Abstract
Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor®)-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.
Highlights
When combined with surgery, photodynamic therapy (PDT) of tumors can provide a means to eradicate residual disease that is unresectable for reasons that may include a lack of detectability, broad area of superficial involvement, or localization adjacent to vital structure
Low fluence rate is expected to be beneficial for intracavitory PDT as it is for other illumination geometries
This suggests that the daughters of PDT-treated cells may downregulate epidermal growth factor receptor (EGFR) expression. In contrast to these results, an in vivo study on the molecular effects of sub-lethal PDT found that PDT of brain led to increases in EGFR activation [40]. These studies were performed at doses that were insufficient to produce tissue damage and there was no change in total EGFR levels, as we found in the present study
Summary
Photodynamic therapy (PDT) of tumors can provide a means to eradicate residual disease that is unresectable for reasons that may include a lack of detectability (i.e., microscopic disease), broad area of superficial involvement, or localization adjacent to vital structure. One example includes cavitory PDT after resection of malignant brain tumors [1]. This approach has been extended to even more complex geometries, such as PDT of the peritoneal cavity or the thoracic cavity after surgical removal of gross macroscopic disease [2,3,4]. The intraoperative application of PDT to a surgical cavity involves significant technical challenges in delivering light to an irregular surface. The delivery of PDT to any irregular surface is associated with variability in the fluence rate of illumination incident across the treated tissue [5]. At our institution, a light source is systemically moved throughout the intralipid-filled thoracic or peritoneal cavity in order to deliver PDT to serosal malignancies [6]. The disease-laden tissue is exposed to a range of fluence rates over the course of treatment [7]
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