Fluorescence Diagnosis and Photodynamic Therapy in Dermatology

Summary In several countries throughout the world the photosensitiser Photofrin® has been approved for systemic photodynamic therapy (PDT) for different oncological indications. However, owing to the prolonged cutaneous photosensitization entailed, the use of this porphyrin derivative is restricted. Currently, the most promising sensitizers in dermatology that can be applied topically are 5-aminolevulinic acid (ALA) or ester derivatives that are precursors of heme biosynthesis. ALA has shown good clinical and excellent cosmetic results in superficial skin cancer and precancerous conditions, e.g. superficial basal cell carcinoma (BCC), or actinic keratoses (AK). ALA-PDT for AK was approved by the FDA in late 1999 and the corresponding registration process for ALA-methyl ester in Europe led to approval in 2001. Besides its usefulness in PDT, ALA also has a unique feature that can be exploited for diagnostic purposes: after topical or systemic application protoporphyrin IX is induced rather selectively in epithelial tumours, with a high tumour-to-surrounding tissue ratio. Upon irradiation with light the tumour becomes visible and can be delineated from the surrounding tissue. This procedure called fluorescence diagnosis (FD) will enable the dermatologist to perform either a directed biopsy or very likely a controlled and complete resection of the tumour sparing vital tissue. By using a CCD camera system together with digital imaging, the contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold, which can be utilized either for a directed biopsy or for preoperative planning when Moh's surgical technique is scheduled. Moreover, FD is a helpful tool to prove the efficacy of PDT. At present, the routine employment of such systems is being assessed in prospective studies.

[1]  H Stepp,et al.  Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. , 1998, Neurosurgery.

[2]  R. Anderson,et al.  The optics of human skin. , 1981, The Journal of investigative dermatology.

[3]  Johan Emelian Moan,et al.  Choice of the proper wavelength for photochemotherapy , 1996, European Conference on Biomedical Optics.

[4]  B Palcic,et al.  Detection of dysplasia and carcinoma in situ by ratio fluorometry. , 1992, The American review of respiratory disease.

[5]  A. Goetz,et al.  Active and higher intracellular uptake of 5-aminolevulinic acid in tumors may be inhibited by glycine. , 1999, The Journal of investigative dermatology.

[6]  D. W. Rogers,et al.  Methods for the endoscopic photographic and visual detection of helium cadmium laser‐Induced fluorescence of photofrin II , 1990, Lasers in surgery and medicine.

[7]  Martin Kriegmair,et al.  5-Aminolevulinic Acid-Induced Fluorescence Endoscopy for the Detection of Lower Urinary Tract Tumors , 1999, Urologia Internationalis.

[8]  C. Whitehurst,et al.  Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma. , 2001, Archives of dermatology.

[9]  N. Bendsoe,et al.  Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial , 2001, The British journal of dermatology.

[10]  H Kerl,et al.  Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas? , 1993, Journal of the American Academy of Dermatology.

[11]  M Landthaler,et al.  PENETRATION POTENCY OF TOPICAL APPLIED δ‐AMINOLEVULINIC ACID FOR PHOTODYNAMIC THERAPY OF BASAL CELL CARCINOMA * , 1994, Photochemistry and photobiology.

[12]  M. Landthaler,et al.  Long‐pulse dye laser for photodynamic therapy: Investigations in vitro and in vivo , 1999, Lasers in surgery and medicine.

[13]  H Stepp,et al.  Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. , 1996, The Journal of urology.

[14]  J Moan,et al.  Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues. , 1997, Cancer Letters.

[15]  M. Landthaler,et al.  Topical 5-aminolevulinic acid for photodynamic therapy of basal cell carcinoma. Evaluation of stratum corneum permeability in vitro , 1996 .

[16]  G. Jori,et al.  Tumour photosensitizers: approaches to enhance the selectivity and efficiency of photodynamic therapy. , 1996, Journal of photochemistry and photobiology. B, Biology.

[17]  M. Landthaler,et al.  Non-oncologic indications for ALA-PDT , 2002, The Journal of dermatological treatment.

[18]  R. M. Szeimiesa,et al.  Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. , 2002 .

[19]  Pratt Jh,et al.  HEMATOPORPHYRINE DERIVATIVE FOR DETECTION OF CERVICAL CANCER. , 1964 .

[20]  H Messmann,et al.  Endoscopic fluorescence detection of dysplasia in patients with Barrett's esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization. , 1999, Gastrointestinal endoscopy.

[21]  H. Lui Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: an update. , 1994, Seminars in oncology.

[22]  T. Ruzicka,et al.  Successful Surgery of Multiple Recurrent Basal Cell Carcinomas Guided by Photodynamic Diagnosis , 1997, Aesthetic Plastic Surgery.

[23]  J. Nelson,et al.  Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study. , 1997, Archives of dermatology.

[24]  J C Kennedy,et al.  Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. , 1992, Journal of photochemistry and photobiology. B, Biology.

[25]  M Landthaler,et al.  Simulations on the selectivity of 5-aminolaevulinic acid-induced fluorescence in vivo. , 1998, Journal of photochemistry and photobiology. B, Biology.

[26]  F. Figge,et al.  Cancer Detection and Therapy. Affinity of Neoplastic, Embryonic, and Traumatized Tissues for Porphyrins and Metalloporphyrins.∗ , 1948, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[27]  M. Landthaler,et al.  Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study. , 1996, Dermatology.

[28]  H Stepp,et al.  Inhalation of 5-aminolevulinic acid: a new technique for fluorescence detection of early stage lung cancer. , 1996, Journal of photochemistry and photobiology. B, Biology.

[29]  Rolf-Markus Szeimies,et al.  Topical photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic keratoses: a first clinical study , 1996, European Conference on Biomedical Optics.

[30]  J. Krutmann Dermatological phototherapy and photodiagnostic methods , 2001 .

[31]  C. Whitehurst,et al.  Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease , 1996, The British journal of dermatology.

[32]  J. Moan PORPHYRIN PHOTOSENSITIZATION AND PHOTOTHERAPY , 1986, Photochemistry and photobiology.

[33]  B. Ortel,et al.  Photodynamic therapy and fluorescence diagnosis in dermatology , 2001 .