{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T04:19:11Z","timestamp":1754108351076},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,1,16]],"date-time":"2006-01-16T00:00:00Z","timestamp":1137369600000},"content-version":"vor","delay-in-days":4339,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[1994,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The tumour uptake as well as the anti\u2010tumour activity of RS\u20101541 (palmitoyl rhizoxin), a potent antineoplastic agent, were investigated in mice bearing M5076 sarcoma. After intravenous administration, <jats:sup>14<\/jats:sup>C\u2010RS\u20101541 preferentially bound to the lipoproteins, to which <jats:sup>14<\/jats:sup>C\u2010rhizoxin did not bind. <jats:sup>14<\/jats:sup>C\u2010RS\u20101541 showed persisting high concentrations of radioactivity in the plasma (<jats:italic>T<\/jats:italic><jats:sub>1\/2\u03b1<\/jats:sub>, 4\u00b79 h). The uptake of radioactivity by the tumour was second to those by the liver and spleen, and several times greater than those by the other tissues. Selective and sustained uptake by the tumour was also demonstrated by wholebody autoradiography. A considerable amount of rhizoxin was detected only in the tumour after administration of <jats:sup>14<\/jats:sup>C\u2010RS\u20101541, and the area under the tissue\u2010concentration\u2010time curve (AUC<jats:sub>t<\/jats:sub>) and the mean residence time (MRT) of rhizoxin in the tumour were much higher than those after administration of <jats:sup>14<\/jats:sup>C\u2010rhizoxin itself. The rhizoxin formation in the tumour was significantly reduced by chloroquine, a lysosomal enzyme inhibitor. RS\u20101541 showed a higher therapeutic activity than rhizoxin. At a 4 mg kg<jats:sup>\u22121<\/jats:sup> dose, the maximum growth inhibition was 92% for RS\u20101541 and 41% for rhizoxin. These results indicate that RS\u20101541, but not rhizoxin, is taken up by the tumour via endocytosis, most likely via the low\u2010density\u2010lipoprotein receptor, after binding to lipoproteins. Thus, RS\u20101541 was considered to exhibit sustained high concentration in tumours and potent anti\u2010tumour activity.<\/jats:p>","DOI":"10.1002\/bdd.2510150202","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T09:35:40Z","timestamp":1160818540000},"page":"93-107","source":"Crossref","is-referenced-by-count":6,"title":["Contribution of serum lipoproteins as carriers of antitumour agent RS\u20101541 (palmitoyl rhizoxin) in mice"],"prefix":"10.1002","volume":"15","author":[{"given":"T.","family":"Tokui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Kuroiwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Tokui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Sasagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Komai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.3186\/jjphytopath.46.40"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(87)90206-6"},{"key":"e_1_2_1_4_2","first-page":"381","volume":"46","author":"Tsuruo T.","year":"1986","journal-title":"Cancer Res."},{"key":"e_1_2_1_5_2","unstructured":"D. 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