期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 36, 期 9, 页码 1443-1452出版社
SPRINGER
DOI: 10.1007/s00259-009-1120-2
关键词
Lu-177-DOTA-rituximab; Non-Hodgkin's lymphoma; Radioimmunotherapy; CD20(+) lymphoma
资金
- Cancer League beider Basel
- Stiftung fur klinische Krebsforschung (J.P. Obrecht Foundation)
I-131- and Y-90-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 Lu-177 or Y-90. 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. 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, 37A degrees C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m(2) body surface Lu-177-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 Lu-177-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with Lu-177 with sufficient stability while the immunoconjugate retains its immunoreactivity. Lu-177-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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