Paramagnetic viral nanoparticles as potential high-relaxivity magnetic resonance contrast agents

Abstract

In order to compensate for the inherent high threshold of detectability of MR contrast agents, there has been an active interest in the development of paramagnetic nanoparticles incorporating high payloads of Gd3+ with high molecular relaxivities. Toward this end, the protein cage of Cowpea chlorotic mottle virus (CCMV), having 180 metal binding sites, is being explored. In vivo CCMV binds Ca2+ at specific metal binding sites; however, Gd3+ can also bind at these sites. Using fluorescence resonance energy transfer we have characterized the binding affinity of Gd3+ to the metal binding sites by competition experiments with Tb3+. The measured dissociation constant (K-d) for Gd3+ bound to the virus is 31 mu M. The T-1 and T-2 relaxivities of solvent water protons in the presence of Gd3+-bound CCMV were 202 and 376 mM(-1) s(-1), respectively, at 61 MHz Larmor frequency. The unusually high relaxivity values of the Gd3+-CCMV are largely a result of the nanoparticle virus size and the large number of Gd3+ ions bound to the virus. These preliminary results should encourage further investigations into the use of viral protein cages as a new platform for MR contrast agents.