Photodynamic therapy for Oral diseases

Transcription

1 Review Article Photodynamic therapy for Oral diseases Komali G 1, Rani J 2, B Praveen Kumar 3, S Sudhakar 4 1 Associate professor, 2 Professor & Head, 3,4 Senior lecturer, Department of Oral Medicine and Radiology, St. Joseph Dental College, Eluru, India. Abstract Photodynamic therapy (PDT) is a treatment modality that has been developing rapidly within various medical specialties since the 1980s. Photodynamic therapy involves three key components: a photosensitizer, light and tissue oxygen. Photoreactive chemicals are injected into the patient and irradiated with light strong enough to activate the chemicals, causing them to emit free radicals and destroy the targeted abnormal cells. Photodynamic therapy represents another potential and effective modality for the treatment of certain malignances, infectious diseases, and various skin conditions including basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs), actinic keratoses, Bowen s disease, psoriasis, cutaneous T-cell lymphoma, acne and photorejuvenation of wrinkles. Key words: Photodynamic therapy, photosensitizer, dye, cancer, oxygen. Corresponding Author: G. Komali, Associate professor, Department of Oral Medicine & Radiology, St. Joseph Dental College, Eluru, AP, India. komali_garlapati@yahoo.co.in Received: 11 September 2009 Accepted: 8 November Introduction Photodynamic therapy (PDT), also known as photo radiation therapy, phototherapy, or photo chemotherapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Allison et al. (2006) have described PDT as the therapy that is truly the marriage of a drug and a light.(1) The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Photodynamic reaction Photodynamic therapy involves three components like Light, photosensitizer and oxygen. A photosensitizer or its metabolic precursor is administered to the patient. Upon irradiation with light of a specific wavelength, the photosensitizer undergoes a transition from a low-energy ground state to an excited singlet state (Fig 1). Subsequently, the photosensitizer may decay back to its ground state, with emission of fluorescence, or may undergo a transition to a higher-energy triplet state. The triplet state can react with endogenous oxygen to produce singlet oxygen and Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1

2 other radical species, causing a rapid and selective destruction of the target tissue (Fig 2). Light Sources PDT requires a source of light that activates the photosensitizer by exposure to low-power visible light at a specific wavelength. Human tissue transmits red light efficiently, and the longer activation wavelength of the photosensitizer results in deeper light penetration. Consequently, most photo sensitizers are activated by red light between 630 and 700 nm, corresponding to a light penetration depth from 0.5 cm (at 630 nm) to 1.5 cm (at 700 nm), this limits the depth of necrosis or apoptosis and defines the therapeutic effect. In the past, Argon-pumped dye lasers, Potassium titanyl phosphate (KTP) or Neodymium: Yttrium aluminum garnet (Nd/YAG)-pumped dye lasers and gold vapor- or copper vapor-pumped dye lasers were used as light sources. All these laser systems were complex and expensive. At present, diode laser systems are used predominantly, that are easy to handle, portable and cost-effective. For treatment of larger areas, non-coherent light sources, such as tungsten filament, quartz halogen, xenon arc, metal halide and phosphorcoated sodium lamps are in use. Recently non-laser light sources, Such as light-emitting diodes (LED) have also been applied in PDT.(1) These light sources are much less expensive and are small, lightweight, and highly flexible (Fig 3). Sources used for light delivery in PDT may vary depending upon the location and morphology of the lesion, but are typically fiber-optic catheters terminated with cylindrical diffusers or lenses for flat-field applications. Photosensitizers can be illuminated by different techniques, which include superficial, interstitial, intra-operative and intra-cavitary methods. Interstitial light delivery is appropriate for tumors in which surgery would involve extensive resection, or for those that are not suitable for surgery. Intra-operative technique is used as an adjuvant treatment in anatomically complex areas, in which the photosensitizer is applied to the patient several days prior to the operation, and resection of the tumor is followed by photosensitizer activation. The requirements of an optimal photosensitizer (Fig 4) include: 1. Highly selective tumor accumulation 2. Low toxicity and fast elimination from the skin and epithelium 3. Absorption peaks in the low-loss transmission window of biological tissues 4. Optimum ratio of the fluorescence quantum yield to the interconversion quantum yield The first parameter determines the photosensitizer diagnostic capabilities and plays a key role in monitoring the photosensitizer accumulation in tissues and its elimination from them. The second parameter determines the photosensitizer ability to generate singlet oxygen. Photofrin (dihematoporphyrin ether) and hematoporphyrin derivatives (HPDs) are referred to as first-generation sensitizers. Photofrin is the most extensively studied and clinically used photosensitizer. Second-generation photo sensitizers include 5- aminolevulinic acid (ALA), benzoporphyrin derivative (BPD), Foscan (mthpc). Foscan (mthpc) is the most potent second-generation photosensitizer that has been reported to be 100 times more active than Photofrin in animal studies. ALA is an intrinsic photosensitizer that is converted in situ to a photosensitizer, protoporphyrin IX. Topical ALA and its esters have been used to treat pre-cancer conditions and carcinomas of the skin. Third-generation photo sensitizers include currently available drugs, that are modified by Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1 51

3 targeting with monoclonal antibodies or with non antibody based protein carriers and protein receptor systems, and conjugation with a radioactive tag. Fig 3: Non-laser light sources PDT in dentistry is growing rapidly and can be used in many ways. The photodynamic diagnosis (PDD) of the lesions with malignant transformation can be done in the early stages. PDT has shown potential in treatment of oral leukoplakia, oral lichen planus, and head and neck cancers. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic and viral infections (Fig 5). Fig 1: Activation of photosensitizer Fig 4: Photosensitizers Fig 2: Photodynamic Reaction Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1 52

4 Anticancer therapy Photodynamic therapy is having many potential advantages over conventional anti cancer therapies.(2) PDT is noninvasive, can be performed in outpatient or day-care (inpatient) settings. Early or localized diseases can be targeted accurately and selectively. In PDT illumination of the whole body is not necessary, improving the quality of life and survival rate. In PDT repeated doses can be given without the need for totaldose limitations. PDT shows excellent cosmetic results and the healing process results in little or no scarring. It can offer organ-sparing treatment worldwide, with very little investment in infrastructure and moderate side effects.(3) Photodynamic antimicrobial chemotherapy of dental and mucosal infections [PACT]: It has been known since the beginning of the last century that micro-organisms can be killed by the combination of dyes and light, but the interest in antimicrobial PDT was hampered by the introduction of antibiotics. In recent years, the emergence of antibiotic resistant strains, such as methicillin resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, stimulated a search for alternative treatments. PACT has the potential to be such an alternative, especially for the treatment of localized infections of the skin and the oral cavity. Micro-organisms that are killed by PACT include bacteria, fungi, viruses and protozoa. The development of resistance to PACT appears to be unlikely, since in microbial cells, singlet oxygen and free radicals interact with several cell structures and different metabolic pathways. PACT is equally effective against antibioticresistant and antibiotic-susceptible bacteria and repeated photosensitization has not induced the development of resistant strains. The oral cavity is colonized by complex, relatively specific and highly interrelated micro-organisms, including aerobic, anaerobic Gram-positive and Gramnegative bacteria, fungi, mycoplasma, protozoa and viruses. The antimicrobial activity of photosensitizers is mediated by singlet oxygen, which because of its high chemical reactivity, has a direct effect on extra cellular molecules. Thus the polysaccharides present in bacterial biofilms are also susceptible to photo damage; such dual activity is not exhibited by antibiotics. PACT reduced bacterial counts of Prevotella sp., Fusobacterium sp., Streptococcus betahaemolyticus, biofilms of Streptococcus intermedius, Proteus mirabilis, Pseudomonas aeruginosa, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Candida albicans and related Candida sp.(4) Major side-effect after the use of intravenous photosensitizer is photosensitivity. Systemic administration of the sensitizer results in a period of residual skin photosensitivity due to accumulation of the photosensitizer in the skin. Bright light or direct sunlight must be carefully avoided to prevent sunburn, redness and swelling, for a period ranging from several hours or weeks until the drug is eliminated from the body. Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1 53

5 Recent clinical advances in PDT: Rapid cytotoxic and vasculotoxic reactions result in visible tumor destruction and sparing of normal tissue, which makes PDT appealing to both patients and clinicians. While PDT is currently applied mostly in oncological therapy, in the future it will be most likely applied to other areas.(5,6) Clinical PDT is continuing to grow because of the relatively recent availability of portable and dependable light sources. PDT could offer organ sparing treatment worldwide with very little investment in infrastructure and could be highly successful under relatively primitive conditions. A new device based on LED technology (Light Sciences Corporation, Issaquah, WA, USA) allows for the production of light inside the target tissue. This new technology could expand the use of PDT for the treatment of moderate and largevolume refractory tumors.(7) Current controversies in PDT: (i) Clinicians resistance to a new approach, (ii) The cost of setting up a PDT center, (iii) The previous lack of inexpensive and convenient light sources. Moreover, to establish clear advantages over alternative treatments, the existing photo sensitizers and light sources have to be evaluated in large controlled, comparative, randomized clinical trials. Fig 5: PDT and PACT Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1 54

6 Conclusion The future of PDT will depend on the interactions between clinical applications and technological innovations and only interdisciplinary research approaches can overcome all the difficulties and challenges of PDT. References 1. Allison RR, Downie GH, Cuenca R, Hu XH, Childs C, Sibata CH (2004a). Photosensitizers in clinical PDT. Photodiagn Photodyn Ther 1: Biel MA (1996b). Photodynamic therapy as an adjuvant intraoperative treatment of recurrent head and neck carcinomas. Arch Otolaryngol Head Neck Surg 122: Biel MA (1996a). Photodynamic therapy and the treatment of head and neck cancers. J Clin Laser Radiat Surg 14: Bhatti M, MacRobert A, Meghji S, Henderson B, Wilson M (1998). A study of the uptake of toluidine blue O by Porphyromonas gingivalis and the mechanism of lethal photosensitization. Photochem Photobiol 68: Biel MA (2002). Photodynamic therapy in head and neck cancer. Curr Oncol Rep 4: Biel M (2006). Advances in photodynamic therapy for the treatment of head and neck cancers. Lasers Surg Med 38: Brown SB, Brown EA, Walker I (2004). The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol 5: Journal of Dental Research and Rehabilitation / December 2009 / Vol. 1 / Issue 1 55