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In vitro characterization of (177)Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

Forrer, Flavio and Chen, Jianhua and Fani, Melpomeni and Powell, Pia and Lohri, Andreas and Müller-Brand, Jan and Moldenhauer, Gerhard and Maecke, Helmut R.. (2009) In vitro characterization of (177)Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study. European journal of nuclear medicine and molecular imaging, Vol. 36. pp. 1443-1452.

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Official URL: http://edoc.unibas.ch/dok/A6003009

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Abstract

PURPOSE: (131)I- and (90)Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (>20 min) with either (177)Lu or (90)Y. MATERIALS AND METHODS: Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. RESULTS: The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10(5) times excess of diethylenetriaminepentaacetic acid (DTPA, 37 degrees C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m(2) body surface (177)Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of (177)Lu-DOTA-rituximab was tolerated well. CONCLUSION: Our results show that DOTA-rituximab (4:1) can be labelled with (177)Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. (177)Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Radiologie USB > Nuklearmedizin (Wild)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Radiologie USB > Nuklearmedizin (Wild)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Allgemeine innere Medizin Liestal (Zimmerli)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Allgemeine innere Medizin Liestal (Zimmerli)
UniBasel Contributors:Lohri, Andreas N. and Forrer, Flavio
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0340-6997
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:22
Deposited On:24 May 2013 09:04

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