Characterization of continuously extruded iopromide-carrying liposomes forcomputed tomography blood-peal imaging

RATIONALE AND OBJECTIVES. Contrast-carrying liposomes are potentially usefu l as computed tomography (CT) blood-pool agents. In the present study, prel iminary safety, pharmacokinetics, and the CT imaging behavior of continuous ly extruded iopromide-carrying liposomes were studied. METHODS. Iopromide liposomes were prepared by continuous high-pressure extr usion. Cell membrane-damaging characteristics were assessed in vitro in dog erythrocytes, Acute and subchronic toxicity and pharmacokinetics parameter s were determined in rats. Computed tomography imaging efficiency was studi ed in rabbits. RESULTS. The iopromide-carrying liposomes caused only minor morphological c hanges in dog erythrocytes. The median lethal dose in rats was approximatel y 4.5 g of total iodine per kilogram of body weight. In a subchronic tolera nce study in rats that were administered six doses of 1 g iodine per kilogr am twice a week, no adverse effects were observed. The pharmacokinetics in rats was dose dependent, and elimination of iopromide was almost complete w ithin 7 days after intravenous administration. In rabbits, at a dose of 300 mg total iodine per kilogram, the iopromide-carrying liposomes displayed p rolonged blood circulation, with mean CT density differences >60 Hounsfield units (aorta) for up to 10 minutes. CONCLUSIONS. The iopromide liposomes were well tolerated, almost completely excreted, and have potential as a CT blood-pool imaging agent.