Dual-Modality Noninvasive Mapping of Sentinel Lymph Node by Photoacoustic and Near-Infrared Fluorescent Imaging Using Dye-Loaded Mesoporous Silica Nanoparticles.

The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we developed an imaging contrast system based on fluorescent dye-loaded mesoporous silica nanoparticles (MSNPs) that integrate near-infrared (NIR) fluorescent and photoacoustic (PA) imaging modalities for efficient SLN mapping. By balancing the ratio of dye and nanoparticles for simultaneous optimization of dual-modality imaging (NIR and PA), the dye encapsulated MSNP platform was set up to generate both a moderate NIR emission and PA signals simultaneously. Moreover, the underlying mechanisms of the relevance between optical and PA properties were discovered. Subsequently, dual-modality imaging was achieved to visualize tumor draining SLNs up to 2 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate and contrast between metastatic and normal SLNs were observed both in vivo and ex vivo. Based on all these imaging data, it was demonstrated that the dye-loaded MSNPs allow detection of regional lymph nodes in vivo with time-domain NIR fluorescent and PA imaging methods efficiently.

[1]  Yun Sun,et al.  Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node. , 2011, Biomaterials.

[2]  Benoit Dubertret,et al.  Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity. , 2010, ACS nano.

[3]  S. Stacker,et al.  Focus on lymphangiogenesis in tumor metastasis. , 2005, Cancer cell.

[4]  Xiaoyuan Chen Multimodality imaging of tumor integrin alphavbeta3 expression. , 2006, Mini reviews in medicinal chemistry.

[5]  X. Wang,et al.  Bright and stable Cy3-encapsulated fluorescent silica nanoparticles with a large Stokes shift , 2012 .

[6]  Weihong Tan,et al.  Multicolor FRET silica nanoparticles by single wavelength excitation. , 2006, Nano letters.

[7]  Lihong V. Wang,et al.  Noninvasive photoacoustic identification of sentinel lymph nodes containing methylene blue in vivo in a rat model. , 2008, Journal of biomedical optics.

[8]  E. van Marck,et al.  Increased Sentinel Lymph Node Lymphangiogenesis is Associated with Nonsentinel Axillary Lymph Node Involvement in Breast Cancer Patients with a Positive Sentinel Node , 2007, Clinical Cancer Research.

[9]  Imaging tumor-induced sentinel lymph node lymphangiogenesis with LyP-1 peptide , 2011, Amino Acids.

[10]  James A J Fitzpatrick,et al.  Sentinel lymph node imaging using quantum dots in mouse tumor models. , 2007, Bioconjugate chemistry.

[11]  François Guillemin,et al.  Fluorescence Imaging and Whole-Body Biodistribution of Near-Infrared-Emitting Quantum Dots after Subcutaneous Injection for Regional Lymph Node Mapping in Mice , 2010, Molecular Imaging and Biology.

[12]  T. Desmettre,et al.  Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. , 2000, Survey of ophthalmology.

[13]  Tristan Barrett,et al.  Simultaneous multicolor imaging of five different lymphatic basins using quantum dots. , 2007, Nano letters.

[14]  Dong Chen,et al.  The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo. , 2011, ACS nano.

[15]  N. Hansen,et al.  The benefits and limitations of sentinel lymph node biopsy , 2006, Current treatment options in oncology.

[16]  Kai Yang,et al.  Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. , 2011, Angewandte Chemie.

[17]  Fan Zhang,et al.  Preclinical Lymphatic Imaging , 2011, Molecular Imaging and Biology.

[18]  A. V. D. Van Der Zee,et al.  The role of sentinel node biopsy in gynecological cancer: a review , 2009, Current opinion in oncology.

[19]  Wei Feng,et al.  Cubic sub-20 nm NaLuF(4)-based upconversion nanophosphors for high-contrast bioimaging in different animal species. , 2012, Biomaterials.

[20]  J. Sleeman,et al.  Do all roads lead to Rome? Routes to metastasis development , 2011, International journal of cancer.

[21]  Lixin Lang,et al.  Long-term multimodal imaging of tumor draining sentinel lymph nodes using mesoporous silica-based nanoprobes. , 2012, Biomaterials.

[22]  Kari Alitalo Lymphangiogenesis in development and human disease , 2007 .

[23]  Bernd J Pichler,et al.  Latest Advances in Molecular Imaging Instrumentation , 2008, Journal of Nuclear Medicine.

[24]  Manojit Pramanik,et al.  In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node , 2009, Physics in medicine and biology.

[25]  Ruikang K. Wang,et al.  Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes. , 2011, Nano letters.

[26]  K. Alitalo,et al.  The lymphatic vasculature in disease , 2011, Nature Medicine.

[27]  Xin Cai,et al.  Noninvasive photoacoustic and fluorescence sentinel lymph node identification using dye-loaded perfluorocarbon nanoparticles. , 2011, ACS nano.

[28]  Andrew A. Burns,et al.  Fluorescent core-shell silica nanoparticles: towards "Lab on a Particle" architectures for nanobiotechnology. , 2006, Chemical Society reviews.

[29]  M. Bruchez,et al.  Long-term persistence and spectral blue shifting of quantum dots in vivo. , 2009, Nano letters.

[30]  V. Sondak,et al.  Sentinel lymph node biopsy for melanoma: indications and rationale. , 2009, Cancer control : journal of the Moffitt Cancer Center.

[31]  Li Tang,et al.  Aptamer-functionalized, ultra-small, monodisperse silica nanoconjugates for targeted dual-modal imaging of lymph nodes with metastatic tumors. , 2012, Angewandte Chemie.

[32]  Dong Chen,et al.  The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. , 2010, Biomaterials.

[33]  E. Mittra,et al.  Novel Strategy for a Cocktail 18F-Fluoride and 18F-FDG PET/CT Scan for Evaluation of Malignancy: Results of the Pilot-Phase Study , 2009, Journal of Nuclear Medicine.

[34]  G. Janetschek,et al.  Technology Insight: radioguided sentinel lymph node dissection in the staging of prostate cancer , 2006, Nature Clinical Practice Urology.

[35]  C. Tsopelas Particle size analysis of (99m)Tc-labeled and unlabeled antimony trisulfide and rhenium sulfide colloids intended for lymphoscintigraphic application. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  Younan Xia,et al.  Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model. , 2009, Nano letters.

[37]  Mark C Kelley,et al.  Lymphatic mapping and sentinel lymphadenectomy for breast cancer. , 2004, American journal of surgery.

[38]  G. S. Mijnhout,et al.  Radiopharmaceuticals in sentinel lymph-node detection – an overview , 1999, European Journal of Nuclear Medicine.

[39]  M. Detmar,et al.  Lymphangiogenesis and cancer metastasis , 2009, Journal of cellular and molecular medicine.

[40]  M. Oghabian,et al.  Detection sensitivity of lymph nodes of various sizes using USPIO nanoparticles in magnetic resonance imaging. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[41]  B. MacCraith,et al.  Experimental and theoretical studies of the optimisation of fluorescence from near-infrared dye-doped silica nanoparticles , 2009, Analytical and bioanalytical chemistry.

[42]  K. Alitalo,et al.  Lymphangiogenesis: Molecular Mechanisms and Future Promise , 2010, Cell.

[43]  Quing Zhu,et al.  Synthesis and fluorescent characteristics of imidazole–indocyanine green conjugates , 2011 .