We investigated the efficacy of
photodynamic therapy (
PDT) using
talaporfin sodium as a new method of
synovectomy for
rheumatoid arthritis (RA). We first used RA synovial membrane (RASM) for in vitro and in vivo study. The RASM was obtained from patients with RA during
total knee replacement. In the in vitro study, RA fibroblast-like synoviocytes (RASCs) obtained from the RASM were examined by fluorescent microscopy to measure the intracellular localization of
talaporfin sodium. The cells were then subjected to
PDT, and their viability was examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium inner
salt assay. In the in vivo assay, RASM was obtained as described above, grafted onto
severe combined immunodeficiency (SCID) mice and subjected to
PDT. The damaged area of RASM was evaluated histologically at 1 day after
PDT. Next, we performed a separate experiment using rats with
collagen-induced arthritis (CIA). After
intra-articular injection of
talaporfin sodium, the concentration of
talaporfin sodium accumulated in the CIA synovial membrane (CIASM) was compared with that in cartilage, periarticular muscle, and skin. We then performed
PDT with
intra-articular injection of
talaporfin sodium and intra-articular irradiation. The damaged area of the CIASM was measured at 1 day after the
PDT, and the articular histological and radiological changes of the ankle were observed at 56 days after the
PDT. In RASM,
talaporfin sodium accumulated in lysosomes in vitro, and the
phototoxicity to RASCs in vitro and to RASM grafted onto SCID mice in vivo depended on the concentration of
talaporfin sodium and the
laser energy. In CIA rats, there was a greater accumulation of
talaporfin sodium in the CIASM than in normal tissue. The CIASM was selectively damaged at 1 day after the
PDT, and the bone and cartilage destruction were ameliorated at 56 days after the
PDT. In conclusion,
PDT using
talaporfin sodium might be a new method for
synovectomy in patients with RA.