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Photodynamic Therapy Photodynamic therapy (PDT), matured as a feasible medical technology in the 1980s at several institutions throughout the world, is a third-level treatment for cancer involving three key components: a photosensitizer, light, and tissue oxygen. It is also being investigated for treatment of psoriasis, and is an approved treatment for wet macular degeneration. Mechanism of action A photosensitizer is a chemical compound that can be excited by light of a specific wavelength. This excitation uses visible or near-infrared light. In photodynamic therapy, either a photosensitizer or the metabolic precursor of one is administered to the patient. The tissue to be treated is exposed to light suitable for exciting the photosensitizer. Usually, the photosensitizer is excited from a ground singlet state to an excited singlet state. It then undergoes intersystem crossing to a longer-lived excited triplet state. One of the few chemical species present in tissue with a ground triplet state is molecular oxygen. When the photosensitizer and an oxygen molecule are in proximity, an energy transfer can take place that allows the photosensitizer to relax to its ground singlet state, and create an excited singlet state oxygen molecule. Singlet oxygen is a very aggressive chemical species and will very rapidly react with any nearby biomolecules. (The specific targets depend heavily on the photosensitizer chosen.) Ultimately, these destructive reactions will kill cells through apoptosis or necrosis. This mechanism is identical to the mechanism of the disease Erythropoietic protoporphyria, which causes blistering in response to sun exposure due to a genetic defect in the same metabolic pathway. Advantages and limitations Unlike chemotheraphy for cancer the effect of PDT can be localised. Specificity of treatment is achieved in three ways. First, light is delivered only to tissues that a physician wishes to treat. In the absence of light, there is no activation of the photosensitizer and no cell killing. Second, photosensitizers may be administered in ways that restrict their mobility. In our example, ALA was only applied to the area to be treated. Finally, photosensitizers may be chosen which are selectively absorbed at a greater rate by targeted cells. ALA is taken up much more rapidly by metabolically active cells. Since malignant cells tend to be growing and dividing much more quickly than healthy cells, the ALA targets the unhealthy cells. PDT can be much cheaper than the alternative radiotherapy or surgical operation and after care. Post operative recovery is typically hours or days rather than weeks.A major limitation of PDT is that the light needed to activate most photosensitizers can not penetrate through more than one third of an inch (1 cm) of tissue using standard laser technology and low powered LED technolgy. Laser application of PDT is limited to the treatment of tumours on or under the skin, or on the lining of some internal organs. Moreover it is less effective in treatment of large tumours and metastasis for the same reason. However new high powered LED technogy has been lab tested to provide a depth of 2 inches from surface in a simulated breast tissue. Also hollow needles have been used by some units to get the light into deeper tissuesPhotosensitizers A wide array of photosensitizers for PDT exist. Some examples include aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, m-tetrahydroxyphenylchlorin (mTHPC), and mono-L-aspartyl chlorin e6 (NPe6). Several photosensitizers are also commercially available, such as Photofrin, Visudyne, and LS11.Although these photosensitizers can be used for wildly different treatments, they all aim to achieve certain characteristics: High absorption at long wavelengths Tissue is much more transparent at higher wavelengths (~700-850 nm). Absorbing at longer wavelengths would allow the light to penetrate deeper, and allow the treatment of larger tumors. High singlet oxygen quantum yield Low photobleaching Natural fluorescence Many optical dosimetry techniques, such as fluorescence spectroscopy, depend on the drug being naturally fluorescent High chemical stability Low dark toxicity The photosensitizer should not be harmful to the target tissue until the treatment beam is applied. Preferential uptake in target tissue The major difference between different types of photosensitizers is in the parts of the cell that they target. Unlike in radiation therapy, where damage is done by targeting cell DNA, most photosensitizers target other cell structures. For example, mTHPC has been shown to localize in the nuclear envelope and do its damage there. In contrast, ALA has been found to localize in the mitochondria and Methylene Blue in the lysosomes. The concept behind the comination of surgery and PDT for mesothelioma is that the surgery is used to treat the residual microscopic disease.It is naive to assume that there will not be at least microscopic disease remaining after even the most radical resection of a pleural mesothelioma that has presented in the usual diffuse manner.As a result ne can only achieve macroscopic debulking of the disease.This can be accompleshed by a lung-sparing pleurectomy or an xtrapleural pneumonectomy(EEP).Although it may be a challenging operation, EEP is the easiest way to achieve a complete deulking;however,it is likely to have signicant detrimental impact on the pacient's hemodynamic and pulmonary reserve. Source: http://books.google.com