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Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

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Abstract

Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 × 1013 n cm−2 s−1) of natural Lu2O3 sample with a specific activity of 2.6–3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 °C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-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 pre-coated with DOTA-NHS (0.01–0.1 mg) at 25 °C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 °C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported.

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Acknowledgements

Authors wish to thank Tehran reactor operation team and Dr. M. A. Rowshanzamir for editorial corrections.

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Authors and Affiliations

  1. Radiopharmaceutical Research & Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), 14395-836, Tehran, Iran

    Hassan Yousefnia, Amir Reza Jalilian, Ali Bahrami-Samani, Simindokht Shirvani-Arani & Mohammad Ghannadi-Maragheh

  2. Islamic Azad University, Science and Research Branch, P.O. Box 14155-775, 1477893855, Tehran, Iran

    Edalat Radfar & Azim Arbabi

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  1. Hassan Yousefnia
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  2. Edalat Radfar
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Correspondence to Amir Reza Jalilian.

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Yousefnia, H., Radfar, E., Jalilian, A.R. et al. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy. J Radioanal Nucl Chem 287, 199–209 (2011). https://doi.org/10.1007/s10967-010-0676-4

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