ENHANCEMENT OF 5-AMINOLEVULINIC ACID-INDUCED PHOTODYNAMIC THERAPY IN NORMAL RAT COLON USING HYDROXYPYRIDINONE IRON-CHELATING AGENTS

Currently, the clinical use of 5-aminolaevulinic acid (ALA)-induced pr otoporphyrin IX (PPIX) for photodynamic therapy (PBT) is limited by th e maximum tolerated oral ALA dose (60 mg kg(-1)). This study investiga tes whether hydroxypyridinone iron-chelating agents can be used to enh ance the tissue levels of PPIX, without increasing the administered do se of ALA. Quantitative charge-coupled device (CCD) fluorescence micro scopy was employed to study PPIX fluorescence pharmacokinetics in the colon of normal Wistar rats. The iron chelator, CP94, when administere d with ALA was found to produce double the PPIX fluorescence in the co lonic mucose, compared with the same dose of ALA given alone and to be more effective than the other iron chelator studied, CP20. Microspect rofluorimetric studies demonstrated that PPIX was the predominant porp hyrin species present. PDT studies conducted on the colonic mucosa sho wed that the simultaneous administration of 100 mg kg(-1) CP94 i.v. an d 50 mg kg(-1) ALA i.v, produced an area of necrosis three times large r than similar parameters without the iron-chelating agent with the sa me light dose. It is possible, therefore, to increase the amount of ne crosis produced by ALA-induced PDT substantially, without increasing t he administered dose of ALA, through the simultaneous administration o f the iron-chelating agent, CP94.