90Y-Labeled Anti-ROBO1 Monoclonal Antibody Exhibits Antitumor Activity against Small Cell Lung Cancer Xenografts

Introduction ROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that Y-90-labeled anti-ROBO1 monoclonal antibody (Y-90-anti-ROBO1 IgG) showed an antitumor effect against ROBO1-positive tumors. In this study, we performed a biodistribution study and radioimmunotherapy (RIT) against ROBO1-positive small cell lung cancer (SCLC) models. Methods For the biodistribution study, In-111-labeled anti-ROBO1 monoclonal antibody (In-111-anti-ROBO1 IgG) was injected into ROBO1-positive SCLC xenograft mice via the tail vein. To evaluate antitumor effects, an RIT study was performed, and SCLC xenograft mice were treated with Y-90-anti-ROBO1 IgG. Tumor volume and body weight were periodically measured throughout the experiments. The tumors and organs of mice were then collected, and a pathological analysis was carried out. Results As a result of the biodistribution study, we observed tumor uptake of In-111-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of In-111-labeled anti-ROBO1. In the RIT study, Y-90-anti-ROBO1 IgG significantly reduced tumor volume compared with baseline. Pathological analyses of tumors revealed coagulation necrosis and fatal degeneration of tumor cells, significant reduction in the number of Ki-67-positive cells, and an increase in the number of apoptotic cells. A transient reduction of hematopoietic cells was observed in the spleen, sternum, and femur. Conclusions These results suggest that RIT with Y-90-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC.