title: In vivo lymphatic imaging of a human inflammatory breast cancer model.
abstract: BACKGROUND
  Inflammatory breast cancer (IBC) remains the most aggressive type of breast cancer with the greatest potential for metastasis and as a result, the highest mortality rate. IBC cells invade and metastasize through dermal lymphatic vessels; however, it is unknown how lymphatic drainage patterns change during IBC growth and metastasis. Herein, we non-invasively and longitudinally imaged lymphatics in an animal model of IBC using near-infrared fluorescence (NIRF) imaging.
  
  
  METHODS
  Mice were imaged in vivo prior to, and up to 11 weeks after subcutaneous or orthotopic inoculation of human IBC SUM149 cells, which were stably transfected with infrared fluorescence protein (iRFP) gene reporter (SUM149-iRFP), following intradermal (i.d.) injection of indocyanine green (ICG).
  
  
  RESULTS
  Fluorescence images showed well-defined lymphatic vessels prior to SUM149-iRFP inoculation. However, altered lymphatic drainage patterns including rerouting of lymphatic drainage were detected in mice with SUM149-iRFP, due to lymphatic obstruction of normal lymphatic drainages caused by tumor growth. In addition, we observed tortuous lymphatic vessels and extravasation of ICG-laden lymph in mice with SUM149-iRFP. We also observed increased and dilated fluorescent lymphatic vessels in the tumor periphery, which was confirmed by ex vivo immunohistochemical staining of lymphatic vessels.
  
  
  CONCLUSIONS
  Our pre-clinical studies demonstrate that non-invasive NIRF imaging can provide a method to assess changes in lymphatic drainage patterns during IBC growth and metastasis.
authors.affiliation: 1. Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030; ; 2. The University of Texas Graduate School of Biomedical Sciences at Houston. The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
authors.forename: Germaine D
authors.initials: GD
authors.lastname: Agollah
authors.affiliation: 1. Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030;
authors.forename: Grace
authors.initials: G
authors.lastname: Wu
authors.affiliation: 1. Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030;
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
authors.affiliation: 1. Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030;
authors.forename: Sunkuk
authors.initials: S
authors.lastname: Kwon
keywords: inflammatory breast cancer; lymphangiogenesis.; lymphatic system; near-infrared fluorescence imaging