In vivo EPR spectroscopic imaging for a liposomal drug delivery system.

We used the membrane-impermeable nitroxyl radical 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyliodide (CAT-1) as a model drug encapsulated in liposomes in order to separately map the 2D distribution of both liposomal-encapsulated CAT-1 and free CAT-1. Phantoms were prepared with a CAT-1 solution and a liposomal CAT-1 suspension. Spectral-spatial images were obtained along several polar-arranged spatial axes through the phantom. The 1D spatial distributions (projections) of each signal component, reflecting the concentration of CAT-1, were then extracted from the spectral-spatial images. 2D EPR images of liposomal-encapsulated CAT-1 and free CAT-1 were separately reconstructed from the resulting projection data sets. 2D mapping of each component exhibited good agreement with respect to the phantom. Separate maps were generated from separate injections of free CAT-1 and liposomal CAT-1 injected into the femoral muscle of a living mouse. The EPR signal of the free CAT-1 gradually decreased during data acquisition. Because of this decay, we calibrated the image intensity by extrapolating the signal intensity to that detected at the beginning of data sampling. Both the position and size of the individual images were in very good agreement with those of the mouse thigh obtained by MRI.