title: Assessment of cutaneous photosensitivity of TOOKAD (WST09) in preclinical animal models and in patients.
abstract: TOOKAD (WST09) is a new, long-wavelength palladium bacteriopheophorbide photosensitizer that targets tissue vasculature. The cutaneous phototoxicity of TOOKAD was assessed in normal rat and pig animal models and in patients in a Phase-I trial of TOOKAD-mediated photodynamic therapy (PDT) for recurrent prostate cancer. Controlled skin exposures were administered using solar-simulated light at various times after drug administration. Two different spectral ranges were used. In the first, the UV portion of the spectrum was removed (UV(-)) because UV irradiation in nondrugged control animals produced an erythema response at incident energy densities (J/cm(2)) lower than those required to induce a PDT response. In the second, the full solar spectrum (UV(+)) was used, and the potentiation by the photosensitizer of the UV-mediated minimum erythema dose was assessed. Results showed that the PDT skin response was negligible at clinical drug doses of 2 mg/kg for any period after administration at light doses of 128 J/cm(2) in the animal models. In patients, there was no observed UV(-) skin response at doses of up to 2 mg/kg, drug-light intervals of 1-3 h or greater and light exposures up to 128 J/cm(2). At higher drug doses in the rat and pig models, the duration of skin phototoxicity was found to be approximately 3 h and less than 1 h, respectively. Using the full spectrum of solar-simulated light, the presence of TOOKAD did not measurably enhance the UV(+)-induced erythema in the rats, pigs or patients.
authors.affiliation: Laboratory for Applied Biophotonics, University Health Network, Toronto, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weersink
authors.forename: Jason
authors.initials: J
authors.lastname: Forbes
authors.forename: Stuart
authors.initials: S
authors.lastname: Bisland
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.forename: Mostafa
authors.initials: M
authors.lastname: Elhilali
authors.forename: Pierre H
authors.initials: PH
authors.lastname: Brún
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001429:Bacteriochlorophylls / Q000494:pharmacology*; D006801:Humans; D023421:Models, Animal; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C456120:palladium-bacteriopheophorbide