A.A.Radaev(1), V.A.Purtskhvanidze(1), E.Ph.Stranadko(2)

     (1)-The “Magic Ray” Moscow Center of Laser Medicine; Moscow, Russia
     (2)-State Research and Clinical Center for Laser Medicine of Russian Ministry of Health and Social
     Maintenance; Moscow, Russia

Photodynamic therapy (PDT) uses the local activation of a photosensitizer accumulated in a tumor by means of light. In the presence of tissue oxygen, this activation brings about a photochemical reaction that destroys tumor cells [1]. The PDT mechanism can be described as follows. When a photosensitizer molecule absorbs a quantum of light, it goes to an excited triplet state. The excited molecule can undergo photochemical reactions of two types. In the first type, the molecule reacts directly with biological molecules. This leads to the generation of free radicals. In the second type, an excited photosensitizer molecule reacts with an oxygen molecule. As a result, singlet oxygen is produced. This substance is a strong oxidant, which is cytotoxic in action.

PDT PARTICULARITIES AND ADVANTAGES:

1. Photosensitizers have a unique property to accumulate in tumors and other pathologic tissues in larger concentration than in the surrounding healthy tissues.
2. The main PDT damaging factors are active oxygen forms, and first of all, singlet oxygen; this substance is so reactive that it reacts practically at that site where it is generated not leaving the margins of pathologic (tumor) cells and thus, not damaging surrounding healthy tissues or not producing irreversible changes in these tissues.
3. Lasers and flexible monofiber quartz lightguides in combination with endoscopic equipment deliver the light for PDT precisely to any human organ or its part wherever it is located.
4. A constantly increasing number of photosensitisers with various useful parameters make PDT suitable for multiple applications both in oncology and in other fields of medicine.

PDT ADVANTAGES COMPARING TO TRADITIONAL TECHNIQUES USED FOR CANCER THERAPY:

• High effectiveness. Selectivity of the damage.
• A wide list of the indications (various locations, radical and palliative courses, preoperative PDT, combined treatment).
• A limited number of contraindications.
• Relative safety (no risk of surgical intervention, no heavy and systemic complications).
• Easy to perform.
• A single procedure. Multiple sessions are possible (if necessary).
• Combination of diagnostic and curative aspects.
• Well-tolerated by patients.
• PDT may be performed at the out-patient unit.
• Economic effectiveness.

Nowadays the most widespread photosensitizers are hematoporphyrin derivatives (Photofrin, Photohem). Photosensitizers of the first generation, however, have got a number of disadvantages: a low penetration of exciting light, which narrows the sphere of their usage; a long-lasting skin toxicity; low energy of light absorption.

For the last ten years there has been an intensive development of photosensitizers of the second generation with a short-time term of elimination and a bigger wavelength of exciting light, which provides a deep penetration into biological structures, as well as corresponds to other main requirements to a photosensitizers. Such photosensitizers are Russian-made chlorine derivatives Radachlorin and Photoditazine, as well as Belorussian compound Photolon, which have got corresponding permissions for clinical usage [2-4].

Photodynamic therapy, both in Russia and abroad, is applied in 65 to 70 percent of patients with skin cancer. In this case, PDT yields a 100% therapeutic efficiency [5].

Photodynamic therapy of skin cancer normally requires a single session under outpatient conditions, whereas a routine near-focus X-ray therapy lasts for 2 to 3 weeks. In this sense, PDT provides a much better economic efficiency with good healthy and cosmetic results.

We have got a big experience in using photosensitizers of the second generation from the group of derivatives for the performance of PDT in order to treat skin cancer under outpatient conditions.

The doses of Radachlorin and Photoditazine were 0.6 to 0.8 mg/kg, the drug-light interval was from 1 up to 4 hours, the dose of input light energy was 100 to 200 J/cm2.

The dose of Photolon was 1.2 to 1.5 mg/kg, the drug-light interval was 3 hours, the dose of input light energy was 150 to 200 J/cm2.

Efficacy of PDT with the chlorin e6 derivatives

The results of PDT with chlorine derivatives are estimated as good and perfect, due to the preservation of the collagenous structure of tissues and the healing of a tissue defect after resorption of a tumor by type of reparation, but not scarring.

CONCLUSION

Photosensitizers of the chlorine group have high photodynamic activity and therapeutic effectiveness. They quickly clear from the organism and due to this do not cause long-lasting photosensitization. It completely solves the problem of long-lasting skin phototoxicity which is the basic drawback of almost all photosensitizers which are applied in the clinic. Due to rapid accumulation in the tumor and due to high contrast gradient the photosensitizers of the chlorine raw allow to reduce the curative session from some days up to some hours.

PDT with application of chlorine derivatives under outpatient conditions is a comfortable and effective method for the treatment of skin cancer that provides good functional and cosmetic results.

References:

1. Henderson B.W., Dougherty T.J. How does photodynamic therapy work? // J. Photochem. Photobiol. – 1992. - Vol. 55. - P. 145-157.
2. Stranadko E.Ph., Ponomarev G.V., Meshkov V.M. et al. The first experience of Photodithazine clinical application for photodynamic therapy of malignant tumors. In Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IX, T.J.Dougherty, Editor // Proc. SPIE. – 2000. - Vol. 3909 (2000). – P. 138-144.
3. Reshetnikov A.V., Shvets V.I., Ponomarev G.V. In Advances of Porphyrin Chemistry, O.Golubchikov, Editor // St.Petersbourg: Research Institute for Chemistry of St.Petersbourg State University. - 1999. - Vol. 2. - Chapter 4. - P. 70-114.
4. Ivanov A.V., Reshetnikov A.V., Ponomarev G.V. One more PDT application of chlorine e6. In Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IX, T.J.Dougherty, Editor // Proc. SPIE. -2000. - Vol. 3909 (2000). P. 131-137.
5. Riabov M.V., Stranadko E.Ph., Volkova N.N. Photodynamic therapy of locally spread basal-cell skin cancer // J. Laser Medicine. – 2002. – Vol. 6, № 1. – P. 18-24.