Paramagnetic polymerized liposomes as new recirculating MR contrast agents

Abstract

We describe a well-tolerated blood pool contrast agent with extended reclrculatory half-life based on paramagnetic polymerized liposomes (PPLs). PPLs were constructed from a new type of polymerizable lipid molecule that has a derivative of gadopentetate dimeghimine as the hydrophilic head group and diacetylene groups in the hydrophobia acyl chains, which cross-link when irradiated with ultraviolet (UV) light. Biodistributlon, blood pool half-life, and MR image enhancement were determined for PPLs composed of 10% of the gadopentetate dimeglumine lipid and 90% of ditricosadiynoyl tricosadiynayl phospha-tidylcholine (DAPC) at a dose of 0.015 mmnol 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 minutes after administration of the PPLs. Biodistribution studies using radiolabe-led 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 produced similar MR contrast enhancement of the blood pool as produced by other liposome contrast agents. However, the half-life of PPL elimination from the blood pool was prolonged relative to other liposome systems.