Comparative evaluation of two membrane-based liposomal MRI contrast agents.

Two phospholipids--one bearing a nitroxide free radical covalently attached to its polar headgroup, and the other bearing a similarly attached chelating agent with bound gadolinium--were compared in vivo as liposomal contrast agents for MR imaging. In each case the phospholipid contrast agent was incorporated into the membranes of sonicated unilamellar vesicles. The agent with bound gadolinium proved to be considerably more potent at highlighting regions of liposome biodistribution than did its spin-labelled analogue. Injected intramuscularly into rats, the spin-label liposomes produced local tissue contrast that persisted for 1 h; while under similar conditions, the liposomal gadolinium persisted for over 24 h. By comparison, water-soluble, nonliposomal DTPA-Gd3+ (dimeglumine), was rapidly cleared from the same intramuscular sites--appearing in kidney bladder within 15 min of injection. When delivered intravenously, maximum effect from both liposomal agents was observed in liver and spleen within 1-2 h, although the spin-label agent produced only marginal contrast. The concomitant use of fat suppression proved a valuable adjunct to liposomal contrast for imaging organs of the reticuloendothelial system.