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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      RGD targeted poly( L-glutamic acid)-cystamine-(Gd-DO3A) conjugate for detecting angiogenesis biomarker α νβ 3 integrin with MR T 1 mapping

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          Abstract

          Cyclic Arg-Gly-Asp-D-Phe-Lys [c(RGDfK)] targeted poly( L-glutamic acid) (PGA)-(Gd-DO3A) conjugate with a biodegradable cystamine spacer was prepared and evaluated for in vivo detection of an angiogenesis biomarker, α νβ 3 integrin, in neoplastic tissues with T 1 mapping, a quantitative magnetic resonance imaging (MRI) technique. The binding activity of the c(RGDfK) containing conjugate was investigated using in vitro vitronectin assay with human prostate carcinoma DU145 cell line and Kaposi’s sarcoma SLK cell line. The peptide c(RGDfK) and PGA-cystamine-(Gd-DO3A) conjugate were used as controls. The binding affinity of polymer bound c(RGDfK) was slightly lower than free c(RGDfK) peptide. The RGD targeted conjugate had higher binding affinity to the DU145 cells than the SLK cells, which was consistent to free c(RGDfK). The imaging of α νβ 3 integrin with targeted PGA-cystamine-(Gd-DO3A) was evaluated in nude mice bearing DU145 and SLK xenografts at a dose of 5 μmol-Gd/kg. The targeted conjugate demonstrated higher in vivo binding affinity to the DU145 xenografts than the SLK xenografts, resulting in a significant decrease of T 1 values of water protons in the periphery of the DU145 tumors as shown in the MR T 1 maps. No significant decrease of T 1 values was observed in the SLK tumor with the targeted conjugate and in both tumors with the non-targeted conjugate. The targeted polymeric Gd(III) chelate conjugate with a degradable spacer has the potential to be a new paradigm for safe and effective probes in molecular imaging with quantitative MR T 1 mapping.

          Most cited references24

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          Requirement of vascular integrin alpha v beta 3 for angiogenesis.

          Angiogenesis depends on the adhesive interactions of vascular cells. The adhesion receptor integrin alpha v beta 3 was identified as a marker of angiogenic vascular tissue. Integrin alpha v beta 3 was expressed on blood vessels in human wound granulation tissue but not in normal skin, and it showed a fourfold increase in expression during angiogenesis on the chick chorioallantoic membrane. In the latter assay, a monoclonal antibody to alpha v beta 3 blocked angiogenesis induced by basic fibroblast growth factor, tumor necrosis factor-alpha, and human melanoma fragments but had no effect on preexisting vessels. These findings suggest that alpha v beta 3 may be a useful therapeutic target for diseases characterized by neovascularization.
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            Pathology: cancer cells compress intratumour vessels.

            The delivery of therapeutic drugs to solid tumours may be impaired by structural and functional abnormalities in blood and lymphatic vessels. Here we provide evidence that proliferating cancer cells cause intratumour vessels to compress and collapse. By reducing this compressive mechanical force and opening vessels, cytotoxic cancer treatments have the potential to increase blood perfusion, thereby improving drug delivery.
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              Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state.

              A novel, fully 3D, high-resolution T(1) and T(2) relaxation time mapping method is presented. The method is based on steady-state imaging with T(1) and T(2) information derived from either spoiling or fully refocusing the transverse magnetization following each excitation pulse. T(1) is extracted from a pair of spoiled gradient recalled echo (SPGR) images acquired at optimized flip angles. This T(1) information is combined with two refocused steady-state free precession (SSFP) images to determine T(2). T(1) and T(2) accuracy was evaluated against inversion recovery (IR) and spin-echo (SE) results, respectively. Error within the T(1) and T(2) maps, determined from both phantom and in vivo measurements, is approximately 7% for T(1) between 300 and 2000 ms and 7% for T(2) between 30 and 150 ms. The efficiency of the method, defined as the signal-to-noise ratio (SNR) of the final map per voxel volume per square root scan time, was evaluated against alternative mapping methods. With an efficiency of three times that of multipoint IR and three times that of multiecho SE, our combined approach represents the most efficient of those examined. Acquisition time for a whole brain T(1) map (25 x 25 x 10 cm) is less than 8 min with 1 mm(3) isotropic voxels. An additional 7 min is required for an identically sized T(2) map and postprocessing time is less than 1 min on a 1 GHz PIII PC. The method therefore permits real-time clinical acquisition and display of whole brain T(1) and T(2) maps for the first time. Copyright 2003 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                June 2007
                June 2007
                : 2
                : 2
                : 191-199
                Affiliations
                [1 ]Departments of Pharmaceutics and Pharmaceutical Chemistry;
                [2 ]Radiology and Materials Science and
                [3 ]Engineering, University of Utah, Salt Lake City, UT, USA
                Author notes
                Correspondence: Zheng-Rong Lu, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, USA, Tel +1 801 587 9450, Fax +1 801 585 3614, Email zhengrong.lu@ 123456utah.edu
                Article
                ijn-2-191
                2673968
                17722547
                268fa006-2bb3-42f8-84d9-3119eac55e14
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Original Research

                Molecular medicine
                mr t1 mapping,rgd,ανβ3 integrin,mri contrast agent,pga-cystamine-(gd-do3a)
                Molecular medicine
                mr t1 mapping, rgd, ανβ3 integrin, mri contrast agent, pga-cystamine-(gd-do3a)

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