Visualisation of sentinel lymph node with indium-based near infrared emitting Quantum Dots in a murine metastatic breast cancer model

PLoS One. 2012;7(8):e44433. doi: 10.1371/journal.pone.0044433. Epub 2012 Aug 30.

Abstract

Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near-infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS(2)/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma - mass spectroscopy (ICP-MS) as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cell Line, Tumor
  • Disease Models, Animal
  • Erythrocytes / cytology
  • Female
  • Fibroblasts / cytology
  • Fluorescence
  • Hemolysis
  • Humans
  • Indium*
  • Lymph Nodes / pathology*
  • Mammary Neoplasms, Animal / diagnosis*
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis
  • Quantum Dots*
  • Spectroscopy, Near-Infrared*
  • Time Factors
  • Tissue Distribution
  • Toxicity Tests

Substances

  • Indium

Grants and funding

This work was supported by the Institut National du Cancer (INCa), the Ligue Nationale contre le cancer, the Lorraine Region and the Centre Alexis Vautrin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.