Photodynamic therapy for cancers

Introduction:

This is an upcoming new modality of cancer treatment. It can be used in treating cancers of skin, larynx, nasopharyx, tumors of aerodigestive tract and endobronchial tumors. This is based on the principle of injecting a photosensitizing agent which is taken up preferentially by the tumor cells and exposing them to a specific wave length of laser. Laser activates the photosensitizing aggent which brings about destruction of cancer cells with sparing of normal tissues.

History of PDT:

The first clinical application of photodynamic therapy was described by von Tappeinerr and Jesionek in 1903. They used eosin topically to basal cell carcinomas prior to illumination. It was in 1975 Dougherty who reported that hematoporphyrin derivative in combination with red light could completely eradicate mouse mammary tumor growth.

This therapy has been used for recurrences following surgery, irradiation or chemotherapy. Photosensitive agents are used intravenously and include haematoporphyrin derivative for head and neck tumors and photosan-3 for endobronchial tumors. Topical sensitizer, delta aminolevulinic acid has been used for skin cancers like basal cell carcinoma and Bowen disease.

Commonly used laser in this type of therapy is argon tunable dye laser with wave lengths of 630 nm. This laser has also the advantage of being delivered via flexible fibers. Patients who are recieving photodynamic therapy should avvoid exposure to sunlight and should also use sun protective clothing to avoid photosensitive skin reactions.

Photodynamic therapy can also be used to manage dysplastic lesions, and early carcinoma of larynx. The main advantage of this procedure is its ability to preserve normal endolaryngeal tissue while effectively treating the lesion.

The efficacy of PDT in the treatment of cancer depends on the type of photosensitizer used, its intracellular localization, the dose of laser light used, and availability of oxygen. Singlet oxygen generated by the photochemical reaction can directly kill tumor cells by inducing apoptosis and necrosis. It also causes damage to nearby blood vessels thereby causing indirect killing of cells via hypoxia and starvation. PDT also stimulates immune response against remaining tumor cells. The outcome of PDT hence is dependent on all these mechanisms.

Singlet oxygen is highly reactive and can diffuse only 0.p1-0.02 micrometers during its very brief lifetime. The sensitizer hence should be localised close to its target tissue at the time of illumination.

Photosensitizers used:

Ideal photosensitizer should be a chemical that is pure and should be preferentially taken up by the tumor cells. It should be rapidly cleared from the system. It should have a strong absorption peak light wavelengths at more than 630 nm.

Porfimer sodium:

This is the first generation photosensitizer used. These first generation photosensitizors are hematoporhyrin and its derivatives. These agents preferentially gets localized in tumors and tends to produce tumoricidal effects when combined with red light.

Porfimer sodium is a mixture of various hematoporphyrin products with several absorption peaks. Light of 630 nm wavelength is used often to activate porfimer sodium, because light with a long wavelength can penetrate deeper in to the tissue. Therapeutic dose of porfimer sodium results in skin photosensitivity for 4-12 weeks.

ALA:

This is a second generation photosensitizer. ALA itself has no photosensitizing effect, but is a natural precursor of heme. It releases protoporphyrin which has photosensitizing properties. The light absorption spectrum is more or less simolar to that of Porfimer sodium.

There is rapid clearance of porfimer sodium limiting skin photosensitivity to 1-2 days. It can also be applied topically as a treatment of skin cancer. It can also be used to manage oral cancers, cancers involving the digestive tract. The major disadvantage of ALA is that it is strongly hydrophilic and hence will not be able to enter cells easily. Hence several alkyl esters of ALA that permeates into the cell easily have been developed. Methyl ester of ALA is commonly used one.

mTHPC:

This has been recently approved for use in the management of cancer. This sensitizer has been used as a palliative treatment of head and neck cancer. This is a more potent photosensitizer thatn porfimer sodium or ALA and hence requires administration of smaller doses. Its absorption peak is at 652 nm compared to that of 630 nm for both profirmer sodium and ALA, this slightly increases the depth of penetration of light.

Lights used:

1. Lasers can be used (it should be of precise activation wavelength)

2. Conventional broad spectrum sources like arc lamps can be used

Advantages of PDT:

1. The procedure is rather simple and does not need prolonged hospitalization

2. There is excellent chance of organ preservation

3. PDT can be repeated without additional permanent damage to normal tissues.