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Tissue Distribution and Photosensitizing Properties of Mono-L-aspartyl Chlorin e6 in a Mouse Tumor Model¹

Clayton Ocular Oncology Center, Childrens Hospital of Los Angeles [C. J. G., A. F.], and Departments of Pediatrics and Radiation Oncology, University of Southern California School of Medicine [C. J. G.], Los Angeles, California 90027

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm which are potentially exploitable for photodynamic therapy (PDT). The current investigation examined pharmacological and photosensitizing parameters of NPe6 in tumor and normal tissues in mice. [¹⁴C]NPe6 was used to obtain quantitative tissue distributions of the photosensitizer as a function of: (a) time following administration; (b) drug dose; (c) mode of drug administration; and (d) tumor size. The in vivo photosensitizing efficiency of NPe6 was compared directly to Photofrin II in experiments which evaluated tumor responses and induction of normal skin damage. Initial PDT experiments demonstrated that NPe6 was ineffective at inducing tumor cures when a 24-h time interval (between drug administration and light treatment) was used. However, PDT-induced tumor cures were obtained when NPe6 was administered 4–6 h prior to light exposure, and these NPe6-PDT treatment parameters were as effective as standard Photofrin II-mediated PDT. Interestingly, the level of PDT-induced normal skin damage was significantly greater for Photofrin II than for NPe6 at comparable drug and light doses. An analysis of pharmacological data and PDT time interval requirements suggests that plasma concentrations of NPe6 may be a more important predictive factor than tumor tissue levels of the photosensitizer for the production of PDT-mediated tumor cures. The results of this investigation indicate that NPe6 is an effective tumor photosensitizer with in vivo clearance properties that eliminate the side effect of prolonged normal skin photosensitization.

¹ This investigation was performed in conjunction with the Clayton Foundation for Research and was supported in part by a contract from Nippon Petrochemicals Co., Ltd., and by United States Public Health Service Grants R37-CA-31230 and R01-CA-44733 awarded by the National Cancer Institute, Department of Health and Human Resources.

² To whom requests for reprints should be addressed, at Childrens Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027.

Received 12/13/89. Revised 3/16/90.

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