Photodynamic therapy

Description:
Photodynamic therapy (PDT), sometimes called photochemotherapy, is a form of phototherapy using nontoxic light-sensitive compounds that are exposed selectively to light, whereupon they become toxic to targeted malignant and other diseased cells (phototoxicity). PDT has proven ability to kill microbial cells, including bacteria, fungi and viruses. PDT is popularly used in treating acne. It is used clinically to treat a wide range of medical conditions, including wet age-related macular degeneration and malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic.

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Most modern PDT applications involve three key components: a photosensitizer, a light source and tissue oxygen. The combination of these three components leads to the chemical destruction of any tissues which have either selectively taken up the photosensitizer or have been locally exposed to light. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce reactive oxygen species. These reactive oxygen species generated through PDT are free radicals (Type I PDT) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II PDT). In understanding the mechanism of PDT it is important to distinguish it from other light-based and laser therapies such as laser wound healing and rejuvenation, or intense pulsed light hair removal, which do not require a photosensitizer.

Why it is done:
Photodynamic therapy (PDT) was first used in 1905 for the treatment of skin cancers. Since then, it has been further developed and used for the treatment of many kinds of cancers (lung, colon, etc.) as well as certain kinds of blindness. PDT combines a drug (called a photosensitizer) that is preferentially absorbed by certain kinds of cells and a special light source. When used together, the photosensitizer and the light destroy the targeted cells. More recently, however, PDT has been used for photorejuvenation, wrinkles, discoloration, visible veins, and acne. When used for these conditions, the photosensitizer is applied to the face and then the skin is exposed to a light source. Rapidly growing cells, oil glands, and other structures in the skin absorb the photosensitizer and are destroyed by a reaction caused by the light. Cosmetic improvement in wrinkling, age spots, and visible veins has been documented after PDT treatment.

It is a new advance in facial rejuvenation and there are currently different methods in use. For example some physicians use blue light, red light, or intense pulse light. The photosensitizer is applied to the skin and is left on for a variable period of time. The skin is then exposed to the light source and the photosensitizer is then removed. Reported side effects include transient burning, stinging, swelling, and redness. Side effects are variable depending on what is being treated, how long the photosensitizer is left on, and which light source is used. No long-term studies have been performed to evaluate long term side effects.
Procedure:
In order to achieve the selective destruction of the target area using PDT while leaving normal tissues untouched, either the photosensitizer can be applied locally to the target area, or photosensitive targets can be locally excited with light. For instance, in the treatment of skin conditions, including acne, psoriasis, and also skin cancers, the photosensitizer can be applied topically and locally excited by a light source. In the local treatment of internal tissues and cancers, after photosensitizers have been administered intravenously, light can be delivered to the target area using endoscopes and fiber optic catheters....CLICK & SEE

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Photosensitizers can also target many viral and microbial species, including HIV and MRSA. Using PDT, pathogens present in samples of blood and bone marrow can be decontaminated before the samples are used further for transfusions or transplants. PDT can also eradicate a wide variety of pathogens of the skin and of the oral cavities. Given the seriousness that drug resistant pathogens have now become, there is increasing research into PDT as a new antimicrobial therapy.

Photosensitizers:
In air and tissue, molecular oxygen occurs in a triplet state, whereas almost all other molecules are in a singlet state. Reactions between these are forbidden by quantum mechanics, thus oxygen is relatively non-reactive at physiological conditions. A photosensitizer is a chemical compound that can be promoted to an excited state upon absorption light and undergo intersystem crossing with oxygen to produce singlet oxygen. This species rapidly attacks any organic compounds it encounters, thus being highly cytotoxic. It is rapidly eliminated: in cells, the average lifetime is 3 µs.[5]

A wide array of photosensitizers for PDT exist. They can be divided into porphyrins, chlorophylls and dyes. Some examples include aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, m-tetrahydroxyphenylchlorin (mTHPC), and mono-L-aspartyl chlorin e6 (NPe6).

Several photosensitizers are commercially available for clinical use, such as Allumera, Photofrin, Visudyne, Levulan, Foscan, Metvix, Hexvix, Cysview, and Laserphyrin, with others in development, e.g. Antrin, Photochlor, Photosens, Photrex, Lumacan, Cevira, Visonac, BF-200 ALA. Amphinex. Also Azadipyrromethenes.

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 longer wavelengths (~700–850 nm). Absorbing at longer wavelengths would allow the light to penetrate deeper,[8] and allow the treatment of larger tumors.

*High singlet oxygen quantum yield

*Low photobleaching to prevent degradation of the photosensitizer

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*Natural fluorescence

*Many optical dosimetry techniques, such as fluorescence spectroscopy, depend on the drug being naturally fluorescent[10]

*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.

To allow treatment of deeper tumours some researchers are using internal chemiluminescence to activate the photosensitiser.

PUVA therapy is using psoralen as photosensitiser and UVA ultraviolet as light source, but this form of therapy is usually classified as a separate form of therapy from photodynamic therapy.

Targeted PDT:
Some photosensitisers naturally accumulate in the endothelial cells of vascular tissue allowing ‘vascular targeted’ PDT, but there is also research to target the photosensitiser to the tumour (usually by linking it to antibodies or antibody fragments). It is currently only in pre-clinical studies.

Applications:
Compared to normal tissues, most types of cancers are especially active in both the uptake and accumulation of photosensitizers agents, which makes cancers especially vulnerable to PDT. Since photosensitizers can also have a high affinity for vascular endothelial cells.

Usage in acne:
PDT is currently in clinical trials to be used as a treatment for severe acne. Initial results have shown for it to be effective as a treatment only for severe acne, though some question whether it is better than existing acne treatments. The treatment causes severe redness and moderate to severe pain and burning sensation. A phase II trial, while it showed improvement occurred, failed to show improved response compared to the blue/violet light alone
Advantages:
There are several advantages of photodynamic therapy over other forms of facial rejuvenation. For example, PDT is less destructive (and therefore less painful) than many of the deeper peels and lasers. There is also minimal recovery time. It is also a proven technique for the treatment of precancerous lesions. Thus, depending on the technique used, there may be an additional benefit of preventing skin cancer.

Disadvantages:
The disadvantage of photodynamic therapy is that it is new. Long-term side effects are unknown, and the benefits are not as well studied. For example, PDT is not known how long the benefits last.

Although PDT is a promising new therapy, you need to discuss the risks, benefits, and alternatives with your physician to decide if PDT is right for you.
Modern development of PDT in Russia:
Of all the nations beginning to use PDT in the late 20th century, the Russians were the quickest to advance its use clinically and to make many developments. One early Russian development was a new photosensitizer called Photogem which, like HpD, was derived from haematoporphyrin in 1990 by Professor Andrey F. Mironov and coworkers in Moscow. Photogem was approved by the Ministry of Health of Russia and tested clinically from February 1992 to 1996. A pronounced therapeutic effect was observed in 91 percent of the 1500 patients that underwent PDT using Photogem, with 62 percent having a total tumor resolution. Of the remaining patients, a further 29 percent had a partial tumor resolution, where the tumour at least halved in size. In those patients that had been diagnosed early, 92 percent of the patients showed complete resolution of the tumour.

Around this time, Russian scientists also collaborated with NASA medical scientists who were looking at the use of LEDs as more suitable light sources, compared to lasers, for PDT applications.

Modern development of PDT in Asia:
PDT has also seen considerably development in Asia. Since 1990, the Chinese have been developing specialist clinical expertise with PDT using their own domestically produced photosensitizers, derived from Haematoporphyrin, and light sources. PDT in China is especially notable for the technical skill of specialists in effecting resolution of difficult to reach tumours
Resources:
http://en.wikipedia.org/wiki/Photodynamic_therapy
http://www.dermanetwork.org/information/pdt.asp

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