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Previous evaluation of [<jats:sup>18<\/jats:sup>F]JHU94620 for the non-invasive assessment of the CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, and generation of brain-penetrating radiometabolites have been its main limitations. To reduce the bias of CB2R quantification by blood\u2013brain barrier (BBB)-penetrating radiometabolites, we aimed to improve the metabolic stability by developing -<jats:italic>d<\/jats:italic><jats:sub>4<\/jats:sub> and -<jats:italic>d<\/jats:italic><jats:sub>8<\/jats:sub> deuterated isotopologues of [<jats:sup>18<\/jats:sup>F]JHU94620.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The deuterated [<jats:sup>18<\/jats:sup>F]JHU94620 isotopologues showed improved metabolic stability avoiding the accumulation of BBB-penetrating radiometabolites in the brain over time. CB2R-specific binding with <jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub> values in the low nanomolar range was determined across species. Dynamic PET studies revealed a CB2R-specific and reversible uptake of [<jats:sup>18<\/jats:sup>F]JHU94620-<jats:italic>d<\/jats:italic><jats:sub>8<\/jats:sub> in the spleen and to a local <jats:italic>h<\/jats:italic>CB2R(D80N) protein overexpression in the striatal region in rats.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These results support further investigations of [<jats:sup>18<\/jats:sup>F]JHU94620-<jats:italic>d<\/jats:italic><jats:sub>8<\/jats:sub> in pathological models and tissues with a CB2R overexpression as a prerequisite for clinical translation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s41181-024-00319-2","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T12:18:27Z","timestamp":1734956307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and evaluation of deuterated [18F]JHU94620 isotopologues for the non-invasive assessment of the cannabinoid type 2 receptor in brain"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2325","authenticated-orcid":false,"given":"Daniel","family":"G\u00fcndel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8213-6715","authenticated-orcid":false,"given":"Mudasir","family":"Maqbool","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-0567","authenticated-orcid":false,"given":"Rodrigo","family":"Teodoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5171","authenticated-orcid":false,"given":"Friedrich-Alexander","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Heerklotz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-3857","authenticated-orcid":false,"given":"Magali","family":"Toussaint","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther-Conrad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-7190","authenticated-orcid":false,"given":"Guy","family":"Bormans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-7058","authenticated-orcid":false,"given":"Peter","family":"Brust","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-1271","authenticated-orcid":false,"given":"Klaus","family":"Kopka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-7945","authenticated-orcid":false,"given":"Rare\u015f-Petru","family":"Moldovan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"319_CR1","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s11307-013-0626-y","volume":"15","author":"R Ahmad","year":"2013","unstructured":"Ahmad R, Koole M, Evens N, Serdons K, Verbruggen A, Bormans G, et al. 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