MRI/21inches/1stjc/mike1st

By ELIZABETH HAYES

Staff Reporter

A Tucson, Ariz.-based technology development firm is betting millions that a Caltech chemist's invention will revoultionize magnetic resonance imaging and turn a profit.

With magnetic resonance imaging, or MRI, technicians use low energy pulses to generate a three-dimensional image of a patient's brain or other body parts. The images can help doctors diagnose illness or injury.

Tom Meade, a chemist at the California Institute of Technology, came up with a special magnetic dye that, when injected into a patient, imparts more-detailed information, helping doctors to better diagnose diseases in potentially any organ.

Meade and two colleagues Scott Fraser and Russell Jacobs began their MRI research six years ago at Caltech's Beckman Institute. Sensing profit potential, Meade two years ago used a "grubstake" grant from the school's technology transfer office to prove the concept's practical application.

"It was clear to us we had a very important discovery, if we could incubate it somehow to a level that would be attractive to a big pharmaceutical outfit," Meade said.

The technology transfer office hooked up with Tucson-based Research Corporation Technologies, which periodically visits the school to scout for technologies with commercial potential and then manages them.

RCT funded Meade's research last year, he said. But because academia is not the place to take a discovery to the marketplace, Meade founded Pasadena-based MetaProbe LLC which is now co-owned by RCT, Caltech and the three Caltech inventors. MetaProbe hopes to eventually partner with a large pharmaceutical company to sell the dye to hospitals and clinics that use MRIs.

The majority stake in MetaProbe is owned by RTC, with Caltech owning a smaller stake and Meade and his colleagues owning the smallest interest. In addition to their equity stakes, Caltech and the three inventors will receive royalties based on sales.

"In my mind, there have not been many quantum leaps in the MRI (dye) area and this represents a quantum leap," said Jeff Jacob, director of RCT's venture development group. "This will play an important role in physicians treating patients."

He estimates the market could be in the hundreds of millions of dollars per year.

"It is the holy grail to do functional imaging," Jacob said.

RCT would not disclose how much it has contributed to the venture, although Jacob said it has been less than $1 million so far. RCT manages the company and has the license for the invention.

"We put in the technology and they put up the cash," said Larry Gilbert, Caltech's director of technology transfer.

Meade said his motivation was two-fold: altruistic and to raise money for his lab at Caltech.

"Federal funding is drying up. It's harder to get grants. If my funding is drying up, I'll do anything to fund my research. Collaborating with a corporate entity is not a bad thing," Meade said.

MetaProbe will pursue a corporate partner to help usher the dyes through FDA approval, obtain a product license and market and sell them to hospitals and centers that use MRI for diagnoses. More clinical studies also have to be done.

Gilbert said it could be another five to seven years before it is used in humans.

The applications are numerous, but Meade see four markets to start with: diagnosing diseases in the brain and heart, monitoring drug therapy in cancer patients, for example and tracking the reconstruction of joints and tissue in physical therapy.

"The better the diagnosis, the better the treatment," which means decreased health costs, Gilbert said.

Scientific applications include studying brain function and monitoring genes. Meade already is using the invention with embryos as they develop in tadpoles and small primates.

The key is something called a "contrast agent," which is akin to a fluorescent dye. Think of Roto-Rooter, which flushes dye down the toilet to find the source of a leak in the pipes.

Magnetic-resonance dyes are currently used in MRIs to determine the type and scope of any injury in which the circulatory system is damaged. For example, they can help pinpoint a rupture in someone who suffered a blunt trauma to the head, or delineate a tumor in more detail.

But Meade innovated a new class of "smart" dyes that respond to various enzymes in the body and report on the metabolic state of cells. One seeks out a specific type of cell and another stays dark on the image until some metabolic or physiological event of the scientist's or doctor's choosing lights it up.

Meade's invention could be used to tell the difference between dead or constricted but salvageable heart tissue, or between dead or cancerous cells. It could also aid diagnosis of the early stages of Alzheimer's disease vs. manic-depression, which are sometimes hard to distinguish in a clinical interview.

"You can map brain function at the cell level in an MRI image," Meade said.

If a patient is suffering from liver disease, an ordinary contrast agent would only reveal whether the organ is swollen or abnormal looking. A smart agent keyed to an important liver enzyme would indicate how well the cells are functioning.

"It's a huge leap of technology," Meade said.

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