Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation photosensitizer

Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffuser tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.