title: Visualisation of sentinel lymph node with indium-based near infrared emitting Quantum Dots in a murine metastatic breast cancer model.
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.
authors.affiliation: Université de Lorraine, Centre de Recherche en Automatique de Nancy (CRAN), UMR 7039, Vandoeuvre-lès-Nancy, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Helle
authors.forename: Elsa
authors.initials: E
authors.lastname: Cassette
authors.forename: Lina
authors.initials: L
authors.lastname: Bezdetnaya
authors.forename: Thomas
authors.initials: T
authors.lastname: Pons
authors.forename: Agnès
authors.initials: A
authors.lastname: Leroux
authors.forename: François
authors.initials: F
authors.lastname: Plénat
authors.forename: François
authors.initials: F
authors.lastname: Guillemin
authors.forename: Benoît
authors.initials: B
authors.lastname: Dubertret
authors.forename: Frédéric
authors.initials: F
authors.lastname: Marchal
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005453:Fluorescence; D006461:Hemolysis; D006801:Humans; D007204:Indium; D008198:Lymph Nodes / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D045663:Quantum Dots; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors; D014018:Tissue Distribution; D018675:Toxicity Tests
chemical_list: D007204:Indium