from 68 assays: muscarinic acetylcholine M<jats:sub>1<\/jats:sub> and M<jats:sub>2<\/jats:sub> receptors and potassium channel hERG. The compound was mostly metabolised via an oxidative N-dealkylation, while the fluor substituent was not separated from the molecule.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>[<jats:sup>18<\/jats:sup>F]SYN2 showed a favourable pharmacodynamic and pharmacokinetic profile, which enabled a clear visualization of the heart in microPET. The compound was well-tolerated in studies in normal rats with moderate radiation exposure. The results encourage further exploration of [<jats:sup>18<\/jats:sup>F]SYN2 in clinical studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-024-01122-5","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:02:25Z","timestamp":1720447345000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preclinical evaluation of [18F]SYN1 and [18F]SYN2, novel radiotracers for PET myocardial perfusion imaging"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4048-9842","authenticated-orcid":false,"given":"Seweryn","family":"Krajewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Steczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Gotowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Karczmarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Towpik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Witkowska-Patena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"\u0141yczko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Mazur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Przemys\u0142aw","family":"Kozanecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"W\u0142ostowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miros\u0142aw","family":"Dziuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Garnuszek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezary","family":"Kozanecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"1122_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.tcm.2019.02.007","volume":"30","author":"RA Werner","year":"2020","unstructured":"Werner RA, Chen X, Rowe SP, Lapa C, Javadi MS, Higuchi T. 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The animal procedures were approved by Animal Ethics Committees: the microPET and ex vivo biodistribution protocols were approved by the Ist Local Animal Ethics Committee in Warsaw (authorization 069\/2016, approval date 15 June 2016, with further changes 445\/2017 and authorization 400\/2017, approval date 21 November 2017, respectively), the toxicity studies were approved by Local Animal Ethical Committee in Katowice, Poland (authorizations 45\/2018 and 107\/2018, approval dates 16 May and 16 November 2018) and pharmacokinetic profile with SYN2 was carried out based on authorization no. PROEX 211\/10 (approval date 12.09.2019) issued by Spanish General Director of Agriculture, Livestock and Food. The study was carried out in compliance with the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"No human participants or human data was involved in the study. Hepatocytes of human (50-donor, Lot no. HQE, X008005), dog (Male Beagle dog, Lot no. UXH, M00205) and rat (Male Wistar rat, Lot no. ATI, M00025) were purchased from BioreclamationIVT (Brussels, Belgium).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J.K. and M.D. are advisors and received the consultant honoraria from Synektik SA. The other authors have no relevant financial or non-financial interests to disclose.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"63"}}