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Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

  1. Author:
    Nwe, K.
    Bernardo, M.
    Regino, C. A. S.
    Williams, M.
    Brechbiel, M. W.

  2. Author Address

    [Brechbiel, M. W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Regino, C. A. S.; Williams, M.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Bernardo, M.] NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.;Brechbiel, MW, NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.;martinwb@mail.nih.gov
    1. Year: 2010
    2. Date: Aug
  2. Journal: Bioorganic & Medicinal Chemistry
    1. 18
    2. 16
    3. Pages: 5925-5931
  4. Type of Article: Article
  5. ISSN: 0968-0896
  1. Abstract:

    In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N ',N ',N '',N ''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N, N ', N '', N '''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex (R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM (1) s (1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2) = 16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. Published by Elsevier Ltd.

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External Sources

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  2. DOI: 10.1016/j.bmc.2010.06.086
  3. View record in Web of Science®
  4. WOS: 000280664100015

Library Notes

  1. Fiscal Year: FY2009-2010
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