title: Time-course imaging of therapeutic functional tumor vascular normalization by antiangiogenic agents.
abstract: We describe here new technology that enables noninvasive imaging of therapeutic functional normalization of tumor blood vessels by antiangiogenic agents. Noninvasive variable-magnification in vivo-fluorescence imaging as well as fluorescence tomography was used to visualize functional vessel normalization. Changes in the same vessel before and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was shown by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense(750), was retained only in tumors after either anti-VEGF antibody or rapamycin treatment, as visualized by noninvasive fluorescence tomography. The antiangiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of paclitaxel because of increased drug penetration throughout the tumor. The optical imaging technology described here is thus a powerful, noninvasive, time-course imaging tool of functional tumor vessel normalization and its therapeutic consequences.
authors.affiliation: Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, AMB N339, MC1089, Chicago, IL 60637, USA.
authors.forename: Qingbei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Vytas
authors.initials: V
authors.lastname: Bindokas
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Hanli
authors.initials: H
authors.lastname: Fan
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: H Rosie
authors.initials: HR
authors.lastname: Xing
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D020286:Pericytes / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents