Novel photodynamic therapy against biliary tract carcinoma using mono-l-aspartyl chlorine e6: basic evaluation for its feasibility and efficacy

Recently, a second-generation photosensory agent for photodynamic therapy (PDT), mono-l-aspartyl chlorine e6 (NPe6), which degrades rapidly in vivo, has been developed. We evaluated its feasibility and efficacy for treatment in biliary tract carcinoma. A transmittance of semiconductor laser light (664 nm), sensitivity of a human biliary tract carcinoma cell line, and disorder to normal tissue including Glissonian constructs and adjacent hepatocytes were investigated. The transmittance of the laser was 85-91% through yellow clear bile and that of the bile including 50 mu g/ml NPe6 was 17-48%. The effective concentration of NPe6 which showed LD50 for a cell line was 12.5 mu g/ml, and that of LD95 was 25 mu g/ml. NPe6 in the supernatant reduced laser transmissiveness, but it had little influence on the antitumor effect in supernatant with or without NPe6. The NOZ cell-tumor volume was reduced significantly 14 days after irradiation in the PDT group (PDT 69.9 +/- A 44.6 mm(3) vs control 296.3 +/- A 239.9 mm(3) P < 0.05). No severe hepatic disorder including Glisson components was observed by the histological findings. NPe6 PDT was effective in carcinomas even in the presence of bile, and causes no serious complication for the liver and Glisson structure. Therefore, NPe6 PDT will be a useful candidate as a new therapy for biliary tract carcinomas.