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

J Hepatobiliary Pancreat Sci. 2010 May;17(3):313-21. doi: 10.1007/s00534-009-0246-8. Epub 2010 Jan 19.

Abstract

Background: 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.

Methods: 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.

Results: The transmittance of the laser was 85-91% through yellow clear bile and that of the bile including 50 microg/ml NPe6 was 17-48%. The effective concentration of NPe6 which showed LD50 for a cell line was 12.5 microg/ml, and that of LD95 was 25 microg/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 +/- 44.6 mm(3) vs control 296.3 +/- 239.9 mm(3) P < 0.05). No severe hepatic disorder including Glisson components was observed by the histological findings.

Conclusion: 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.

MeSH terms

  • Biliary Tract Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Gallbladder Neoplasms / drug therapy
  • Hepatocytes / drug effects
  • Humans
  • Lethal Dose 50
  • Photochemotherapy / methods*
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / therapeutic use*

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Talaporfin