The impact of complement activation on tumor oxygenation during photodynamic therapy.
The response to photodynamic therapy (PDT) mediated by photosensitizer Photofrin was examined with Lewis lung carcinomas growing in either complement-proficient C57BL/6 (B6) or complement-deficient complement C3 knockout (C3KO) mice. The results reveal that Photofrin-PDT was more effective in attaining cures of tumors in C3KO than in B6 hosts. Colony-forming ability of cells from tumors excised immediately after Photofrin-PDT confirmed that the direct cell killing effect was more pronounced in C3KO than in B6 hosts. In contrast, PDT mediated by photosensitizer benzoporphyrin derivative (BPD) produced higher cure rates of tumors in B6 hosts than those in C3KO hosts. Determination of tumor C3 levels by ELISA showed that Photofrin-PDT induced markedly more pronounced complement activation than BPD-PDT. Measurements of tumor oxygen tension immediately after PDT by Eppendorf pO2 histograph showed that Photofrin-PDT induced a marked decline in the oxygenation of tumors growing in B6 mice that was much less pronounced in C3KO hosts. With BPD-PDT the oxygen tensions in tumors in B6 and C3KO hosts decreased to a similar extent. This study indicates that complement activation in PDT-treated tumors that varies with different photosensitizers is an important determinant of tumor oxygen limitation effects directly associated with photodynamic action.
Cecic
Ivana
I
British Columbia Cancer Agency, Vancouver, BC, Canada.
Minchinton
Andrew I
AI
Korbelik
Mladen
M
D000818:Animals; D003167:Complement Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010778:Photochemotherapy
D010100:Oxygen