title: Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.
abstract: The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.
authors.forename: Ketao
authors.initials: K
authors.lastname: Mu
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Ai
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.forename: Yihao
authors.initials: Y
authors.lastname: Yao
authors.forename: Lingyu
authors.initials: L
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Hongbing
authors.initials: H
authors.lastname: Xiang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D045744:Cell Line, Tumor; D003911:Dextrans / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D058185:Magnetite Nanoparticles; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D003911:Dextrans; D058185:Magnetite Nanoparticles; D066246:ErbB Receptors; C065507:ferumoxides