title: A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.
abstract: The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy.
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305-4034, USA. Electronic address: pkempen@stanford.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kempen
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA 94305-5427, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Radiology, Weill Cornell Medical College, New York, NY 10021, USA; Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Center for Molecular Imaging and Nanotechnology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA 94305-5427, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: de la Zerda
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA 94305-5427, USA.
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Zavaleta
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA 94305-5427, USA.
authors.forename: Jesse V
authors.initials: JV
authors.lastname: Jokerst
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305-4034, USA; Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA 94305-5427, USA; Department of Bio-engineering and Bio-X Program, Stanford University, Stanford, CA 94305-5427, USA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305-4034, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sinclair
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D008853:Microscopy / Q000379:methods*; D053758:Nanoparticles / Q000032:analysis; D061848:Optical Imaging / Q000379:methods*
keywords: Cancer diagnosis; Correlative microscopy; Nanotechnology; Optical microscopy; Scanning electron microscopy