title: Endobronchial phototoxicity of WST 09 (Tookad), a new fast-acting photosensitizer for photodynamic therapy: preclinical study in the pig.
abstract: 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.
authors.affiliation: Division of Respiratory Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Tremblay
authors.forename: Sylvie
authors.initials: S
authors.lastname: Leroy
authors.forename: Lutz
authors.initials: L
authors.lastname: Freitag
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Pierre-Hervé
authors.initials: PH
authors.lastname: Brun
authors.forename: Charles-Hugo
authors.initials: CH
authors.lastname: Marquette
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D001999:Bronchoscopy / Q000379:methods; D008297:Male; D023421:Models, Animal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000633:toxicity*; D013552:Swine
chemical_list: D017319:Photosensitizing Agents