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

Research output: Contribution to journalArticlepeer-review

Authors

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

Colleges, School and Institutes

External organisations

  • Nuclear Science and Technology Research Institute (NSTRI)
  • Islamic Azad University, Science and Research Branch

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 Lu 2O3 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.

Bibliographic note

Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

Details

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalJournal of Radioanalytical and Nuclear Chemistry
Volume287
Issue number1
Publication statusPublished - Jan 2011