Abstract | INTRODUCTION: 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.
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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)
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Chemical References |
- Antibodies, Monoclonal
- Nerve Tissue Proteins
- Receptors, Immunologic
- Yttrium Radioisotopes
- roundabout protein
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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)
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