Localisation des ganglions sentinelles au moyen de quantum dots : application au cancer du sein

Abstract : Lymph node (LN) status is the most important prognostic factor in breast cancer patients and a determinant predictor of recurrence and survival. In the treatment of operable breast cancers with a size inferior of 3 cm, the sentinel lymph node biopsy (SLNB) substitutes the axillary LN dissection. However, this technique requires the simultaneous use of a radiocolloid and a physiologic dye, which present several secondary effects. Thus, our strategy was to test in preclinical model the new fluorescent markers, Quantum Dots (QDs) for SLNB. A study on in vivo axillary LN (ALN) mapping by light induced fluorescence was performed after subcutaneous (s.c.) injection of red-emitting QDs and their ex vivo quantification was realized by spectrofluorimetry for up to 24 h. We showed a fast and selective accumulation of QDs in ALN in healthy mice. An in vivo study on localization of 2 regional LNs by fluorescence imaging was carried out after the s.c. administration of near-infrared (NIR) emitting QDs along with ex vivo biodistribution study by mass spectroscopy (ICP-MS). Obtained results shown that fluorescence imaging can be used after QDs injection to map and follow their accumulation in superficial LNs in healthy mice. To approach the human clinic in a best possible way, sentinel ALN mapping was investigated after s.c. delivery of NIR emitting QDs in murine breast cancer model by fluorescence imaging. Two techniques for LN metastasis detection were used and compared: conventional histology and RT-PCR. All sentinel ALNs were located in vivo by imaging except one ALNs which was completely invaded by cancer cells and best incidence of LN metastasis was registered by RT-PCR (60 %). Thus, QDs could be used as a substitute for the markers currently employed in SLNB in breast cancers.
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Emilie Pic. Localisation des ganglions sentinelles au moyen de quantum dots : application au cancer du sein. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2009. Français. ⟨NNT : 2009NAN10087⟩. ⟨tel-01748312⟩

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