High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

Journal Article · Wed Aug 29 04:00:00 EDT 2007 · Journal of the American Chemical Society

OSTI ID:926163

Meux, Susan C; Datta, Ankona; Hooker, Jacob M; Botta, Mauro; Francis, Matthew B; Aime, Silvio; Raymond, Kenneth N

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 five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -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 (1) there is facile diffusion of water to the interior of capsids and (2) 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 ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 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.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: Materials Sciences Division
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 926163
• Report Number(s): LBNL-95E
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Vol. 130; ISSN JACSAT; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
CHELATES
DIFFUSION
GADOLINIUM
Gadolinium Hydroxypyridonate MRI NMRD
MODIFICATIONS
PROTONS
RELAXATION
WATER