{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:28:46Z","timestamp":1792628926695,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Imaging Biol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>Measuring hepatic flux rates of transportable substrates has the potential for assessing liver function. PET imaging of a PET-enabled substrate may provide a more straightforward measurement of time-dependent substrate concentration through the liver than MRI using an MRI contrast agent. Here we synthesized and evaluated the hepatobiliary transport of a new hepatospecific PET agent designed for stable Cu<jats:sup>2+<\/jats:sup> chelation and transport by hepatic OATPs, [<jats:sup>64<\/jats:sup>Cu]Cu-EOB-NOTA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Procedures<\/jats:title>\n            <jats:p>EOB-NOTA was synthesized, its two enantiomers separated by chiral HPLC, and individually radiolabeled with [<jats:sup>64<\/jats:sup>Cu]Cu<jats:sup>2+<\/jats:sup>. Cocktails of each enantiomer of [<jats:sup>64<\/jats:sup>Cu]Cu-EOB-NOTA and Gd-EOB-DTPA were formulated for simultaneous PET\/MRI imaging of hepatic flux by PET and MRI. Two mouse models were evaluated: wild-type mice and mice expressing only human hepatic OATPs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In wild-type mice, [<jats:sup>64<\/jats:sup>Cu]Cu-EOB-NOTA hepatic influx and efflux was high, but slower compared to Gd-EOB-DTPA. Neither enantiomer of [<jats:sup>64<\/jats:sup>Cu]Cu-EOB-NOTA exhibited detectable transport into the liver in mice expressing human OATPs. This was validated by waste clearance studies and <jats:italic>in vitro<\/jats:italic> uptake assays in cells engineered to express rodent and human OATPs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>[<jats:sup>64<\/jats:sup>Cu]Cu-EOB-NOTA exhibited no detectable hepatic uptake by transgenic mice expressing human hepatic transporters. This finding was surprising given the efficient transport of the structurally similar metal chelate Gd-EOB-DTPA, and underscores challenges in the\u00a0design of imaging molecular probes, including poor predictability for hepatic transport, and the value of validating new agents in mice expressing human hepatic transporters.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11307-025-02009-0","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T02:05:20Z","timestamp":1746065120000},"page":"305-312","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Species-Specific Hepatic Uptake of [64Cu]Cu-EOB-NOTA, A Newly Designed Hepatospecific PET Agent"],"prefix":"10.1007","volume":"27","author":[{"given":"Jinda","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijja Janaki","family":"Ramulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane L.","family":"Mallett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Legend E.","family":"Kenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Kauffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapas","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Sabbaghan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyendra","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt R.","family":"Zinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-5781","authenticated-orcid":false,"given":"Erik M.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"6","key":"2009_CR1","doi-asserted-by":"publisher","first-page":"e1007157","DOI":"10.1371\/journal.pcbi.1007157","volume":"15","author":"MF Forsgren","year":"2019","unstructured":"Forsgren MF, Karlsson M, DahlqvistLeinhard O, Dahlstrom N, Noren B, Romu T, Ignatova S, Ekstedt M, Kechagias S, Lundberg P, Cedersund G (2019) Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort. 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