Photodynamic therapy, as the name implies, is the treatment of cancer by means of light. 4 It is a non-invasive form of therapy that is less harmful to the body than radiation, for example. The procedure involves injecting a photosensitive drug to the patient, which sensitizes cells to the effects of light. A beam of laser light is then focused on the tumor which kills the cancer cells. The technology has advanced in recent years with the introduction of small fiber-optic cables that direct the laser beam to tumors in more remote areas of the body. 1 5
How does the method work? The photosensitive molecule has the ability to absorb light energy and undergoes an internal rearrangement of its electrons to a triplet state. The triplet state molecule slowly transfers its energy to molecular oxygen to form highly reactive singlet oxygen. Singlet oxygen appears to kill cells primarily by its effect on the cellular structure known as the mitochondria. The mitochondria are responsible for energy production in the cell, and singlet oxygen shuts down the formation of the energy molecule ATP, which in turn is required for the vital processes of protein and DNA synthesis.
The "first generation" photosensitizer and its limitations
The first sensitizer to have clinical applications was a derivative of a molecular entity known as porphyrin, found in hemoglobin and chlorophyll. The drug is known as porfimer sodium, with the trade name of Photofrin. The product is approved by the Food and Drug Administration in cases of non-small cell lung cancer when the tumors are located in the bronchial lining. This procedure has been shown to very successful when the cancer is not too far advanced, and when surgery and radiotherapy are not indicated. The FDA has also approved the use of Photofrin to treat esophageal cancer and a precancerous skin cancer condition known as actinic keratosis. 3Clinical studies have shown that the procedure is very promising in early-stage cancers of the mouth, throat, larynx and bladder.
A major disadvantage in the use of Photofrin is that the drug remains in the cells of the skin and eyes, so patients who are treated must avoid bright light for about six weeks. Also, Photofrin is excited by red light at a wavelength that can only penetrate tissue to a depth of a few millimeters, making it unsuitable for the treatment of deep-seated tumors.
Second generation photosensitizers Meta-tetra hydroxylphenyl chlorine, known by the trade names of Foscan and Temporfin is chemically related to Photofrin, but has several advantages. It is excited at a longer wavelength, and achieves similar results to Photofrin at lower doses and shorter illumination times. After excitation, it stays a longer time in the triplet, thus producing more cytotoxic singlet oxygen. It also may be more selective between tumor and normal tissue. This product is currently in clinical trials for a large variety of cancers.
