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

Abstract

INTRODUCTION:

ROBO1 is a membrane protein that contributes to tumor metastasis and angiogenesis. We previously reported that 90Y-labeled anti-ROBO1 monoclonal antibody (90Y-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, 111In-labeled anti-ROBO1 monoclonal antibody (111In-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 90Y-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 111In-anti-ROBO1 IgG. The liver, kidney, spleen, and lung showed comparably high accumulation of 111In-labeled anti-ROBO1. In the RIT study, 90Y-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 90Y-anti-ROBO1 IgG is a promising treatment for ROBO1-positive SCLC.

• Authors: Kentaro Fujiwara, Keitaro Koyama, Kosuke Suga, Masako Ikemura, Yasutaka Saito, Akihiro Hino, Hiroko Iwanari, Osamu Kusano-Arai, Kenichi Mitsui, Hiroyuki Kasahara, Masashi Fukayama, Tatsuhiko Kodama, Takao Hamakubo, Toshimitsu Momose
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0125468 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26017283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Nerve Tissue Proteins
• Receptors, Immunologic
• Yttrium Radioisotopes
• roundabout protein

Topics

• Animals
• Antibodies, Monoclonal (chemistry, immunology, pharmacokinetics, pharmacology)
• Humans
• Lung Neoplasms (drug therapy, pathology, radiotherapy)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Nerve Tissue Proteins (immunology, metabolism)
• Radioimmunotherapy (methods)
• Receptors, Immunologic (immunology, metabolism)
• Small Cell Lung Carcinoma (drug therapy, pathology, radiotherapy)
• Tissue Distribution
• Xenograft Model Antitumor Assays (methods)
• Yttrium Radioisotopes (chemistry, pharmacokinetics, therapeutic use)