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Preparation and quality control and biodistribution studies of [90Y]-DOTA-cetuximab for radioimmunotherapy

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Abstract

Yttrium-90 is a useful radionuclide for radioimmunotherapy (RIT) and the anti-epidermal growth factor receptor (anti-EGFR) antibody cetuximab is clinicsally approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Thus in this work radiolabeling of monoclonal anti-EGFR with 90Y for radioimmunotherapy (RIT) is targetted. Cetuximab was successively labeled with [90Y] chloride (74 MBq) 2 mCi after conjugation with macrocyclics bifunctional chelating agent, 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS), purified and concentrated by centrifugation using an Amicon Ultra-15 filter (Millipore, MWCo, 30000). 90Y chloride was obtained by 90Sr/90Y generator. Radiolabeling was completed in 2 h by the addition of DOTA-cetuximab conjugate at 42 °C. The stability of radiolabeled was studied in human serum. Biodistribution studies in normal rats were carried out to determine the radioimmunoconjugate distribution up to 96 h. Radiochemical purity of 92 % (using ITLC) was obtained for final radioimmunoconjugate (Specific activity = 0.55 GBq/mg). Stability of radiolabeled protein in presence of human serum was tested at 37 °C for up to 24 h. Biodistribution studies demonstrated the highest ID/g % in the blood (2.62 ± 0.005 at 24 h) and the liver (2.19 ± 0.001). This study demonstrated that 90Y-DOTA-cetuximab is a potential compound for the treatment of EGFR-expressing cancers.

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Acknowledgments

The authors wish to thank Mr. Mirfallah and Mr. Mazidi for performing animal tests. We acknowledge the financial support of the National Radiopharmaceutical Production Project, 2009 Granted by Iranian Government.

Disclosure

The authors declare that they have no proprietary, financial, professional or other personal interest in any product, service and/or company that could be construed as influencing the position presented in this article.

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Authors and Affiliations

  1. Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Ariandokht Vakili

  2. Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran

    Amir Reza Jalilian, Kamal Yavari, Simindokht Shirvani-Arani, Alireza Khanchi, Ali Bahrami-Samani & Bahram Salimi

  3. Department of Biomedical Physics and Engineering, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Alireza Khorrami-Moghadam

Authors
  1. Ariandokht Vakili
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  2. Amir Reza Jalilian
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  8. Alireza Khorrami-Moghadam
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Correspondence to Ariandokht Vakili.

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Vakili, A., Jalilian, A.R., Yavari, K. et al. Preparation and quality control and biodistribution studies of [90Y]-DOTA-cetuximab for radioimmunotherapy. J Radioanal Nucl Chem 296, 1287–1294 (2013). https://doi.org/10.1007/s10967-013-2426-x

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  • DOI: https://doi.org/10.1007/s10967-013-2426-x

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