The design of liposomal paramagnetic MR agents: effect of vesicle size upon the relaxivity of surface-incorporated lipophilic chelates.

The 1/T1 NMRD profiles of lipid vesicles with the paramagnetic ion Gd attached via a chelate covalently linked to the membrane surface show a peak at approximately 20 MHz indicating that fluctuations of approximately 10(-8) s contribute to the form of the dispersion profile. If the correlation time for fluctuations of the paramagnetic chelate on the membrane surface is much less than the correlation time for rotation of the lipid vesicle, it would be expected that the measured 1/T1 relaxation rate for solvent protons should be invariant with vesicle size above a certain minimum vesicle diameter. We show that this is indeed the case for vesicles in the size range 50 to 400 nm average diameter and discuss general design considerations for the preparation of vesicle-associated MR contrast agents based upon paramagnetic chelates either trapped within the vesicle interior or attached to the membrane surface.