Exploration and Validation of Tumor Targets to Verify Application of Therapeutic Radioisotopes for Radioimmunotherapy

Recently, in the field of nuclear medicine, research on radioimmunotherapy (RIT) is being actively conducted. RIT uses a radioisotope as a marker to administer an antibody that specifically reacts with a tumor-targeting antigen to the patient to identify the tumor site, and radiotherapy is performed to that area. Epidermal growth factor receptor (EGFR) is a key biomarker used for cancer diagnostics and therapy in non-small cell lung cancer (NSCLC). Genetic mutation of the EGFR occurs in approximately 40-55% of patients with NSCLC in East Asians [1,2]. Cetuximab is a recombinant chimeric anti-EGFR IgG1 monoclonal antibody that competitively binds to the EGFR extracellular domain and blocks receptor activation by growth factor [3]. It has been investigated in advanced colorectal cancer, EGFR-expressing NSCLC, and unresectable squamous cell skin cancer [4]. Tumor suppression and therapeutic effects using therapeutic isotopes have been proven through various studies, and it is well-known that therapeutic isotopes are useful for cancer treatment. However, the exact mechanism of action of cancer treatment by therapeutic radioisotopes on the molecular level has not yet been elucidated. In this study, we observe the synergistic effect of cancer treatment as well as changes in the mechanism of action on the molecular level by conjugated with therapeutic radioisotopes to Cetuximab, a well-studied and well-known EGFR tumor-targeting antibody. Therefore, it could be used as basic data for the development of various therapeutic radioisotopes in the future by specifically identifying the molecular mechanism of known radioimmunotherapy drugs.