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Development of 153Sm-DTPA-rituximab for radioimmunotherapy

Bahrami-Samani A., Ghannadi-Maragheh M., Jalilian A. R., Yousefnia H., Garousi J., Moradkhani S.

Nukleonika

2009

Vol. 54, No. 4

271-277

Combining beta-particle effect with therapeutic properties of anti-CD20 monoclonal antibody in lymphomas, Mabthera™ (rituximab) was targeted in this study. The antibody was labeled with 153Sm-samarium chloride (185 MBq) after conjugation with freshly prepared ccDTPA. Conjugated-rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH = 7.8) to a glass tube precoated with freshly prepared ccDTPA (0.01–0.1 mg) at 25 degrees centigrade. Sm-153 chloride was obtained by a thermal neutron flux (5 × 1013 nźcm–2źs–1) of an enriched 152Sm2O3 sample, dissolved in acidic media. Radiolabeling was performed in one hour by the addition of DTPA-rituximab conjugate at room temperature. Radiochemical purity of 96% (ITLC) and 98% (HPLC) were obtained for the final radioimmunoconjugate (specific activity = 120 TBq/mmol). The final isotonic 153Sm-rituximab complex was checked by gel electrophoresis for protein integrity retention. Biodistribution studies in normal rats were performed to determine radioimmunoconjugate distribution up to 24 h. SPECT images were also obtained using 103 keV photons up to 48 h.