Localization and treatment of transformed tissues using the photodynamic sensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a

Abstract

Background and objective: Photofrin is the photosensitizer currently used in most clinical trials examining the efficacy of photodynamic therapy (PDT) for the treatment and/or palliation of neoplasia. Although this drug has been shown to be efficacious in many of these trials, it possesses less than ideal qualities for use in a systemically administered photosensitizer. A new photosensitizer, 2-[l-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was developed for PDT. HPPH possesses more rapid clearance from skin and greater cytotoxicity per drug dose than Photofrin. The aims of this study were to: (1) examine the uptake and retention of HPPH in tissues undergoing malignant transformation using laser-induced fluorescence, and (2) evaluate the efficacy of HPPH and 665 nm light in treating carcinogen-induced tumors of the hamster buccal cheek pouch.

Study design/materials and methods: The model of tissue transformation was the carcinogen (9,10-dimethyl-1, 2-benzanthracene)-induced premalignant and malignant lesions of the hamster buccal cheek pouch. Following induction of the specific transformation stages, hamsters were injected intraperitoneally with 0.5 mg/kg HPPH. Subsequently, the buccal mucosa was examined for fluorescence at various times up to 72 hours after photosensitizer injection.

Results: Uptake studies of HPPH showed highest fluorescence levels in tissues 48 hours after HPPH injection. Fluorescence levels of tissues increased significantly as follows. Normal < dysplasia < papillomas < squamous cell carcinomas. Carcinogen-induced tumors in 14 hamsters were treated with surface illuminations of red light (665 nm) via fiber optics coupled to an argon-ion pumped dye laser 48 hours after intraperitoneal injection with either 0.5 or 1.0 mg/kg HPPH. Complete necrosis of tumor tissues 7 days following PDT was observed in 57% (4/7) with 0.5 mg/kg and 86% (6/7) with 1.0 mg/kg HPPH.