title: Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle.
abstract: Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site-specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4-fold increase in its perfusion as well as a 2- to 4-fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By transdermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels.
authors.affiliation: *Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany; and Department of Medical Physics in Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Schröder
authors.affiliation: *Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany; and Department of Medical Physics in Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany.
authors.forename: Dorde
authors.initials: D
authors.lastname: Komljenovic
authors.affiliation: *Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany; and Department of Medical Physics in Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.affiliation: *Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany; and Department of Medical Physics in Radiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany korff@physiologie.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Korff
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000069286:Bortezomib / Q000009:adverse effects / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004428:Ear Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology
chemical_list: D000069286:Bortezomib
keywords: angiogenesis; blood vessel growth; bortezomib; mouse model; perfusion