Spaliviero Massimiliano, Harmsen Stefan, Huang Ruimin, Wall Matthew A, Andreou Chrysafis, Eastham James A, Touijer Karim A, Scardino Peter T, Kircher Moritz F
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.
Mol Imaging Biol. 2016 Oct;18(5):677-85. doi: 10.1007/s11307-016-0932-2.
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.
准确检测前列腺癌患者的淋巴结转移对于指导治疗决策至关重要。我们的目标是开发一种术中成像方法，以区分正常淋巴结和转移淋巴结。我们旨在开发和测试金-二氧化硅表面增强共振拉曼光谱（SERRS）纳米颗粒，该纳米颗粒在正常淋巴组织中摄取率高，而在转移替代区域摄取率可忽略不计。
我们使用转导了mCherry荧光蛋白的PC-3细胞，在原位前列腺癌小鼠模型中评估SERRS纳米颗粒描绘淋巴结转移的能力。给荷瘤小鼠（n = 6）和无瘤对照动物（n = 4）静脉注射30 fmol/g的SERRS纳米颗粒。16 - 18小时后，使用拉曼成像系统和手持式拉曼扫描仪对腹膜后淋巴结进行原位和离体扫描，并将数据与mCherry蛋白表达的荧光成像和组织学结果进行对照。
SERRS纳米颗粒显示出对正常淋巴结的强烈归巢，但对转移淋巴结则不然。在淋巴结部分被肿瘤细胞浸润的情况下，SERRS信号以亚毫米精度正确识别出健康成分和转移成分。
本研究首次证明了SERRS纳米颗粒能够在术中高精度、快速地区分正常淋巴结和转移淋巴结。
