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 μM. The T₁ and T₂ 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. Magn Reson Med, 2005. Published 2005 Wiley‐Liss, Inc.