Analysis of pulmonary microvasculature changes after photodynamic therapy delivered to distant sites

Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxic ity, by disruption of the microvasculature or by a combination of these eff ects. Although systemic effects after PDT of small tissue areas (<1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have describ ed animal death after high dose PDT to tumors on the hind limb of animals a nd hypothesized that a toxic shock syndrome caused by vasoactive agents rel eased after PDT is responsible. Because one of the most vulnerable organs t o toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber . The PDT treatment conditions (25 mg/kg Photofrin(R), 24 h, 150 J/cm(2) 63 0 nn, maximum area 6.28 cm(2)) were chosen that produce systemic toxicity a nd lethality in rats. Adhesion of leukocytes in the lung was monitored in v ivo using anti-CD-13-labeled microspheres, The progression of pulmonary ede ma was assessed by monitoring the leakage of rhodamine-labeled albumin and by wet-to-dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated . These data indicate that lung edema and acute respiratory distress syndro me is not the cause of death in these animals and that the toxicity is rela ted to other mechanisms including circulatory shock after extensive muscle damage.