title: Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells.
abstract: We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner.
authors.affiliation: Quantitative Diagnostic Imaging Program, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan. harukay@ngt.ndu.ac.jp.
authors.forename: Haruka
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Quantitative Diagnostic Imaging Program, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan. tsuchimochi@ngt.ndu.ac.jp.|Department of Oral and Maxillofacial Radiology, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan. tsuchimochi@ngt.ndu.ac.jp.|Advanced Research Center, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan. tsuchimochi@ngt.ndu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuchimochi
authors.affiliation: Department of Oral and Maxillofacial Radiology, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan. hayama@ngt.ndu.ac.jp.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayama
authors.affiliation: Advanced Research Center, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan. kawase@dent.niigata-u.ac.jp.|Division of Oral Bioengineering, Institute of Medicine and Dentistry, Niigata University, Niigata 951-8514, Japan. kawase@dent.niigata-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Advanced Research Center, The Nippon Dental University School of Life Dentistry at Niigata, Niigata 951-8580, Japan. ntsuboka@eng.niigata-u.ac.jp.|Faculty of Engineering, Niigata University, Niigata 950-2181, Japan. ntsuboka@eng.niigata-u.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Tsubokawa
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D007150:Immunohistochemistry; D007208:Indocyanine Green / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared; D013667:Technetium / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D006834:Hydrazines; D007208:Indocyanine Green; D011073:Polyamines; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D012822:Silicon Dioxide; D013667:Technetium; C417561:Alexa 488 hydrazide; C531249:Poly(amidoamine); C508053:ERBB2 protein, human
keywords: 99mTc; HER2; ICG; MDA-MB231; NIR; SK-BR3; athymic mice; dual-imaging probe; silica nanoparticles; xenograft