Liposomes as carriers for paramagnetic gadolinium chelates as organ specific contrast agents for magnetic resonance imaging (mri)

Abstract

Small unilamellar liposomes were used as carriers for chelates of gadolinium as organ specific magnetic resonance imaging (MRI) contrast agents. The pharmacokinetic and imaging properties of the lipophilic liposome membrane associated chelate diethylenetriaminepentaacetate-stearylamide (DTPA-SA) were investigated. Gadolinium-DTPA-SA liposomes accumulated in the liver of rats at a peak concentration of 60% of the injected dose 4 hours after application. The elimination half-life from the liver was 61 h. Tl-weighted MR images of this liposomal Gd-chelate in rats and dogs gave a strong signal enhancement of the abdominal organs, liver and spleen. High blood concentrations of the Gd-DTPASA liposomes, reaching 60% of the injected dose after 30 min., decreasing to 40% after 2 hours, suggest their potential as a contrast agent for the blood pool. The gadolinium chelate benzoyloxypropionictetraacetate (Gd-BOPTA) was entrapped in liposomes of different lipid composition. Pharmacokinetic studies of liposome preparations containing a poly(ethylene)glycol (PEG) modified lipid showed that high levels of 80 - 60 % of the injected dose remained in the blood, 15 to 60 minutes after application. Peak blood concentrations of liposomes without PEG reached only 30%, with a correspondingly higher uptake in the liver and the spleen. Thus, both the lipophilic chelate Gd-DTPA-SA, as well as Gd-BOPTA entrapped within the aqueous volume of liposomes possess not only a potential as a liver and spleen specific contrast agent, but also for the imaging of the vascular system.