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New Nanosized Biocompatible MR Contrast Agents Based on Lysine-Dendri-Graft Macromolecules

  1. Author:
    Ogawa, M.
    Regino, C. A. S.
    Marcelino, B.
    Williams, M.
    Kosaka, N.
    Bryant, L. H.
    Choyke, P. L.
    Kobayashi, H.

  2. Author Address

    [Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. NIH, Lab Diagnost Radiol Res Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.;Kobayashi, H, NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC 1088, Bethesda, MD 20892 USA.;kobayash@mail.nih.gov
    1. Year: 2010
    2. Date: May
  2. Journal: Bioconjugate Chemistry
    1. 21
    2. 5
    3. Pages: 955-960
  4. Type of Article: Article
  5. ISSN: 1043-1802
  1. Abstract:

    Paramagnetic nanomaterials for use as magnetic resonance imaging (MRI) contrast agents have higher relaxivity than conventional low molecular weight MRI agents. However, the biocompatibility and pharmacokinetics of such nanomaterials will strongly affect the likelihood of clinical approval. We synthesized MRI contrast agents based on biocompatible lysine-dendri-grafts: Gd-BzDTPA-lysineG2 and Gd-BzDTPA-lysineG3. The relaxivity of Gd-BzDTPA-lysineG2 and Gd-BzDTPA-lysineG3 increased with sample temperature, while the relaxivity of Gd-BzDTPA-PAMAMG4 decreased with increasing sample temperature. The increase in relaxivity with increasing temperature may be attributed to accessibility of water to the internal Gd chelates with lysine-dendri-grafts, which does not occur with PAMAM dendrimers. Gd-BzDTPA-lysineG3 had a long intravascular half-life but were largely excreted by the kidneys. Therefore, Gd-BzDTPA-lysineG3 enhanced the blood vessels for longer periods than Gd-BzDTPA-PAMAMG4, but was still excreted through the kidney. Because of their biocompatibility, desirable magneto-physical characteristics and favorable pharmacokinetics, which are derived from different interior structures rather than the physical size, lysine-dendri-graft MRI contrast agents may be feasible for clinical use.

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External Sources

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  2. DOI: 10.1021/bc9005442
  3. View record in Web of Science®
  4. WOS: 000277683300021

Library Notes

  1. Fiscal Year: FY2009-2010
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