PHOTODYNAMIC SYNOVECTOMY USING BENZOPORPHYRIN DERIVATIVE IN AN ANTIGEN-INDUCED ARTHRITIS MODEL FOR RHEUMATOID-ARTHRITIS

Experimental photodynamic therapy (PDT) has recently been adapted for the treatment of inflammatory and rheumatoid arthritis. The biodistrib ution of benzoporphyrin derivative monoacid ring A (BPD-MA) and the ef fect of percutaneous light activation via intra-articular bare cleaved optical fibers was investigated using a rabbit-antigen-induced arthri tis model. Qualitative evaluation of intra-articular photosensitizer c learance was performed with laser-induced fluorescence from 0 to 6 h f ollowing intravenous injection. The compound was rapidly taken up with in the joint and then cleared steadily over the 6 h interval. Biodistr ibution was determined by fluorescence microscopy and spectrofluorosco pic extraction techniques 3 h following intravenous injection of 2 mg/ kg BPD-MA. The biodistribution study demonstrated elevated levels of B PD-MA in synovium (0.35 mu g/g) and muscle (0.35 mu g/g). Fluorescence microscopy demonstrated presence of the compound within pathologic sy novium but absence of the photosensitizer within meniscus, ligament, b one and articular cartilage. Tissue effects were evaluated histologica lly at 2 and 4 weeks posttreatment. BPD-MA-mediated PDT caused synovia l necrosis in the region of light activation in 50% of treatment knees at 2 weeks and 43% at 4 weeks. No damage to nonpathologic tissues was observed. These studies indicate that selective destruction of synovi um can be achieved by the light-activated photosensitizing agent BPD-M A without damage to articular cartilage or periarticular soft tissues. PDT needs to be further evaluated to optimize treatment parameters to provide for a new minimally invasive synovectomy technique.