PDT and Cancer
Although Photodynamic Therapy (PDT) has been used as a clinical treatment of cancer for more than 10 years in Canada, Europe and Asia, it is relatively new to the United States. In traditional PDT a drug or dye is administered to the patient either intravenously or by injection. The drug travels through the blood stream and localizes on cancer cells. After an appropriate time (24-78 hours) the localized drug is activated with light. The drug destroys the cancer cells, while leaving the normal tissue intact. The extent of this selectivity depends on the type of drug administered. The first drug to be accepted by the FDA was Photofrin (trademark). Photofrin is a clinic drug based on Heamatoporphoryn derivatives (HPD). Since that time a number of other drugs have been studied and have shown excellent results for the PDT treatment of cancers such as lung, skin, head, neck, throat, reproductive organs. New photodynamic drugs are currently being studied for treatment of brain cancer, breast cancer, and leukemia.

PDT and Age Related Macular Degeneracy
PDT currently being used to treat is used Age Related Macular Degeneracy (AMD). AMD is the leading form of blindness in people over the age of 50 and is becoming more and more prevalent as our population ages. AMD is caused by a growth of abnormal blood vessels over the central part of the retina, called the macular. PDT helps to stop and in many cases reverse the damage produced by AMD.

Recently the FDA issued Coherent Medical Group an approval letter for their Opthalmic laser developed for treatment of AMD. Coherent's new OPAL laser combined with a Verteporfin drug is currently under clinical trial.

PDT Mechanism
The accepted mechanism for PDT involves the interaction of an excited state of the drug or dye with the ground state of oxygen. A molecule of the drug absorbs a photon of red light and is excited to the first excited singlet state. If this singlet state is long lived energy can be transferred from the singlet state to the triplet state through interstitial crossing. This triplet state can react with local oxygen molecules created an excited state of oxygen called singlet oxygen.

Singlet oxygen is cytotoxic and destroys nearby cells. Since the drugs used in PDT are localized on cancer cells, this singlet oxygen reacts with the cancer cell.

There are two mechanism by which the singlet oxygen can attack a cell. In cancer treatments using PDT the drug is usually localized on the outside of the cell membrane, and the singlet oxygen destroys the microvascular of the cell, thus the dies due to lack of oxygen. Alternatively, if the dye is left for a longer period of time before light activation, the dye may permeate the cell membrane and attack the mitochondria of the cell, leading to programmed cell death or apotosis. This first mechanism, destruction of the microvascular is the most common, and is consistent with PDT efficacy for both cancer and AMD.

Two Photon PDT
The potential for two photon excitation in PDT has recently been demonstrated by the researchers at Photogen. Multiphoton excitation is made possible by using the high peak power of a femtosecond laser source. Two photon excitation allows low average power IR radiation to be used for excitation. This results in two key benefits: 1) deeper penetration depth of light; 2) new PDT treatments of skin melanoma without the addition of a drug or dye. This has been demonstrated by Photogen using the native optical absorbers (melanin).

Photogen Web site http://www.photogen.com

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