Multiparametric MRI characterization of magnetic viral complexes

Magnetic nanoparticles (MNPs) can be used as carriers for magnetic drug targeting [1]. When assembled with oncolytic viruses they are a promising tool for cancer treatment. Spatial distribution of particle concentration and aggregation state of the MNP-virus-complexes in the tissue of interest can be assessed by MRI relaxometry allowing for non-invasive therapy monitoring. We investigated the influence of the assembling of MNPs with adenoviruses (Ad) on MRI relaxation rates.

PEI-Mag2 nanoparticles were assembled with oncolytic adenovirus as described in [2]. Dilution series of free particles and magnetic viral complexes were prepared and measured on a 3 Tesla whole body imaging system. R₁, R₂ and R₂* maps were measured using spin echo inversion recovery, spin echo and multi-echo gradient echo sequences. Signal intensities were least-squares fitted for each voxel.

The figures show the relaxation rates of the dilution series with linear fits. Relaxivities for the free particles were r₁ = 1.5 ± 0.1 mM^-1s^-1, r₂ = 414 ± 18 mM^-1s^-1, r₂* = 532 ± 26 mM^-1s^-1 and for the magnetic viral complexes r₁ = 1.45 ± 0.05 mM^-1s^-1, r₂ = 318 ± 10 mM^-1s^-1, r₂* = 483 ± 14 mM^-1s^-1.

The r₁ and r₂* relaxivities do not change significantly within the error margins when the particles form complexes with the viruses. Therefore R₂* relaxation rates seem best suited for particle quantification after a calibration step, whereas R₁ rates are too low for good contrast. However, r₂ relaxivity decreases when the complexes are formed, probably because of partial refocusing [3]. This indicates, that r₂ measurements can be used to determine the aggregation state of the complexes.