J. Am. Chem. Soc., 125 (18), 5471 -5478, 2003. 10.1021/ja0340984 S0002-7863(03)04098-8
Web Release Date: April 12, 2003

Copyright © 2003 American Chemical Society

First Soluble M@C60 Derivatives Provide Enhanced Access to Metallofullerenes and Permit in Vivo Evaluation of Gd@C60[C(COOH)2]10 as a MRI Contrast Agent

Robert D. Bolskar,* Angelo F. Benedetto, Lars O. Husebo, Roger E. Price, Edward F. Jackson, Sidney Wallace, Lon J. Wilson, and J. Michael Alford

Contribution from TDA Research Inc., 12345 West 52nd Avenue, Wheat Ridge, Colorado 80033, the Department of Chemistry and the Center for Nanoscale Science and Technology, MS-60, Rice University, Houston, Texas 77251-1892, and the MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Boulevard, Houston, Texas 77030-4009

bolskar@tda.com

Received January 9, 2003

Abstract:

M@C60 and related endohedral metallofullerenes comprise a significant portion of the metallofullerene yield in the traditional arc synthesis, but their chemistry and potential applications have been largely overlooked because of their sparse solubility. In this work, procedures are described to solublize Gd@C60 species for the first time by forming the derivative, Gd@C60[C(COOCH2CH3)2]10, and its hydrolyzed water-soluble form, Gd@C60[C(COOH)2]10. Imparting water solubility to Gd@C60 permits its evaluation as a magnetic resonance imaging (MRI) contrast agent. Relaxometry measurements for Gd@C60[C(COOH)2]10 reveal it to possess a relaxivity (4.6 mM-1 s-1 at 20 MHz and 40 C) comparable to that of commercially available Gd(III) chelate-based MRI agents. An in vivo MRI biodistribution study in a rodent model reveals Gd@C60[C(COOH)2]10 to possess the first non-reticuloendothelial system (RES) localizing behavior for a water-soluble endohedral metallofullerene species, consistent with its lack of intermolecular aggregation in solution as determined by light-scattering measurements. This first derivatization and use of a M@C60 species suggests new potential for metallofullerene technologies by reducing reliance on the chromatographic purification procedures normally employed for the far less abundant M@C82 and related endohedrals. The recognition that water-soluble fullerene derivatives can be designed to avoid high levels of RES uptake is an important step toward fullerene-based pharmaceutical development.

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