title: Surface-enhanced resonance Raman scattering nanostars for high-precision cancer imaging.
abstract: The inability to visualize the true extent of cancers represents a significant challenge in many areas of oncology. The margins of most cancer types are not well demarcated because the cancer diffusely infiltrates the surrounding tissues. Furthermore, cancers may be multifocal and characterized by the presence of microscopic satellite lesions. Such microscopic foci represent a major reason for persistence of cancer, local recurrences, and metastatic spread, and are usually impossible to visualize with currently available imaging technologies. An imaging method to reveal the true extent of tumors is desired clinically and surgically. We show the precise visualization of tumor margins, microscopic tumor invasion, and multifocal locoregional tumor spread using a new generation of surface-enhanced resonance Raman scattering (SERRS) nanoparticles, which are termed SERRS nanostars. The SERRS nanostars feature a star-shaped gold core, a Raman reporter resonant in the near-infrared spectrum, and a primer-free silication method. In genetically engineered mouse models of pancreatic cancer, breast cancer, prostate cancer, and sarcoma, and in one human sarcoma xenograft model, SERRS nanostars enabled accurate detection of macroscopic malignant lesions, as well as microscopic disease, without the need for a targeting moiety. Moreover, the sensitivity (1.5 fM limit of detection) of SERRS nanostars allowed imaging of premalignant lesions of pancreatic and prostatic neoplasias. High sensitivity and broad applicability, in conjunction with their inert gold-silica composition, render SERRS nanostars a promising imaging agent for more precise cancer imaging and resection.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Harmsen
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Department of Chemistry, Hunter College, City University of New York, New York, NY 10065, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wall
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Hazem
authors.initials: H
authors.lastname: Karabeber
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Samii
authors.affiliation: Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Spaliviero
authors.affiliation: Tri-Institutional Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medical College, New York, NY 10065, USA. Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: White
authors.affiliation: Tri-Institutional Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medical College, New York, NY 10065, USA. Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Monette
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: O'Connor
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Pitter
authors.affiliation: Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Sastra
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Saborowski
authors.affiliation: Human Biology Division and Solid Tumor Translational Research, Fred Hutchinson Cancer Research Center, Alvord Brain Tumor Center, University of Washington, Seattle, WA 98109, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
authors.affiliation: Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Olive
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Howard Hughes Medical Institute, New York, NY 10065, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lowe
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Blasberg
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA. kircherm@mskcc.org.
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053758:Nanoparticles; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis*; D010873:Pinocytosis; D011230:Precancerous Conditions / Q000473:pathology; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014018:Tissue Distribution