title: 90Y-Labeled Anti-ROBO1 Monoclonal Antibody Exhibits Antitumor Activity against Small Cell Lung Cancer Xenografts.
abstract: BACKGROUND
  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.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Koyama
authors.affiliation: SANKYO LABO SERVICE Co., Ltd., Edogawaku, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Suga
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Ikemura
authors.affiliation: FUJIFILM RI Pharma Co., Ltd., SAMMU-CITY, CHIBA, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Saito
authors.affiliation: FUJIFILM RI Pharma Co., Ltd., SAMMU-CITY, CHIBA, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hino
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kusano-Arai
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mitsui
authors.affiliation: FUJIFILM RI Pharma Co., Ltd., SAMMU-CITY, CHIBA, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kasahara
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.affiliation: Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Momose
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D016499:Radioimmunotherapy / Q000379:methods; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D015021:Yttrium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000097905:Roundabout Proteins
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D015021:Yttrium Radioisotopes; D000097905:Roundabout Proteins