Photodynamic therapy is a promising type of experimental treatment for cancer that uses light to destroy cancer cells. The technique is based on the discovery that certain light-sensitive chemical compounds called photosensitizers are preferentially taken up by cancer cells in the body. When light is shone on cancer tissues containing such compounds, a chemical reaction ensues which results in the death of cancer cells. Since the photosensitizer is not taken up so effectively by non-cancerous cells, normal tissues are less affected by the treatment. In this way, cancer tissue can be selectively destroyed with a minimum of damage.

PDT is not a new technique. The essential principle was discovered in Germany in the late 19th century and the first patients were successfully treated over 100 years ago. However, for various reasons PDT has remained on the fringe of conventional medical practice. For example, there were only five presentations on PDT at the 2004 meeting of the American Society of Clinical Oncology (ASCO). By contrast, there were thousands of presentations on the topic of chemotherapy.

The photosensitizing drug Photofrin is approved by the Food and Drug Administration (FDA) for the treatment of several kinds of cancer, including superficial skin cancers and some cancers of the esophagus and lung. However, Photofrin is not sufficiently sensitive for many important applications, and a worldwide search is under way for a second or even third generation photosensitizer to replace Photofrin. A few other agents are already approved in Europe and the East.

Dr. Harry Morrison, a professor of chemistry and former dean of Purdue University's School of Science, has now developed a group of new photosensitive compounds based on rhodium, a rare metal similar to platinum. These new rhodium-based compounds are not only potential candidates for use in PDT but can also be used to deactivate the Sindbis virus, a type of virus closely related to the West Nile and yellow fever viruses. According to a press release from Indiana University, "Cancer and viruses may someday find themselves blinded by the light of therapies" (Boutin 2004). While actual treatments based on this discovery are still several years away, "the compounds could have potential as anticancer agents and for blood sterilization" (ibid).

"We have proven in principle that light and chemistry together can destroy tumor cells and the Sindbis virus," said Dr. Morrison. "This research offers hope that someday we may be able to replace standard chemotherapy drugs with others that are far less generally harmful to a patient's body and guarantee safe, sterile blood for transfusions."

Platinum-based compounds such as cisplatin and carboplatin are prominent among chemotherapy drugs and form the basis of many chemotherapy regimens. These compounds are known to bind cellular DNA (genetic material), thereby rendering cells unable to reproduce. This effectively destroys cancer cells, but its effect is non-selective: in the process of killing cancer cells, platinum-based drugs also kill many normal cells in the body.

"That's the reason cancer patients often lose their hair," Morrison said. "Hair cells, like many others in the patient's body, are also destroyed by these platinum-based chemotherapy drugs." So physicians and researchers have long sought other, more controllable and selective ways of killing cancer cells. "If we had a drug we could activate when it reached a certain place in the body – and nowhere else – it would reduce the stress on the rest of a cancer patient's system," said Morrison.

The Purdue group tried several different chemical complexes in which rhodium was substituted for platinum. Although in the platinum family, rhodium is a separate element (#45 in the Periodic Table) and is named after the rose-like color of its salts. ("Rhodon" in Greek means rose.)

Eventually the Indiana scientists found one compound that was able to damage DNA in living cells in much the way that platinum does, but with one important difference: it remained inert – and therefore harmless - until it was activated by an ultra-violet A (UVA) light beam.

"Anticancer therapies could, in theory, be developed using such photo-activated rhodium complexes," Morrison said. "The interior of the body is dark, but it might be possible to thread a fiber-optic cable through the arteries and flood a tumor with light. Some lasers are also capable of shining through tissue without damaging it, and they might also be candidates for light delivery." In fact, experimentally, lasers are already being used to delivered powerful beams of light not just intra-arterially, as Dr. Morrison suggests, but by various other means as well.

The compound – known by the acronym 'DPPZPHEN' (itself an abbreviation of its long chemical name)—has also shown potential as an antiviral or blood sterilizing agent. That is because it is lethal to any nucleic acid it encounters, including the RNA found in some viruses.

"Since [red] blood cells and platelets do not themselves have nucleic acid, they are safe from the compound," Morrison said. "But it is potentially possible to purify blood of foreign organisms and viral particles using the rhodium complex and light exposure before it is used in transfusions. It could make for a safer blood supply."

Each of these applications, however, is still years from development, Morrison cautioned. "We have only proven in principle that such therapies are possible," he said. "Our experiments have only been on tumor cells in the laboratory, not in living animals. It will require further research to determine how rhodium-based drugs could be created."

"Another issue is how to keep these compounds from getting scavenged up by the blood before they reach their targets, which tends to happen because of their adhesion to blood proteins, Morrison continued. "But I believe the results are promising for the future of the fight against cancer and viruses, and I hope other groups will continue the work we have begun."

TO BE CONCLUDED, WITH REFERENCES AND RESOURCES, NEXT WEEK

--Ralph W. Moss, Ph.D.