title: Monoclonal antibody conjugated magnetic nanoparticles could target MUC-1-positive cells in vitro but not in vivo.
abstract: MUC1 antigen is recognized as a high-molecular-weight glycoprotein that is unexpectedly over-expressed in human breast and other carcinomas. In contrast, C595 a monoclonal antibody (mAb) against the protein core of the human urinary epithelial machine, is commonly expressed in breast carcinomas. The aim of this study was to conjugate ultra-small super paramagnetic iron oxide nanoparticles (USPIO) with C595 mAb, in order to detect in vivo MUC1 expression. A dual contrast agent (the C595 antibody-conjugated USPIO labeled with 99mTc) was prepared for targeted imaging and therapy of anti-MUC1-expressing cancers. The C595 antibody-conjugated USPIO had good stability and reactivity in the presence of blood plasma at 37 °C. No significant differences were observed in immunoreactivity results between conjugated and nonconjugated nanoparticles. The T1 and T2 measurements show >79 and 29% increments (for 0.02 mg/ml iron concentrations) in T1 and T2 values for USPIO-C595 in comparison with USPIO, respectively. The nanoprobes showed the interesting targeting capability of finding the MUC1-positive cell line in vitro. However, we found disappointing in vivo results (i.e. very low accumulation of nanoprobes in the targeted site while >80% of the injected dose per gram was taken up by the liver and spleen), not only due to the coverage of targeting site by protein corona but also because of absorption of opsonin-based proteins at the surface of nanoprobes.
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shanehsazzadeh
authors.affiliation: Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-Str. 4, D-18119, Rostock, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Gruettner
authors.affiliation: Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Iran.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lahooti
authors.affiliation: Nanotechnology Research Center and Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Experimental Radiation Oncology, School of Medicine, University of Western Sydney, NSW 2217, Australia.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Allen
authors.affiliation: National cell bank, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Ghavami
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
authors.forename: Fariba Johari
authors.initials: FJ
authors.lastname: Daha
authors.affiliation: Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Iran.|Biomolecular imaging analysis group (BIAG), Research Center for Molecular and Cellular Imaging (RCMCI), Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Oghabian
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000378:metabolism; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D013667:Technetium / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D003287:Contrast Media; D005290:Ferric Compounds; C434325:MUC-1 monoclonal antibody; D058185:Magnetite Nanoparticles; D018396:Mucin-1; C000499:ferric oxide; D013667:Technetium
keywords: C595 antibody; USPIO; biodistribution; breast cancer; nanoparticles; protein corona