Massimiliano Spaliviero1,2, Stefan Harmsen1, Ruimin Huang1, Matthew A Wall1,3,4, Chrysafis Andreou1, James A Eastham2, Karim A Touijer2, Peter T Scardino2, Moritz F Kircher5,6,7. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. 2. Urology Service, Department of Surgery, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. 3. Department of Chemistry, Hunter College of the City University of New York, New York, NY, 10065, USA. 4. Department of Chemistry, The Graduate Center of the City University of New York, New York, NY, 10065, USA. 5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. kircherm@mskcc.org. 6. Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. kircherm@mskcc.org. 7. Department of Radiology, Weill Cornell Medical College, New York, NY, 10065, USA. kircherm@mskcc.org.
Abstract
PURPOSE: 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. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: The accurate detection of lymph node metastases in prostate cancerpatients 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. PROCEDURES: We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancermouse 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. RESULTS: 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. CONCLUSIONS: 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: Kenneth G Nepple; Henry M Rosevear; Alan H Stolpen; James A Brown; Richard D Williams Journal: Urol Oncol Date: 2011-06-12 Impact factor: 3.498
Authors: Henk G van der Poel; Tessa Buckle; Oscar R Brouwer; Renato A Valdés Olmos; Fijs W B van Leeuwen Journal: Eur Urol Date: 2011-04-01 Impact factor: 20.096
Authors: Patrick Wunderbaldinger; Lee Josephson; Christoph Bremer; Anna Moore; Ralph Weissleder Journal: Magn Reson Med Date: 2002-02 Impact factor: 4.668
Authors: Firas Abdollah; Maxine Sun; Rodolphe Thuret; Lars Budäus; Claudio Jeldres; Markus Graefen; Alberto Briganti; Paul Perrotte; Patrizio Rigatti; Francesco Montorsi; Pierre I Karakiewicz Journal: Eur Urol Date: 2010-09-28 Impact factor: 20.096
Authors: Ofer Yossepowitch; Scott E Eggener; Angel M Serio; Brett S Carver; Fernando J Bianco; Peter T Scardino; James A Eastham Journal: Eur Urol Date: 2007-10-12 Impact factor: 20.096
Authors: L Cheng; E J Bergstralh; J C Cheville; J Slezak; F A Corica; H Zincke; M L Blute; D G Bostwick Journal: Am J Surg Pathol Date: 1998-12 Impact factor: 6.394
Authors: Stefan Harmsen; Ruimin Huang; Matthew A Wall; Hazem Karabeber; Jason M Samii; Massimiliano Spaliviero; Julie R White; Sébastien Monette; Rachael O'Connor; Kenneth L Pitter; Stephen A Sastra; Michael Saborowski; Eric C Holland; Samuel Singer; Kenneth P Olive; Scott W Lowe; Ronald G Blasberg; Moritz F Kircher Journal: Sci Transl Med Date: 2015-01-21 Impact factor: 17.956
Authors: Moritz F Kircher; Adam de la Zerda; Jesse V Jokerst; Cristina L Zavaleta; Paul J Kempen; Erik Mittra; Ken Pitter; Ruimin Huang; Carl Campos; Frezghi Habte; Robert Sinclair; Cameron W Brennan; Ingo K Mellinghoff; Eric C Holland; Sanjiv S Gambhir Journal: Nat Med Date: 2012-04-15 Impact factor: 53.440
Authors: Stefan Harmsen; Matthew A Bedics; Matthew A Wall; Ruimin Huang; Michael R Detty; Moritz F Kircher Journal: Nat Commun Date: 2015-03-24 Impact factor: 14.919
Authors: Chrysafis Andreou; Volker Neuschmelting; Darjus-Felix Tschaharganeh; Chun-Hao Huang; Anton Oseledchyk; Pasquale Iacono; Hazem Karabeber; Rivka R Colen; Lorenzo Mannelli; Scott W Lowe; Moritz F Kircher Journal: ACS Nano Date: 2016-05-10 Impact factor: 15.881
Authors: Suchetan Pal; Stefan Harmsen; Anton Oseledchyk; Hsiao-Ting Hsu; Moritz F Kircher Journal: Adv Funct Mater Date: 2017-07-06 Impact factor: 18.808
Authors: Ruimin Huang; Stefan Harmsen; Jason M Samii; Hazem Karabeber; Kenneth L Pitter; Eric C Holland; Moritz F Kircher Journal: Theranostics Date: 2016-05-07 Impact factor: 11.556
Authors: Matthew A Wall; Travis M Shaffer; Stefan Harmsen; Darjus-Felix Tschaharganeh; Chun-Hao Huang; Scott W Lowe; Charles Michael Drain; Moritz F Kircher Journal: Theranostics Date: 2017-07-22 Impact factor: 11.556