PARAMAGNETIC POLYMERIZED LIPOSOMES AS NEW RECIRCULATING MR CONTRAST AGENTS

We describe a well-tolerated blood pool contrast agent with extended r ecirculatory half-life based on paramagnetic polymerized liposomes (PP Ls), PPLs were constructed from a new type of polymerizable lipid mole cule that has a derivative of gadopentetate dimeglumine as the hydroph ilic head group and diacetylene groups in the hydrophobic acyl chains, which cross-link when irradiated with ultraviolet (UV) light. Biodist ribution, blood pool half-life, and MR image enhancement were determin ed for PPLs composed of 10% of the gadopentetate dimeglumine lipid and 90% of ditricosadiynoyl tricosadiynayl phosphatidylcholine (DAPC) at a dose of 0.015 mmol Gd+3/kg in rats, In T1-weighed MR images (TR/TE = 400/18 msec), an average signal enhancement of 34% in the kidneys and 20% in the liver was observed, which persisted for at least 90 minute s after administration of the PPLs, Biodistribution studies using radi olabeled PPLs confirmed that 80% of the injected dose remained in the blood pool after 2 hours, The half-life of elimination from the blood pool was 19 hours. The preparation was well tolerated in rats and prod uced similar MR contrast enhancement of the blood pool as produced by other liposome contrast agents, However, the half-life of PPL eliminat ion from the blood pool was prolonged relative to other liposome syste ms.