의학강좌_전상훈

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1 Continuing Education Column Photodynamic Therapy Sanghoon Jheon, MD Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine J Korean Med Assoc 2007; 50(12): Abstract Clinical photodynamic therapy was introduced in the 1970s and has been shown to be an effective treatment modality in a variety of fields in oncology. Photodynamic therapy (PDT) is a local therapy such as radiation and surgery, which involves the photosensitization of neoplastic cells and tissues with porphyrins or related structures that catalyze, upon irradiation by laser, formation of reactive oxygen species. A photosensitizing agent is administered to the patient and after a period of h when the concentration of the photosensitizer is maximized in tumor tissue compared with normal tissue, and then the neoplastic mass is exposed to the laser light, which initiates the necrotic process. Despite the ability of PDT to destroy the tumor selectively, it has not been applied widely due to the lack of understanding of its therapeutic mechanism and clinical experiences as well as some limitations of currently available photosensitizers. Nowadays, the number of scientific articles on PDT, regarding clinical applications as well as basic science, made its application increasing. In one of the most suitable indications, lung cancer, PDT is a minimally invasive therapeutic option for the treatment of early cancer in airway and palliation for the endobronchial obstruction from central lung cancer. In esophageal cancer, PDT can also be applied to treat in early stage without muscle invasion or remnant cancer after endoscopic mucosal resection. Besides, PDT can be applied as a part of combined modality such as a neoadjuvant or adjuvant PDT. With the advances of new sensitizers and energy delivery system, clinical application of PDT will expand in near future. This review article will focus on the basic mechanism and the clinical investigations of PDT for the clinicians. Keywords : Photodynamic therapy; Photodynamic diagnosis; Laser; Photosensitizer; Cancer 1119

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3 Photodynamic Therapy Figure 1. Mechanism of the chemical tumor destruction. 1121

4 Jheon S S 1 t~10-6 s Type I Reaction (Free Radical Process) 4 7 O t~10-2 s T 1 1 O 2 O 2 - (Superoxide) Type II Reaction 3 O 2 S 0 1. Absorption; 2. Fluorescence; 3. Nonradiative Decay 4. Intersystem Crossing; 5. Phosphorescence 6. Energy Transfer; 7. Electron Transfer Figure 2. Photochemical reactions. 1122

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6 Jheon S Figure 3. Bronchoscopic finding of the distal tracheal cancer just above the carina one year after left upper sleeve lobectomy (left). Bronchoscopic finding shows disappearance of the tumor with normal mucosa 6 months after PDT (right). 1124

7 Photodynamic Therapy Figure 4. Double primary lung cancer at right upper lobe and lower lobe. Bronchoscopic finding shows a protruding mass at right lower lobe basal segment before photodynamic therapy(left). Bronchoscopic finding shows disappearance of mass 1 year after photodynamic therapy (Right). 1125

8 Jheon S Figure 5. Photodynamic therapy for esophageal cancer. A) esophageal cancer, T1N0M0. B) one month after PDT, exudative peel on the tumor. C) five months after PDT, normal esophageal mucosa. A B C 1126

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10 Jheon S 11. Finsen NR. Phototherapy. London: Edward Arnold, Daniell MD, Hill JS. A history of photodynamic therapy. Aust NZ J Surg 1991; 61: Ackroyd R, Kelty C, Brown N, Reed M. The history of photodetection and photodynamic therapy. Photochem Photobiol 2001; 74: Dougherty T, Kaufman J, Goldfarb A, Weishaupt K, Boyle D. Photodynamic therapy for the treatment of malignant tumors. Cancer Resear 1978; 38: Hayata Y, Kato H, Konaka C, Ono J, Takizawa N. Hematoporphyrin derivative andlaser photoradiation in the treatment of lung cancer Chest 1982; 81: Schaffer M, Sroka R, Fuchs C, Schrader Reichardt U, Schaffer PM, Busch M, Dühmke E. Biomodulative effects induced by 805 nm laser light irradiation of normal and tumor cells. J Phtochem Photobiol 1997; 40: Maegawa Y, Itoh T, Hosokawa T, Yaegashi K, Nishi M. Effects of near infrared low level laser irradiation on microcirculation. Lasers Surg Med 2000; 27: Dennis ED, Fukumura D, Rakesh KJ. Photodynamic therapy for cancer. Nature Review 2003; 3: Dougherty TJ. An Update on photodynamic therapy application. J Clinical Laser Med & Surg 2002; 20: Peng Q, Moan J, Nesland JM. Correlation of subcellular and intratumoral photosensitizer localization with ultrastructural features after photodynamic therapy. Ultrastuct Pathol 1996; 20: Fingar VH, Taber SW, Haydon PS, Harrison LT, Kempf SJ, Wieman TJ. Vascular damage after photodynamic therapy of solid tumors: a view and comparison of effect in pre clinical and clinical models at the University of Louisville. In Vivo 2000; 14: Xue L, He J Olenick NL.Promotion of photodynamic therapy induced apoptosis by stress kinases. Cell Death Differ 1999; 6: Moan J. properties for optimal PDT sensitizers. J Photochem Photobiol B 1990; 5: Gold MH. Aminolevulinic acid photodynamic therapy: Medical evidence for its expanded use. Expert Rev Med Devices 2006; 3: Kim BM, Lim HS. Biomedical Optics and Laser treatment Optical Science and Technology 2003; 7: Stringer MR, Kelty CJ, Ackroyd R, Brown SB. Light dosimetry measurements during ALA PDT of Barrett s esophagus. Photodiagnosis and Photodynamic Therapy 2006; 3: Maziak DE, Markman BR, MacKay JA. Evans WK. Photodynamic therapy in non small cell lung cancer: A systematic. Ann Thorac Surg 2004; 77: McBride G, Studies expand potential uses of photodynamic therapy. J Natl Cancer Inst 2002; 94: Wiedmann MW, Caca K. General principles of photodynamic therapy (PDT) and gastrointestinal applications. Curr Pharm Biotechnol 2004; 5: Yoon SH, Han KT, Kim KN, Lee SI. Effect of photodynamic therapy in lung cancer. Tuberc Respir Dis 2004; 57: Jheon. Photodynamic Therapy. Seoul: Korea Medical Book Publisher Co., 2007:

11 Photodynamic Therapy Peer Reviewer Commentary 1129

A 617

A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R