title: Detection of Lymph Node Metastases with SERRS Nanoparticles.
abstract: The accurate detection of lymph node metastases in prostate cancer patients is important to direct treatment decisions. Our goal was to develop an intraoperative imaging approach to distinguish normal from metastasized lymph nodes. We aimed at developing and testing gold-silica surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles that demonstrate high uptake within normal lymphatic tissue and negligible uptake in areas of metastatic replacement.
  
  
  
  We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancer mouse model using PC-3 cells transduced with mCherry fluorescent protein. Tumor-bearing mice (n = 6) and non-tumor-bearing control animals (n = 4) were injected intravenously with 30 fmol/g SERRS nanoparticles. After 16-18 h, the retroperitoneal lymph nodes were scanned in situ and ex vivo with a Raman imaging system and a handheld Raman scanner and data corroborated with fluorescence imaging for mCherry protein expression and histology.
  
  
  
  The SERRS nanoparticles demonstrated avid homing to normal lymph nodes, but not to metastasized lymph nodes. In cases where lymph nodes were partially infiltrated by tumor cells, the SERRS signal correctly identified, with sub-millimeter precision, healthy from metastasized components.
  
  
  
  This study serves as a first proof-of-principle that SERRS nanoparticles enable high precision and rapid intraoperative discrimination between normal and metastasized lymph nodes.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.|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: 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.
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 of the City University of New York, New York, NY, 10065, USA.|Department of Chemistry, The Graduate Center of the 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: Chrysafis
authors.initials: C
authors.lastname: Andreou
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: James A
authors.initials: JA
authors.lastname: Eastham
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: Karim A
authors.initials: KA
authors.lastname: Touijer
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: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. kircherm@mskcc.org.|Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. kircherm@mskcc.org.|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; D004195:Disease Models, Animal; D005453:Fluorescence; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000473:pathology; D012815:Signal Processing, Computer-Assisted; D013059:Spectrum Analysis, Raman / Q000379:methods*
keywords: Intraoperative imaging; Lymph node metastasis; Prostate cancer; Raman imaging; Surface-enhanced resonance Raman scattering