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Assessment of Cutaneous Photosensitivity of TOOKAD (WST09) in Preclinical Animal Models and in Patients ¶
Author(s) -
Weersink Robert A.,
Forbes Jason,
Bisland Stuart,
Trachtenberg John,
Elhilali Mostafa,
Brún Pierre H.,
Wilson Brian C.
Publication year - 2005
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2005.tb01528.x
Subject(s) - phototoxicity , photosensitizer , erythema , photodynamic therapy , photosensitivity , action spectrum , medicine , dermatology , skin cancer , irradiation , drug , pharmacology , chemistry , cancer , photochemistry , materials science , optoelectronics , in vitro , biochemistry , organic chemistry , physics , nuclear physics
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 ∼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.