MECHANISMS FOR OPTIMIZING PHOTODYNAMIC THERAPY - 2ND-GENERATION PHOTOSENSITIZERS IN COMBINATION WITH MITOMYCIN-C

Mechanisms for improving photodynamic therapy (PDT) were investigated in the murine RIF1 tumour using meso-tetrahydroxyphenylchlorin (m-THPC ) or bacteriochlorin a (BCA) as photosensitisers and comparing these r esults with Photofrin-mediated PDT. The Rb-86 extraction technique was used to measure changes in perfusion at various times after interstit ial PDT. Non-curative combinations of light doses with m-THPC and BCA PDT markedly decreased vascular perfusion. This decrease was more pron ounced for both new photosensitisers than for Photofrin. Comparison of tumour perfusion after PDT with tumour response revealed an inverse c orrelation for all three photosensitisers, but the relationship was le ss clear for m-TI-IPC and BCA. In vivo/in vitro experiments were perfo rmed after Photofrin or m-THPC PDT in order to assess direct tumour ki ll (immediate plating) vs indirect vascular effects (delayed plating). For both photosensitisers, there was little direct cell killing but c lonogenic survival decreased as the interval between treatment and exc ision increased. When m-THPC PDT was combined with mitomycin C (MMC), light doses could be decreased by a factor of 2 for equal tumour effec ts. Lower light and m-THPC doses could be used compared with Photofrin PDT in combination with MMC. BCA PDT with MMC did not result in a gre ater tumour response compared with BCA PDT alone. Reduction in both li ght and photosensitiser doses for effective PDT regimes in combination with MMC offers substantial clinical advantages, since both treatment time and skin photosensitisation will be reduced.