Schering, Brookhaven ink development relationship

In the quest to further refine radiographic contrast imaging, Schering and the U.S. Department of Energy’s Brookhaven National Laboratory have signed an agreement to codevelop a new x-ray imaging method. Schering and Brookhaven expect their collaboration to produce a contrast agent that can better take advantage of the high-energy end of the x-ray spectrum, therefore reducing the radiation dose required and producing higher-resolution images. A device that can select the x-rays that are best absorbed by the contrast agent will also be designed.

Schering’s part of the agreement is to develop an x-ray contrast agent based on a heavier element than iodine, which is used in most injectable radiography contrast agents. By using an element such as gadolinium, the agent should be more efficient at absorbing the high-energy end of the x-ray spectrum, and should reduce the risk of allergic reaction associated with iodine for some patients, according to Dr. Avraham Dilmanian, medical physicist at Brookhaven. Gadolinium has been used effectively in MRI, but these MRI agents are not concentrated enough for x-ray imaging.

“Schering will develop the same kind of agent being used for MRI, but will increase the density of the gadolinium in the agent. Since iodine isn’t very heavy, the amount of iodine used in x-ray imaging today is quite large,” Dilmanian said. “And iodine is chemically quite active. Both these factors cause some patients to have adverse reactions to the contrast agent, and so there are some people who are excluded from imaging procedures with iodine because they are at risk. We hope to address this problem by developing an agent that is safer than iodine, and more effective.”

As Schering develops the agent, Brookhaven will develop a device that will select this narrow x-ray range and that can be used with conventional x-ray sources, according Dilmanian. Brookhaven plans to explore two methods in its device development: a crystal monochromator, which selects x-rays in an energy range that is best absorbed by an element such as gadolinium, and beam filtration, which filters out the lower part of the x-ray spectrum.

Schering will develop its agent at its facilities in Germany, while Brookhaven will develop its device at its headquarters in Upton, NY. The two entities will test Schering’s agent prototype using narrow-energy spectra x-rays at Brookhaven’s National Synchroton Light Source (NSLS). They will also test Schering’s agent with Brookhaven’s device at the State University of New York at Stonybrook’s radiology department. The research will be conducted with phantoms or animals; Schering and Brookhaven have no plans to initiate human trials as part of this particular R&D agreement.

Berlin-based Schering approached Brookhaven four years ago, after Schering researchers read papers on the DOE’s work on a CT scanner that uses narrow-energy spectra. The partnership began in August 1999, and will stretch over three years. Both Schering and Brookhaven will fund their own research.

If Schering and Brookhaven are successful in their efforts to prove to the clinical community that Schering’s agent is dense enough for use with high-energy x-rays and that Brookhaven’s device is efficient enough to select that x-ray range, the remaining challenge facing the technology’s introduction to the market for use with patients will be to encourage x-ray manufacturers to develop more intense x-ray tubes that can handle this kind of imaging, according to Schering.

“Improving the characteristics of x-ray beams toward mono-energy would reduce the radiation load, and could also potentially increase the sensitivity and specificity of this technique,” said Frank Richtersmeier, Schering spokesperson. “The technique could be further improved if dedicated contrast agents tailored for special x-ray beams were available. But a big hurdle is the fact that dedicated x-ray machines with narrow-energy bandwidth are not available for routine investigation. The outcome of our research may convince the industry to develop such devices.”