Inflammatory cells, most especially neutrophils, can be a necessary component of the anti-tumor activity occurring after administration of photodynamic therapy. Generation of neutrophil responses has been suggested to be particularly important in instances when the delivered PDT dose is insufficient. In these cases, the release of neutrophil granules and engagement of anti-tumor immunity may play an important role in eliminating residual disease. Herein, we utilize in vivo imaging of luminol chemiluminescence to non-invasively monitor neutrophil activation after PDT administration. Studies were performed in the AB12 murine model of mesothelioma, treated with Photofrin-PDT. Luminol-generated chemiluminescence increased transiently 1h after PDT, followed by a subsequent decrease at 4h after PDT. The production of luminol signal was not associated with the influx of Ly6G+ cells, but was related to oxidative burst, as an indicator of neutrophil function. Most importantly, greater levels of luminol chemiluminescence 1h after PDT was prognostic of a complete response at 90 days after PDT. Taken together, this research supports an important role for early activity by Ly6G+ cells in the generation of long-term PDT responses in mesothelioma, and it points to luminol chemiluminescence as a potentially useful approach for preclinical monitoring of neutrophil activation by PDT.

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