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: Robert A Weersink, Jason Forbes, Stuart Bisland, John Trachtenberg, Mostafa Elhilali, Pierre H Brún, Brian C Wilson
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2005 Jan-Feb Vol. 81 Issue 1 Pg. 106-13 ISSN: 0031-8655 [Print] United States
• PMID: 15382963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bacteriochlorophylls
• Photosensitizing Agents
• palladium-bacteriopheophorbide

Topics

• Animals
• Bacteriochlorophylls (pharmacology)
• Humans
• Models, Animal
• Photosensitizing Agents (pharmacology)
• Ultraviolet Rays