Photodynamic Therapy (PDT) is a method of killing cells which utilizes a photosensitizing drug (usually a porphyrin of some type), light within the visible light spectrum of a wave length consistent with absorption characteristics of the specific sensitizer being used, and oxygen in tissues.
These 3 factors have to be together at the same time in the same place to have a biologic impact on cells. Because it depends on light, it can penetrate tissues only a few millimeters sparing what’s beneath. Red light is the most penetrating; this can be simply illustrated by the classic “experiment” of placing one’s fingers together over the head of a flashlight turned on; only red light gets through where the fingers come together.
If the photosensitizing agent is administered IV, it goes ubiquitously into virtually all cells. However, most normal cells appear to clear photosensitizers quickly, but most tumor cells appear to take much longer to clear them. Thus, if one times it right, the sensitizer, the laser controlled wave length of light, and the oxygen are together in tumor as opposed to normal tissues; and the biologic effects are largely limited to tumor and minimized in normal tissues. The one exception to this generalization is the skin. The basal layer of skin epithelium retains the sensitizer and as these cells slowly work their way to the surface (and to light exposure), they ultimately manifest cell death and severe skin reactions can occur. For this reason, skin protective measures to avoid light exposure must be employed for about 6 weeks after a photofrin injection. (Photofrin is the major PDT sensitizer for use in the USA. There are other photo sensitizers with more favorable pharmacokinetics, but they are generally considered investigational).
Most of the PDT throughout the world is aimed at relatively small non-melanomatous skin cancers, or GI surface lesions that can be approached by endoscopic techniques. At Penn, we are using PDT to “light up” the entire pleural cavity at the time of surgical resection for patients who have malignant miliary seeding of the pleural surface, which is generally considered an incurable condition.
PDT is nonionizing radiation therapy. Unlike ionizing X-ray therapy, DNA does not appear to be the target for PDT; membranes appear to be the target for PDT. PDT’s advantages are that it spares normal tissues far greater than other forms of cancer treatment and, because DNA is not its target, treatment induced cancer is unlikely to occur.
In practical terms, the only real limitation to the application of PDT for the treatment of cancer is the imagination required to get the light where it is needed. For this purpose, treatment at the time of surgery can dramatically expand its usage. Obviously the bright lights of the operating room are a potential problem but these can be neutralized by light filters placed on them. In many instances, light could be introduced directly into a tumor mass by interstitial techniques. This means inserting fibro-optic leads directly into a tumor mass by sterile techniques in the OR. This would be similar to earlier brachytherapy techniques from the 20th Century which are still in use today. The difference is that instead of inserting radio-active isotopes, fibro-optics would be inserted and hooked up directly to an appropriate laser light source. These kinds of approaches mean that PDT could be applied to breast, lung, prostate, bladder, head-and-neck, as well as a range of gastro-intestinal cancers.
PDT should not be considered as “the” answer for cancer treatment but rather part of the answer. In today’s world, optimal treatment is mixing and matching to an individual cancer patient’s problems.
