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 Y-90 for radioimmunotherapy (RIT) is targetted. Cetuximab was successively labeled with [Y-90] 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). Y-90 chloride was obtained by Sr-90/Y-90 generator. Radiolabeling was completed in 2 h by the addition of DOTA-cetuximab conjugate at 42 degrees 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 degrees 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 Y-90-DOTA-cetuximab is a potential compound for the treatment of EGFR-expressing cancers.