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01.09.2009 | Original Article | Ausgabe 9/2009

European Journal of Nuclear Medicine and Molecular Imaging 9/2009

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

Zeitschrift:
European Journal of Nuclear Medicine and Molecular Imaging > Ausgabe 9/2009
Autoren:
Flavio Forrer, Jianhua Chen, Melpomeni Fani, Pia Powell, Andreas Lohri, Jan Müller-Brand, Gerhard Moldenhauer, Helmut R. Maecke
Wichtige Hinweise
Flavio Forrer and Jianhua Chen contributed equally to this work.

Abstract

Purpose

131I- and 90Y-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 177Lu or 90Y.

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 105 times excess of diethylenetriaminepentaacetic acid (DTPA, 37°C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m2 body surface 177Lu-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 177Lu-DOTA-rituximab was tolerated well.

Conclusion

Our results show that DOTA-rituximab (4:1) can be labelled with 177Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 177Lu-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.

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