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

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.