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


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.
Furukawa
K
K
Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York 14263 USA.
Yamamoto
H
H
Crean
D H
DH
Kato
H
H
Mang
T S
TS
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002610:Cheek; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006224:Cricetinae; D005453:Fluorescence; D007834:Lasers; D008297:Male; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*
D002273:Carcinogens; D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D015127:9,10-Dimethyl-1,2-benzanthracene