title: Radiolabeled novel mAb 4G1 for immunoSPECT imaging of EGFRvIII expression in preclinical glioblastoma xenografts.
abstract: Epidermal growth factor receptor mutant III (EGFRvIII) is exclusively expressed in tumors, such as glioblastoma, breast cancer and hepatocellular carcinoma, but never in normal organs. Increasing evidence suggests that EGFRvIII has clinical significance in glioblastoma prognosis due to its enhanced tumorigenicity and chemo/radio resistance, thus the development of an imaging approach to early detect EGFRvIII expression with high specificity is urgently needed. To illustrate this point, we developed a novel anti-EGFRvIII monoclonal antibody 4G1 through mouse immunization, cell fusion and hybridoma screening and then confirmed its specificity and affinity by a serial of assays. Following biodistribution and small animal single-photon emission computed tomography (SPECT/CT) imaging of 125I-4G1 in EGFRvIII positive/negative tumor-bearing mice were performed and evaluated to verify the tumor accumulation of this radiotracer. The biodistribution indicated that 125I-4G1 showed prominent tumor accumulation at 24 h post-injection, which reached maximums of 11.20 ± 0.75% ID/g and 13.98 ± 0.57% ID/g in F98npEGFRvIII and U87vIII xenografts, respectively. In contrast, 125I-4G1 had lower tumor accumulation in F98npEGFR and U87MG xenografts. Small animal SPECT/CT imaging revealed that 125I-4G1 had a higher tumor uptake in EGFRvIII-positive tumors than that in EGFRvIII-negative tumors. This study demonstrates that radiolabeled 4G1 can serve as a valid probe for the imaging of EGFRvIII expression, and would be valuable into the clinical translation for the diagnosis, prognosis, guiding therapy, and therapeutic efficacy evaluation of tumors.
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.|Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: Dong
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.|Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009154:Mutation; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors
keywords: EGFRvIII; SPECT imaging; monoclonal antibody; specificity; tumor