Web Release Date: February 5,
High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nanosized MRI Contrast Agents1
and
Department of Chemistry, University of California, Berkeley, California 94720-1460, Dipartimento di Scienze dell'Ambiente e della Vita, Università 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, Università di Torino, Via Giuria 7, 10125 Torino, Italy
Received August 29, 2007
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 (
Rl = 440 ps) and external (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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