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Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts

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Abstract

The need to develop target-specific MRI contrast agents to aid in disease characterization remains highly essential. In this study, we present a generation four polyamidoamine (PAMAM) folate-dendrimer that specifically targets the high affinity folate receptor (hFR) overexpressed on more than 80% of ovarian tumors. In vitro, mouse erythroleukemia cells expressing the hFR bind the radiolabeled folate-dendrimer chelate resulting in over 2700% increase in binding compared with untreated cells. The binding was inhibited by free folic acid to levels observed on folate-receptor-negative cells. In vivo, ovarian tumor xenografts resulted in a 33% contrast enhancement, following the folate-dendrimer chelate administration, that was significantly different compared with results obtained with a non-specific, extracellular fluid space agent, Gd-HP-DO3A. In addition, this contrast enhancement was absent in saline-treated animals, folate-receptor-negative tumors, and was inhibited by free folic acid. Results suggest that a macromolecular, dendrimeric MRI agent with high molecular relaxivities (1646 mM−1 s−1) can be used in specifically targeting the hFR on tumor cells and ovarian tumors.

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Author notes

  1. Erik C. Wiener

    Present address: 1710 Beckman Institute, 405 North Mathews, 6180L, Urbana, IL, USA

Authors and Affiliations

  1. Biomedical Magnetic Resonance Laboratory, College of Medicine, University of Illinois, Urbana, IL, USA

    Sheela D. Konda, Michael Aref & Erik C. Wiener

  2. The Beckman Institute, University of Illinois, Urhana, IL, USA

    Sheela D. Konda, Michael Aref, Steven Wang & Erik C. Wiener

  3. Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL, USA

    Sheela D. Konda & Erik C. Wiener

  4. Department of Nuclear, Plasma, and Radiological Engineering, University of Illinois, Urhana, IL, USA

    Michael Aref, Steven Wang & Erik C. Wiener

  5. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Martin Brechbiel

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  4. Martin Brechbiel
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Konda, S.D., Aref, M., Wang, S. et al. Specific targeting of folate–dendrimer MRI contrast agents to the high affinity folate receptor expressed in ovarian tumor xenografts. MAGMA 12, 104–113 (2001). https://doi.org/10.1007/BF02668091

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  • DOI: https://doi.org/10.1007/BF02668091

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