{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:48:33Z","timestamp":1791157713981,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1630,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>Trastuzumab (Herceptin\u00ae) is a recombinant humanised IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), used for metastatic breast cancer treatment. Radiolabelled trastuzumab may have several future applications for diagnostic use. The aim of the present study was to develop clinical grade <jats:sup>111<\/jats:sup>Indium (<jats:sup>111<\/jats:sup>In) radiolabelled trastuzumab, to evaluate the stability and immunoreactivity of the tracer and to perform a biodistribution study in human tumour\u2010bearing mice. Trastuzumab was radiolabelled with <jats:sup>111<\/jats:sup>In using DTPA as a chelator. <jats:sup>111<\/jats:sup>In\u2010DTPA\u2010trastuzumab (labelling yield 92.3\u00b12.3%, radiochemical purity 97.0\u00b11.5%) is stable in PBS when stored at 4\u00b0C for more than 14 days. The immunoreactive fraction determined by cell\u2010binding assays, using the HER2\u2010overexpressing human ovarian SK\u2010OV\u20103 tumour cell line, was 0.87\u00b10.06. Biodistribution and tumour targeting were studied in HER2 receptor\u2010positive and \u2010negative tumour\u2010bearing athymic mice. The HER2\u2010positive tumour showed (9.77\u00b11.14% injected dose per gram (ID g<jats:sup>\u22121<\/jats:sup>)) substantial uptake of the labelled antibody already after 5 h. The difference in uptake between HER2\u2010positive <jats:italic>versus<\/jats:italic> \u2010negative tumours was even more pronounced 3 days after injection (16.30\u00b10.64% ID g<jats:sup>\u22121<\/jats:sup>), and was visualised by radioimmunoscintigraphy. Liver, spleen and kidney showed marked tracer uptake. In summary, trastuzumab can be efficiently radiolabelled with <jats:sup>111<\/jats:sup>In with high labelling yields and high stability. <jats:sup>111<\/jats:sup>In\u2010DTPA\u2010trastuzumab selectively binds to the human HER2 receptor both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> in animals. Therefore, <jats:sup>111<\/jats:sup>In\u2010DTPA\u2010trastuzumab appears suitable for clinical use.<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 99\u2013106. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705915\">10.1038\/sj.bjp.0705915<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705915","type":"journal-article","created":{"date-parts":[[2004,9,2]],"date-time":"2004-09-02T20:31:48Z","timestamp":1094157108000},"page":"99-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["Preclinical characterisation of <sup>111<\/sup>In\u2010DTPA\u2010trastuzumab"],"prefix":"10.1111","volume":"143","author":[{"given":"Marjolijn N","family":"Lub\u2010de Hooge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos G W","family":"Kosterink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J","family":"Perik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Nijnuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ly","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Bart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert J H","family":"Suurmeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter L","family":"Jager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth G E","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200109273451312"},{"key":"e_1_2_7_3_1","first-page":"2356","article-title":"Circulating HER2 extracellular domain and resistance to chemotherapy in advanced breast cancer","volume":"6","author":"COLOMER R.","year":"2000","journal-title":"Clin. 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