Photodynamic therapy (
PDT) has been used for many years for both palliative and curative treatment of
bronchial carcinomas. However, prolonged skin
phototoxicity and reduced depth of penetration has limited the widespread use of
PDT. We studied the endobronchial
phototoxicity of a novel
photosensitizer,
WST 09 (
Tookad). Fourteen pairs of Large White-Landrace male piglets were given intravenous
WST 09 followed by
laser light illumination of the left mainstem bronchus. Different settings for light dose (fluence), fluence rate (FR),
drug dose (D) and
drug-light interval (DLI) were applied to each pair. Bronchial toxicity was assessed with repeat bronchoscopic photographic evaluation as well as by pathologic examination following autopsy. Animals developed no toxicity, moderate toxicity or severe toxicity. Increased toxicity was seen with increasing D and fluence and decreasing DLI, whereas no increased toxicity was seen with higher FR.
PDT-related histological changes in the normal bronchus confirm the vascular effect of
WST 09. Depending on the parameter settings for fluence, D and DLI, the lesions ranged from focal intramucosal
ischemia to transmural
infarction with subsequent acute
inflammation and
fibrosis. Clinically feasible parameters for
drug and light dosimetry were documented. These data will be important in determining safe starting doses for human phase I/II studies.