UPTAKE OF VERTEPORFIN(R) BY ARTICULAR TISSUES FOLLOWING SYSTEMIC AND INTRAARTICULAR ADMINISTRATION

Photodynamic therapy (PDT) using the photosensitizer BPD-Verteporfin ( Liposomal benzoporphyrin derivative-monoacid ring A) has been shown in previous studies to be effective in the amelioration of inflammatory arthritis in both the MRL-lpr mouse and the New Zealand White (NZW) ra bbit models, and could potentially offer alleviation of certain inflam mation-related symptoms of rheumatoid arthritis. Time and dose depende ncy of BPD-MA tissue uptake was carried out in the inflamed synovium a nd other articular and peri-articular tissues following intravenous an d intra-articular administration in the NZW rabbit model. As some arti cular and peri-articular tissues are difficult to extract, this study uses a rapid fluorimetric sampling of tissues following dissolution in Soluene 350. Our results showed that i.v. injected BPD-MA preferentia lly distributed in the inflamed synovium, and in tissues with a high d egree of vascularization. Little or no association was found with avas cular tissues such as cartilage and tendons. Clearance from the synovi um was rapid, supporting earlier rather than late light treatment. Muc h higher association of BPD-MA with the synovium was achieved using in tra-articular injection, and BPD-MPI concentrations were maintained at relatively steady levels for several hours. These observations suppor t the possibility that PDT could offer a safe, highly Versatile clinic al option for the management of inflamed joints in autoimmune disorder s. (C) 1998 John Wiley & Sons, Ltd.