Photodynamic therapy

Under the photo or photodynamic therapy ( PDT) is defined as a method for treating tumors and other tissue changes such as vascular neoplasms with light in combination with a light-activated substance, called a photosensitizer, and oxygen present in the tissue. To this end, the patient is one that primarily non-toxic sensitizer or one of its metabolic precursors either systemically ( throughout the body distributing ) or locally administered, the due to certain characteristics of the tumor or tissue change (such as increased cell growth, increased metabolic activity or increased blood ) more or less selectively accumulates in the tumor or lesion. After a certain waiting time of the tumor or lesion will be irradiated with light of a suitable wavelength. Here are photophysical processes toxic substances, especially reactive oxygen species generated which damage the tumor or lesion.

Areas of application

The photodynamic therapy is particularly applicable if the microstructures of the tissue to be treated must be protected, as is the case in the gastrointestinal tract, brain or eye.

Ophthalmology

Photodynamic therapy is now used in ophthalmology as a standard procedure. She was long the only approved treatment method for certain types of vessel growth under the retina ( choroidal neovascularization ), as can occur for example in the wet form of age-related macular degeneration ( AMD). In Germany the benzoporphyrin derivative verteporfin for the treatment of AMD is approved, which can be activated with a special low-energy laser with a wavelength of 680 nm. The particular advantage of PDT in this application is the direct accessibility of the treatment site ( the retina) with the PDT laser through the patient's pupil. It can also be directly controlled by the same potential in the treatment mirroring the fundus the location and size of the irradiation field. With PDT, the newly formed vessels can be closed, thus avoiding further loss of vision. Simultaneously, the photoreceptors of the retina and the underlying pigment epithelium is protected by the relatively low laser power. In the meantime, are also medications available that are injected directly into the eye ( intravitreal ), such as Avastin, Lucentis, pegaptanib or triamcinolone and need not be activated by illumination for ophthalmological indications above. Some of these drugs are used in combination with PDT. In case of eye tumors such as childhood retinoblastoma first attempts to PDT with the then new porphyrins has been taken in the 1980s, which led, however, to be used because of the high doses to tissue damage in the eye. The PDT with photosensitizers such as verteporfin newer inserted here still in its infancy.

Oncology

Compared with surgical treatment provides photodynamic therapy has the advantage of a non- or minimally - invasive procedure. In particular, the required safety reasons spacious removal of healthy tissue in the tumor environment is eliminated. Irradiation requires about ten minutes to 100 minutes. Typical radiation levels are at 100 mW/cm2. Therefore, the heating of the tissue is only a few degrees Celsius. A general anesthetic is necessary only in the case of inaccessible internal organs. The PDT of tumors is normally done in a single treatment session, but there is a real possibility of repetition. Since the irradiation takes place with normal light, the burden of patients in comparison to the "classical" method of therapy is relatively low. Photodynamic treatment does not block the way for other therapies, that can be optionally carried out, should not be a complete cure was achieved.

The disadvantage of photodynamic therapy is essentially the low penetration depth of locally -applied photosensitizer (or its metabolic precursor ) of only a few millimeters and the limited penetration depth of light, so that usually only not advanced or flat -growing tumors are successfully treated. Therefore, mainly offer eg skin tumors such as actinic keratoses, the superficial (superficial ) basal cell carcinoma, as well as warts application for photodynamic therapy. Through the use of lasers in combination with optical fibers also tumors endoscopically accessible internal body surfaces to be treated. In addition, larger tumors can be treated by the insertion of such fibers in the fabric. However, this approach is rarely.

Photodynamic treatment of internal tumors is far less common and is usually used only palliative, such as in the esophagus, in bile duct and gallbladder cancer or brain tumors.

If the photosensitizer applied not only locally but also systemically, as is to be expected as a side effect with a significant temporary sensitivity to light, which can last in some cases for several weeks. The danger of the associated reduction in quality of life can be seen in palliative application of low life expectancy as an argument against therapy.

Although this process has been investigated at the beginning of the 20th century in Munich, it only gained in the 1980s by improving the photosensitizers and the use of lasers a certain distribution. Typical areas of tumors in the urinary bladder, in the outer head, in the oral cavity, larynx, esophagus, lung, bile duct and the genital area.

Dermatology

In dermatology, photodynamic therapy has been widely used to treat various skin cancers and their precursors. She is the first-line treatment for mild and moderate actinic keratosis. Two metabolic precursors of the photosensitizer protoporphyrin IX were authorized as medicinal products for the treatment of actinic keratoses, 5 -aminolevulinic acid ( 5 -ALA) and its methyl ester methyl -5-amino -4- oxopentanoate ( MAOP ). MAOP was also approved for the treatment of certain forms of basal cell carcinoma and Bowen's disease, for which the significantly newer drugs are not yet approved with 5- ALA. 5-aminolevulinic acid is in a skin penetration optimized nanoemulsion and in crystalline form as a medicinal plaster, MAOP as cream available. Promising studies and case reports suggest efficacy of photodynamic therapy for localized scleroderma, acne, psoriasis, various hyperkeratosis, virus-induced common warts and other chronic skin diseases.

Veterinary Medicine ( Veterinary Medicine )

Due to the surface effects of PDT ( up to 0.3 cm), this therapy is successful application such as squamous, but also for the virus-induced skin diseases and diseases of the sebaceous glands and hair follicles.

Biochemical bases

As photosensitizers mainly porphyrins are used, which can be activated by exposure to red light at a wavelength of 630 nm to 635 nm. Often 5-aminolevulinic acid or its methyl ester, methyl -5-amino -4- oxopentanoate ( MAOP ) is used, metabolic precursor of protoporphyrin IX, have been increased, that is relatively selective, are converted to tumor cells, or other tissue changes to the porphyrin. Newer sensitizers can be at even longer wavelengths stimulate with the advantage of a slightly larger penetration depth of light into the tissue.

Photosensitizers fluoresce in the rule and are therefore also used in the fluorescence diagnosis of tumors or other tissue changes. Photodynamic therapy ( PDT) is therefore closely related to the photodynamic diagnosis ( PDD, fluorescence diagnosis ( FD) ). Under certain circumstances, can be performed in the same session with the same first photosensitizer of photodynamic diagnosis and immediately photodynamic therapy.

The actual photophysical process involves several steps and requires the presence of oxygen which is present in sufficient quantity in most cells. A photosensitizer molecule absorbs a photon of light and is increased to the first excited singlet state. The greater the lifetime of this singlet state, the greater the likelihood for the rare transition into a likewise excited triplet state by intersystem crossing. Since optical transitions of this triplet state are very unlikely in the ground state, it has an unusually long life. This allows the contact with especially many molecules of interest. It impinges a molecule whose ground state is a triplet state, energy exchange is possible, and both molecules go into a singlet state. One of the few molecules with a triplet ground state molecular oxygen. Since the energy of the excited sensitizer molecule is greater than that required for a transition of the oxygen in an excited singlet state, the exchange of energy can take place. The resulting singlet oxygen in turn has a particularly large life in terms of an optical transition to the ground state. Due to its chemical reactivity, it can damage cellular components in the surrounding area by oxidation. This allows it to necrosis or - by acting on the mitochondrial membrane - a trigger apoptosis.

Light sources used

The spectrum of the light source must be matched to the photosensitizer used and contain one or more excitation bands ( absorption bands ) of the photosensitizer.

For photodynamic therapy are used:

Broadband emitters (for example, halogen spotlights)
Units with light emitting diodes ( LEDs)
Laser ( monochromatic coherent light, especially in the field of Ophthalmology)

In the broadband emitters of visible light can be filtered. By selecting appropriate color filter one or more excitation bands can for a particular photosensitizer, for example protoporphyrin IX ( endogenously from appliqued 5-aminolevulinic acid (delta -aminolevulinic acid, ALA ) was formed ), be specifically selected. (Example with the absorption spectrum of protoporphyrin IX, and the spectrum of a broadband radiator with the consequences of different filter in the visible range of the excitation of protoporphyrin IX in)