{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T02:00:53Z","timestamp":1760061653667},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":2757,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[1998,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Much effort has been expended in the search for hepatocyte\u2010specific MR contrast agents to improve the detection and characterization of liver tumors. The purpose of this study was to establish human hepatocyte cell cultures to preclinically assess hepatocytetargeted magnetopharmaceuticals. Cultured human hepatocytes were sandwiched between two layers of collagen preserving both hepatocyte function and morphology over prolonged period of time. Cultures (<jats:italic>n<\/jats:italic> = 37) were subsequently used to test different fluorescinated MR contrast agents. Plain and rhodaminated monocrystalline iron oxide particles (MION and MION\u2010rh) and asialoglycoprotein\u2010receptor\u2010specific rhodaminated asialofetuin coupled to MION (MION\u2010ASF\u2010rh) were prepared. Competition experiments of these agents were performed with D(+)\u2010galactose to study the specificity of galactose\u2010mediated cell uptake. To assess the impact of cell integrity on cell uptake, functional experiments with CCI<jats:sub>4<\/jats:sub> were performed. Normal cell cultures showed significantly higher fluorescence light emission after incubation with hepatocyte\u2010di\u2010rected ASF\u2010MION\u2010rh than after incubation with MION\u2010rh. Competition experiments of ASF\u2010MION\u2010rh with galactose showed a dose\u2010dependent decrease of calibrated fluorescence light emission. Cell cultures treated with CCI<jats:sub>4<\/jats:sub> demonstrated a dose\u2010dependent significant reduction of calibrated fluorescence light emission, indicating reduced uptake of ASF\u2010MION\u2010rh. Our data demonstrate that stable human hepatocyte cell cultures can be used to preclinically assess novel magnetopharmaceuticals. Different contrast agents may be directly compared to each other and may accelerate their preclinical design. Because the assay can be applied to cells from any species, it may represent an ideal test system before clinical trials of new cell\u2010directed MR contrast agents.<\/jats:p>","DOI":"10.1002\/jmri.1880080326","type":"journal-article","created":{"date-parts":[[2007,3,16]],"date-time":"2007-03-16T14:09:43Z","timestamp":1174054183000},"page":"687-689","source":"Crossref","is-referenced-by-count":8,"title":["Preclinical assessment of hepatocyte\u2010targeted MR contrast agents in stable human liver cell cultures"],"prefix":"10.1002","volume":"8","author":[{"given":"Peter","family":"Reimer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augustinus","family":"Bader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Weissleder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.185.1.1523301"},{"key":"e_1_2_1_3_2","first-page":"83","volume-title":"Developments in contrast agent research","author":"Cavagna F","year":"1991"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0730-725X(90)90143-P"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.155.6.2122660"},{"key":"e_1_2_1_6_2","first-page":"165","article-title":"Ultrastructural analysis of asialoglycoprotein receptor mediated endocytosis in cultured newborn hepatocytes","volume":"37","author":"Dini L","year":"1991","journal-title":"Cell Mol Biol"},{"key":"e_1_2_1_7_2","first-page":"S185","article-title":"Receptor mediated endocytosis in matrix overlaid primary rat hepatocytes","volume":"14","author":"Bader A","year":"1995","journal-title":"J Exp Clin Cancer Res"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0730-725X(95)00053-J"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910290504"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0730-725X(93)90074-N"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61797-5"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02623304"},{"key":"e_1_2_1_13_2","first-page":"175","article-title":"Hepatocyte function and extracellular matrix geometry: long\u2010term culture in a sandwich configuration","volume":"3","author":"Dunn JCY","year":"1989","journal-title":"FASEB J"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00389966"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840030118"},{"key":"e_1_2_1_16_2","volume-title":"Statistical methods in medical research","author":"Armitage P","year":"1987"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.182.2.1732982"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/bp00015a007"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bp00009a007"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.178.3.1994416"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmri.1880080326","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.1880080326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T14:07:05Z","timestamp":1698502025000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.1880080326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,5]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1998,5]]}},"alternative-id":["10.1002\/jmri.1880080326"],"URL":"https:\/\/doi.org\/10.1002\/jmri.1880080326","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,5]]}}}