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Article

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

Supporting Info

Ankona Datta,^† Jacob M. Hooker,^† Mauro Botta,^‡ Matthew B. Francis,^†^§ Silvio Aime, and Kenneth N. Raymond*^†

Department of Chemistry, University of California, Berkeley, California 94720-1460, Dipartimento di Scienze dell'Ambiente e della Vita, Universit del Piemonte Orientale A. Avogadro, Via Bellini 25/G, 15100 Alessandria, Italy, Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, and Dipartimento di Chimica IFM, Universit di Torino, Via Giuria 7, 10125 Torino, Italy

J. Am. Chem. Soc., 2008, 130 (8), pp 2546–2552

DOI: 10.1021/ja0765363

Publication Date (Web): February 5, 2008

†

University of California.

‡

Università del Piemonte Orientale “A. Avogadro”.

Lawrence Berkeley National Laboratory.

Università di Torino.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, raymond@socrates.berkeley.edu

Abstract

High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a 5-fold increase in relaxivity, leading to a peak relaxivity (per Gd³⁺ ion) of 41.6 mM^-¹ s^-¹ at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2), and the NMRD fittings highlight the differences in the local motion for the internal (τ_Rl = 440 ps) and external (τ_Rl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.

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