title: Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor.
abstract: The type III mutant epidermal growth factor receptor (EGFR) is expressed on the cell surface of a subset of glioma, but not of normal tissues. In this study, we investigated the in vivo kinetics of 3C10 mouse monoclonal antibody (mAb), specifically recognizing the type III mutant EGFR (EGFRvIII), using athymic nude mice bearing the intracranial glioma xenograft overexpressing the EGFRvIII. Human glioma cell line, U87MG, expressing the wild type EGFR and the transfectant, named U87MG x deltaEGFR, expressing the EGFRvIII, were transplanted subcutaneously or intracranially to nude mice. 3C10 mAb labeled with a technetium-99m (99mTc) was intravenously injected into these nude mice and then the mice were sacrificed at 24 h later, and the 99mTc-uptake by xenografts and major normal organs was measured to determine the biodistribution of mAb. Furthermore, at 3, 6 and 24 h after injection of 99mTc-labeled 3C10 mAb, whole-body scintigraphy was obtained with a gamma camera to localize the tumor site. 3C10 mAb significantly accumulated to U87MG x deltaEGFR xenografts transplanted subcutaneously or intracranially in nude mice, showing high tumor-to-blood ratio of 10.30 and 4.01, respectively. In contrast, uptake of control antibody in the intracranial tumor was as low as 0.43. In scintigrams, intracranially transplanted U87MG x deltaEGFR xenografts were detectable at 3 h after injection of 99mTc-labeled 3C10 mAb. These results suggest that intravenously injected 3C10 mAb specifically accumulated to the subcutaneous or intracranial glioma xenograft expressing the EGFRvIII and 3C10 mAb is a potential diagnostic and therapeutic agent for patients with gliomas expressing the EGFRvIII.
authors.affiliation: Department of Neurosurgery, Division of Immunology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. syuntaro@naa.att.ne.jp
authors.forename: Syuntaro
authors.initials: S
authors.lastname: Takasu
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takahashi
authors.forename: Sho
authors.initials: S
authors.lastname: Okamoto
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Nakayashiki
authors.forename: Kenta
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Norimoto
authors.initials: N
authors.lastname: Nakahara
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kozaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Miyaishi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saga
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging*; D006801:Humans; D018796:Immunoconjugates; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics*; D016719:Radioimmunodetection; D011877:Radionuclide Imaging; D013667:Technetium; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; C410723:epidermal growth factor receptor VIII; D013667:Technetium; D066246:ErbB Receptors