In vivo microcartography and subcellular imaging of tumor angiogenesis: A novel platform for translational angiogenesis research Journal Article

   

Authors:	Dunphy, M. P. S.; Entenberg, D.; Toledo-Crow, R.; Larson, S. M.
Article Title:	In vivo microcartography and subcellular imaging of tumor angiogenesis: A novel platform for translational angiogenesis research
Abstract:	Purpose: To eliminate the variable of tumor heterogeneity from a novel in vivo model of tumor angiogenesis. Experimental design: We developed a method to navigate tumor neovasculature in a living tissue microenvironment, enabling relocation of a cell- or microregion-of-interest, for serial in vivo imaging. Orthotopic melanoma was grown, in immunocompetent Tie2GFP mice. Intravital multiphoton fluorescence and confocal reflectance imaging was performed, on a custom microscope with motorized stage and coordinate navigation software. A point within a Tie2GFP+ microvessel was selected for relocation. Custom software predicted target coordinates based upon reference points (tissue-embedded polystyrene beads) and baseline target coordinates. Mice were removed from the stage to make previously-obtained target coordinates invalid in subsequent imaging. Results: Coordinate predictions always relocated target points, in vivo, to within 10-200 μm (within a single 40× field-of-view). The model system provided a virtual living histology of tumor neovascularization and microenvironment, with subcellular spatial resolution and hemodynamic information. Conclusions: The navigation procedure, termed in vivo microcartography, permits control of tissue heterogeneity, as a variable. Tie2 may be the best reporter gene identified, to-date, for intravital microscopy of tumor angiogenesis. This novel model system should strengthen intravital microscopy in its historical role as a vital tool in oncology, angiogenesis research, and angiotherapeutic drug development. © 2009 Elsevier Inc. All rights reserved.
Keywords:	controlled study; microscopy; nonhuman; neoplasms; reproducibility of results; mouse; animals; mice; mus; melanoma; confocal microscopy; image analysis; microscopy, confocal; green fluorescent protein; animal experiment; animal model; in vivo study; molecular imaging; diagnostic imaging; angiogenesis; neovascularization, pathologic; animalia; luminescent proteins; mice, transgenic; imaging system; gene identification; melanoma, experimental; reporter gene; cellular distribution; green fluorescent proteins; microenvironment; receptor; polystyrene; computer program; angiogenesis inhibitors; intravital microscopy; neovascularization; reflectance; tie2; transgenic; vascular disrupting agents; vasculopathy; angiopoietin receptor; computer prediction; hemodynamic monitoring; in vivo microcartography; microvasculature; multiphoton microscopy; tumor vascularization; microscopy, fluorescence, multiphoton; microvessels; receptor, tie-2
Journal Title:	Microvascular Research
Volume:	78
Issue:	1
ISSN:	0026-2862
Publisher:	Elsevier Inc.
Date Published:	2009-06-01
Start Page:	51
End Page:	56
Language:	English
DOI:	10.1016/j.mvr.2009.03.008
PUBMED:	19362098
PROVIDER:	scopus
PMCID:	PMC2739383
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-67349179952&partnerID=40&md5=952eb1ea85d50b5317bee404b9d9aa1a
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 30 November 2010" - "CODEN: MIVRA" - "Source: Scopus"

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