Liposome CT contrast tackles toxicity in liver

The Liposome Company released details of its CT contrast agenttechnology last month as patents pending in Europe were openedto public view. The Princeton, NJ, firm has agreed to work withGerman contrast supplier Schering to develop, manufacture andmarket a liposome encapsulated nonionic radiographic liver imagingagent (SCAN 2/13/91).

Schering will provide one of its nonionic contrast agents tofunction with the liposome technology. The Liposome Company willdevelop the encapsulated agent and hand it off to Schering forclinical trials and subsequent commercialization. The agent isnot expected to reach market until 1994 or 1995, said Marc J.Ostro, vice chairman and chief science officer of the U.S. firm.

The European patent filings relate to a liposome encapsulationtechnique called interdigitation-fusion. Liposome encapsulationof radiographic contrast has been tested in animal trials performedlargely in the U.S., he said.

The R&D firm initially applied its liposome technologyin therapeutic applications. Clinical investigations are underway in the U.S. for three of the firm's therapy agents. Imagingapplications of this technology were discovered almost by accident,Ostro said.

"This new (encapsulation) technology we developed allowedus to solve a problem that had been vexing scientists in the (liverimaging) area for a long time," he told SCAN.

Researchers had tried to develop particulate radiographic contrastmedia to improve CT contrast enhancement of liver tumors but raninto toxicity problems. Contrast developers eyed liposome encapsulationas a means around the toxicity problem but were unable to providesufficiently high iodine to lipid ratios for adequate contrastenhancement, Ostro said.

Liposomes have an advantage over other contrast delivery systems,such as perfluorocarbons, in their flexibility of design, he said.

"You can work your way around the issues that would causetoxicity in a static system," he said. "For instance,toxicity in the liver may depend on membrane fluidity, which,simply speaking, is lateral movement of lipids in the membraneof the liposome. The charge on the membrane is another factor,as is size. We can manipulate all these variables."

Other liposome contrast efforts have combined more lipid thaniodine in the agent, which has limited contrast enhancement. Workwith interdigitation-fusion, on the other hand, has resulted infour to six times as much iodine as lipid, Ostro said. The liposomeagent also stays in the liver for hours, compared to minutes withconventional liver agents, he said.

"Radiologists should be able to detect smaller metastasesand have the luxury of more time to do so," Ostro said.

While The Liposome Company is concentrating its imaging efforton radiographic contrast, the technology may also serve to deliverMR imaging agents to the liver in the future, he said.