Gadolinium-Loaded Viral Capsids as Magnetic Resonance Imaging Contrast Agents

Polymeric nanohybrid P22 virus capsids were used as templates for high density Gd³⁺ loading to explore magnetic field-dependent (0.5-7.0 T) proton relaxivity. The field-dependence of relaxivity by the spatially constrained Gd³⁺ in the capsids was similar when either the loading of the capsids or the concentration of capsids was varied. The ionic longitudinal relaxivity, r₁, decreased from 25-32 mM^-1 s^-1 at 0.5 T to 6-10 mM^-1 s^-1 at 7 T. The ionic transverse relaxivity, r₂, increased from 28-37 mM^-1 s^-1 at 0.5 T to 39-50 mM^-1 s^-1 at 7 T. The r₂/r₁ ratio increased linearly with increasing magnetic field from about 1 at 0.5 T, which is typical of T₁ contrast agents, to 5-8 at 7 T, which is approaching the ratios for T₂ contrast agents. Increases in electron paramagnetic resonance line widths at 80 and 150 K and higher microwave powers required for signal saturation indicate enhanced Gd³⁺ electron spin relaxation rates for the Gd³⁺-loaded capsids than for low concentration Gd³⁺. The largest r₂/r₁ at 7 T was for the highest cage loading, which suggests that Gd³⁺-Gd³⁺ interactions within the capsid enhance r₂ more than r₁.