GE Healthcare searches for ways to pull profit from hyperpolarization

The future for hyperpolarized gases couldn't have been brighter in the late 1990s. Helium and xenon promised to go where no other MR contrast agent could: the lungs. With a dozen drugs being developed to treat chronic obstructive pulmonary disease and prevalence of lung disease high in developed nations, largely due to cigarette smoking, this new technology had "winner" written all over it. Or so it seemed.

Today GE Healthcare, which owns the technology through its acquisition of Amersham, is in a quandary over what to do with it. The company is planning a summer meeting of luminaries, some of whom have devoted much of their professional lives to developing the clinical side of this technology, hoping to get ideas from them about where to take it.

At the Miami meeting of the International Society for Magnetic Resonance in Medicine, GE executive Jonathan Allis, Ph.D., vice president of technology for medical diagnostics at GE Healthcare, framed the question to the hyperpolarized media study group in capitalistic terms.

"We would like to make some money out of this, as we have already spent a lot," Allis said.

The greatest opportunity may be less in the pulmonary applications that first excited the imaging community than in the possibilities presented by the infusion of liquid formulations, specifically those made of hyperpolarized carbon and nitrogen. Compounds fashioned from these elements could be to MR what FDG is to PET: the tools for plumbing the molecular depths of disease.

"The carbon stuff is immensely exciting," Allis said. "The possibility of developing an MR kind of FDG could lead to a potentially huge future market."

It is sobering, however, to recognize that unknowns now serve as the foundation for much of the appeal associated with hyperpolarized technology - much as they did five years ago. At the beginning of this decade, Amersham executives predicted that 400,000 doses of hyperpolarized gas would account for Amersham revenues of $100 million by 2006. Making these gases all the more attractive was their ability to produce excellent images using low-field scanners.

Allis bought into this prediction as an Amersham executive five years ago. Now, as a GE executive, he would be happy to get even a small slice of that pie. His remark that GE has only one year left to reach its predicted annual revenues of $100 million from the technology sent a grudging chuckle through the room of luminaries.

"We had thought this would be a great way to make a lot of money, but it rapidly evolved into a great way to spend a lot of money," he said.

The commercial bottom dropped out of hyperpolarized technology because of a collision of practical challenges, regulatory changes, and pharmaceutical misfortunes.

The production of these agents was always problematic. Hyperpolarized nuclei, like PET radioisotopes, decay quickly, leading to a logistical nightmare in getting the gases to customers. Early development of helium as an imaging agent was problematic in itself, as the supply of this element is limited and therefore expensive.

Regulatory concerns entered the picture in 1999, when the FDA reclassified hyperpolarized noble gases as drugs. The real kicker, however, was the failure of proposed therapeutic agents to treat pulmonary diseases, which left the medical community with an excellent diagnostic but no way to affect clinical outcome.

GE has had some success on the in vitro side, licensing the technology for hyperpolarizing carbon and nitrogen to Oxford Instruments. The U.K.-based company has since launched a product, called HyperSense, for use in NMR spectroscopy. GE is now examining how hyperpolarized gases, particularly xenon, might be used as biomarkers to assist pharmaceutical firms in their development of therapeutic agents.

Of greater interest to the company are developments involving other nuclei. One is the linking of hyperpolarized carbon-13 to materials that naturally occur in the body, forming a contrast agent that allows MR perfusion studies. Another is the use of hyperpolarized C-13 as a molecular imaging agent to examine enzyme metabolism in the body.

Early clinical studies of this application are scheduled to begin this summer. Allis is hopeful, but exceedingly cautious.

"The things that are far away are always exciting," he said. "The closer you get, the less interesting they become. Who knows how exciting C-13 will look in five years?"