Power Imaging System Merges Diagnostics, Therapeutics
By Don Long
Staff Writer
Astar trek-type medicine has given us a look at the ultimate in noninvasive health care: A hand-held device is passed over the patient and—voila!—he is able to return to his station on board the Enterprise. Whatever that device is, it is capable of both diagnosing and treating the injury or disease at one and the same time.
Combining the two modalities—let alone being able to do it noninvasively—is of course in the far future of health care. But it could be closer than we might think, given the proof of that concept in a new system from Photogen Technologies, of Knoxville, Tenn, a company focused on developing various leading-edge systems, in tandem. Its primary focus thus far has been phototherapeutics, that is, the combination of light with drugs for treating tissue diseases, with the announcement this week that it has received five international patents covering its Two-Photon Excitation system for treating cancer.
Growing from work in this area, Photogen earlier this year also announced the development of a two-photon diagnostic technology, an infrared light system that offers the possibility of noninvasive but even more precise imaging within the body, and potentially able to deliver therapy to the cells identified for treatment either with or without radiosensitive agents.
That is one of the advanced goals described by Photogen Senior Scientist Eric Wachter, PhD, who says the two-photon system offers the possibility of sidestepping biopsy while providing treatment "within a few centimeters, fairly near the surface."
"Key to this system is the wavelength of photons," he says. "The wavelength of the photon allows it to be delivered beyond just superficial portions of the body. In these very short pulses, we can produce the two-photon process very efficiently without risking any other sort of tissue-photon interaction to [healthy] tissues of the body."
"What we’re doing is taking a beam and focusing it down to a very small volume," he said, with the two photons becoming "coherent, both temporally and spatially—they’re present at the same time and they have the same trajectory, the same phase."
"It sounds pretty exotic," Wachter acknowledged. "What it means is that [the pulses] originate from a single laser pulse and a laser is by definition producing coherent light, by focusing that light."
A key advantage Wachter cited for the system is its ability to produce clear images in the presence of various distracting artifacts, such as other light. Standard photon microscopy normally requires a "catastrophically dark room, totally sealed off, to collect very beautiful images. But if you allow any small amount of light into the system, the performance degrades very quickly," Wachter said. But with the two-photon system, "you can literally turn on overhead fluorescent lights and obtain data not markedly different than the profoundly dark conditions."
Using a basic analogy, Wachter compared this new imaging system to a common radio transmission. "With AM radio," he said, "we’re able to extract very small radio frequency signals out of the atmosphere in the presence of a tremendous amount of noise." This advantage translates well to both research and clinical arenas, according to Wachter.
On the clinical side, two-photon imaging—and, more generally, multi-photon imaging—is being pushed forward by David Piston, PhD, a professor of biophysics at Vanderbilt University in Nashville, Tenn, who first worked on developing multi-photon imaging in a collaboration with two of his graduate students.
This type of imaging, Piston says, is best for "thick tissue work, something other imaging systems can’t do. We use it to look at auto flurescene in the liver, pancreas and peripheral tissue, to look at metabolic state of the cells."
The limiting factor, he says, is determining when to use this imaging modality. "It can’t do that much on a whole animal scale," he says, "but you can get an order of magnitude and better resolution than PET [positron emission tomography] or NMR [nuclear magnetic resonance] or anything like that. But you have to figure out when you need that betterness.’ That’s where we are now."
Clinically, he predicts the most frequent uses in diagnosing skin cancer and other skin diseases, plus, in hard tissue uses, dental applications.
This latter is being developed by John Girkin, a professor at the University of Straphclyde (Glasgow, Scotland), according to Wachter, who says that this research may result in the commercialization of a two-photon imaging system for this application in 2-3 years.
The ultimate use of the system would come in combination with the company’s phototherapeutic products, as represented in its Two-Photon Excitation system. Two treatment patents for that system have been announced in Australia and Singapore, and three imaging patents have been issued in Australia, Singapore, and New Zealand. The technology is also covered by various U.S. patents.
Two-photon imaging could ultimately be used to help determine when to use phototherapy, and since the systems for delivering laser light are essentially the same in both the diagnostic and phototherapeutic applications, they could then be combined into one system. "The general apparatus would be virtually identical," said Wachter, "so you have the potential for a modality where you would be able to diagnose and treat with a single unit."
Wachter reported that Photogen is in the process of preparing various clinical trials of its phototherapeutic agents in treating cancers of the breast and for melanoma. And he said that the company should be able to bring its microscopy product to the market "about the same time as the therapeutic product. We’re very excited about the prospects."
"We’re still in the learning phase of how to get from the laboratory to the market," he added, "but these are some very good-looking technologies."
Besides acceleration of the company’s development of a compound for treating cancer, President and CEO Taffy Williams reported progress in a joint venture with Elan to develop N1177, a minimally invasive lymphography product used to diagnose metastatic tumors in lymph nodes. "We expect to commence one or more Phase II studies for this product in 2001," Williams says.
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