Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-01

AUTHORS

Hassan Yousefnia, Edalat Radfar, Amir Reza Jalilian, Ali Bahrami-Samani, Simindokht Shirvani-Arani, Azim Arbabi, Mohammad Ghannadi-Maragheh

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. More... »

PAGES

199-209

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10967-010-0676-4

DOI

http://dx.doi.org/10.1007/s10967-010-0676-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024529932


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44 schema:description 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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