{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:31:35Z","timestamp":1790811095008,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T00:00:00Z","timestamp":1332201600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Contrast Media &amp; Molecular"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Nanobodies show favourable pharmacokinetic characteristics for tumor targeting, including high tumor\u2010to\u2010background\u2010ratios. Labelled with a therapeutic radionuclide, nanobodies could be used as an adjuvant treatment option for HER2\u2010overexpressing minimal residual disease. The therapeutic radionuclide Lutetium\u2010177 is linked to the nanobody using a bifunctional chelator. The choice of the bifunctional chelator could affect the in vivo behaviour of the radiolabeled nanobody. Consequently, we compared four different bifunctional chelators \u2010 p\u2010SCN\u2010Bn\u2010DOTA, DOTA\u2010NHS\u2010ester, CHX\u2010A\u201d\u2010DTPA or 1B4M\u2010DTPA \u2010 in order to select the optimal chemical link between Lutetium\u2010177 and a HER2 targeting nanobody.<\/jats:p><jats:p>MS results revealed different degrees of chelator\u2010conjugation. High stability in time was observed, together with nanomolar affinities on HER2\u2010expressing tumor cells. Ex vivo biodistributions as well as SPECT\/micro\u2010CT analyses showed high activities in tumors expressing medium HER2 levels with low background activity except for the kidneys. The 1B4M\u2010DTPA\u2010coupled conjugate was further evaluated in a high HER2\u2010expressing tumor model. Here, tumor uptake values of 5.99\u2009\u00b1\u20090.63, 5.12\u2009\u00b1\u20090.17, 2.83\u2009\u00b1\u20090.36 and 2.47\u2009\u00b1\u20090.38 %IA\/g were obtained at 1, 3, 24 and 48h p.i., which coincided with exceptionally low background values, except for the kidneys, and unprecedented tumor\u2010to\u2010background ratios. No specific binding was observed in a HER2\u2010negative model.<\/jats:p><jats:p>In conclusion, the in\u2010house developed anti\u2010HER2 nanobody 2Rs15dHIS can be successfully labeled with <jats:sup>177<\/jats:sup>Lu using different bifunctional chelators. Both macrocyclic and acyclic chelators show high stability in time. High specific tumor uptake combined with the lowest background uptake was measured using the 1B4M\u2010DTPA\u2010based conjugate. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/cmmi.491","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T13:08:10Z","timestamp":1332248890000},"page":"254-264","source":"Crossref","is-referenced-by-count":80,"title":["Development of <sup>177<\/sup>Lu\u2010nanobodies for radioimmunotherapy of HER2\u2010positive breast cancer: evaluation of different bifunctional chelators"],"prefix":"10.1002","volume":"7","author":[{"given":"Matthias","family":"D'Huyvetter","sequence":"first","affiliation":[{"name":"Radiobiology Unit, Molecular and Cellular Biology Expert Group Belgian Nuclear Research Center (SCK\u2022CEN)  Mol Belgium"},{"name":"In vivo Cellular and Molecular Imaging Laboratory Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Aerts","sequence":"additional","affiliation":[{"name":"Radiobiology Unit, Molecular and Cellular Biology Expert Group 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