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.