Preparation of a modified Gd-DTPA complex : a potential contrast agent for magnetic resonance imaging

Magnetic Resonance Imaging (MRI) of the liver and spleen has yet to equal the quality of MRI generated from the central nervous system. Gd-DTPA Is very effective at reducing the spln-lattlce relaxation times of the hydrogen in cellular water and is thus a good contrast enhancing agent. However, Gd—DTPA Is not tissue specific and Is Indiscriminately distributed throughout the vascular system of most tissues. The subject of this thesis Is the development of a Gd-DTPA derivitive that accumulates specifically in the liver and spleen and reduces the spin-lattice (T₁) relaxation times of those organs.

DTPA was covalently linked to stearylamine and the resultant ligand was complexed to gadolinium Ions to form a paramagnetic phospholipid analog. The new complex was Incorporated Into the lipid bilayer of liposomes as a means for delivery. Normal Balb/c mice received Intravenous Injections of the liposomal suspensions and the spin-lattice relaxation times of the liver and spleen were measured vitro. The relaxation rates of the livers and spleens were Increased by 100 and 67%, respectively, within 30 minutes after administration of 14 μmoles of lipld/mouse (0.22 mmole Gd/kg). Biodistribution studies revealed that, within 30 minutes, 44% of the Injected dose accumulated in the liver and 12% In the spleen. After 24 hours, 70% of the administered dose appeared in the liver compared to 21% In the spleen.