Production and evaluation of cellular effects of 153Sm-DOTA-cetuximab and 177Lu-DOTA-cetuximab radioconjugates

Abstract

Antibody-based radiopharmaceuticals are of increasing interest today in cancer imaging and radiotherapy. The cetuximab monoclonal antibody binds to the epidermal growth factor receptor (EGFR) and thus provides therapeutic and diagnostic protocols against this receptor. Following purification and conjugation with freshly prepared DOTA-NHS, the cetuximab antibody was labeled with lutetium 177 and samarium chloride-153. Labeling efficiency and in vitro stability were measured using thin-layer chromatography. Cellular tests were performed to determine radioimmunoactivity in cancer cells. The results showed that the labeling efficiencies of 177Lu-DOTA-cetuximab and 153Sm-DOTA-cetuximab were more than 97±1% and 96±2%, respectively. Also, the in vitro stability of the labeled products in fresh human serum after 96 hours was 83± 22% and 78%, respectively. Immunoreactivity was 91% for 177Lu-DOTA-cetuximab and 66±1% for 153Sm-DOTA-cetuximab. With different intensities based on time and beta energy, both products inhibited the growth of HT29 colon cancer cells. The results showed that the immunoconjugate complexes of 177Lu-DOTA-cetuximab and 153Sm-DOTA-cetuximab can be considered a novel radiopharmaceutical for cancer radioimmunotherapy.

Keywords

• cetuximab
• lutetium 177
• samarium153
• radiochemical purity
• cell growth inhibition