{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:55:31Z","timestamp":1789646131744,"version":"4.0.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"JST FOREST Program","doi-asserted-by":"publisher","award":["JPMJFR2116"],"award-info":[{"award-number":["JPMJFR2116"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"JST FOREST Program","doi-asserted-by":"publisher","award":["JP22H03031"],"award-info":[{"award-number":["JP22H03031"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JPMJFR2116"],"award-info":[{"award-number":["JPMJFR2116"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP22H03031"],"award-info":[{"award-number":["JP22H03031"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceutical that targets the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ may be a promising method for increasing tumor delivery by reducing liver uptake. In this study, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptakes using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis of these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake, and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.<\/jats:p>","DOI":"10.3390\/ph17070820","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T12:27:33Z","timestamp":1718972853000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["64Cu2+ Complexes of Tripodal Amine Ligands\u2019 In Vivo Tumor and Liver Uptakes and Intracellular Cu Distribution in the Extrahepatic Bile Duct Carcinoma Cell Line TFK-1: A Basic Comparative Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4244-8914","authenticated-orcid":false,"given":"Mitsuhiro","family":"Shinada","sequence":"first","affiliation":[{"name":"Faculty of Science, Toho University, Funabashi 274-8510, Japan"},{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"},{"name":"Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Faculty of Science, Toho University, Funabashi 274-8510, Japan"},{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"},{"name":"Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4044-0281","authenticated-orcid":false,"given":"Hiroki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"},{"name":"Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukiko","family":"Hihara","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Faculty of Science, Toho University, Funabashi 274-8510, Japan"},{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Higashi","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukie","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan"},{"name":"Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Doi","sequence":"additional","affiliation":[{"name":"Faculty of Science, Toho University, Funabashi 274-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lelievre, P., Sancey, L., Coll, J.L., Deniaud, A., and Busser, B. 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