ABSTRACT
BACKGROUND AND OBJECTIVE: Photodynamic therapy has been shown to be an effective treatment modality for surface-oriented neoplasms of the skin, respiratory, gastrointestinal, and urogenital systems. The purpose of this study was to assess the safety and efficacy of photodynamic therapy using a new photosensitizer in the treatment of squamous cell carcinomas of the feline facial skin. STUDY DESIGN/MATERIALS AND METHODS: Cats with naturally occurring squamous cell carcinomas of the facial skin were entered into the study. Tumors were staged using a modification of the World Health Organization (WHO) system for classification of feline tumors of epidermal origin. Photodynamic therapy was delivered to the tumors using an argon-pumped dye laser 24 hours after the administration of the photosensitizer pyropheophorbide-alpha-hexyl-ether (HPPH-23). Following treatment, tumors were evaluated for complete response rates and local control durations. RESULTS: Fifteen tumors were staged T1a (< 1.5 cm diameter, noninvasive), 18 T1b (< 1.5 cm, invasive), and 28 T2B (> 1.5 cm, invasive). Complete response rates as well as local control durations were significantly (P < 0.05) related to stage. Complete response was achieved in 100% of T1a tumors, 56% of T1b tumors, and 18% of T2b tumors. One-year local control rates were 100% for T1a tumors and 53% for T1b tumors; overall 1-year local control rate for all treated tumors was 62%. Clinical, hematological, and biochemical evidence of toxicity was not seen in any cat following drug administration. However, morbidity was observed following treatment of large, invasive tumors of the nasal plane. CONCLUSION: Photodynamic therapy with the photosensitizer HPPH-23 was safe and effective in treating early stage squamous cell carcinomas of the feline nasal plane and facial skin. However, toxicity was encountered following treatment of large neoplasms.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Chlorophyll/analogs & derivatives , Photochemotherapy , Photosensitizing Agents/therapeutic use , Skin Neoplasms/drug therapy , Animals , Carcinoma, Squamous Cell/pathology , Cats , Chlorophyll/adverse effects , Chlorophyll/therapeutic use , Edema/etiology , Inflammation , Opportunistic Infections , Photochemotherapy/adverse effects , Photosensitizing Agents/adverse effects , Skin Neoplasms/pathologyABSTRACT
The in vitro cell survival, localization and ultrastructural changes following irradiation were examined in 9L glioma cells sensitized with a new photosensitizer, lysyl chlorin p6 (LCP). In clonogenic assays, LCP was 10-100-fold more phototoxic than photofrin II on a microgram/mL basis. Lysyl chlorin p6 uptake was blocked when cells were incubated at 2 degrees C. In view of the chemical properties of LCP, this finding indicates that uptake probably occurred through the endocytic pathway. Fluorescence studies showed LCP localized in a region of the endocytic compartment similar in size, shape and distribution to that labeled by lucifer yellow CH (LY), as well as localizing diffusely throughout the perinuclear cytoplasm. Cells stained with both LY and LCP, however, had distinctly separate regions of staining. Lysyl chlorin p6 localization differed from that of fluorescent probes labeling the mitochondria, Golgi apparatus and endoplasmic reticulum. Ultrastructural changes at both 2 and 30 min after laser irradiation were similar. Mitochondria were often condensed or swollen and also had constrictions and cytoplasmic invaginations. The Golgi apparatus, perinuclear space and rough endoplasmic reticulum (RER) were dilated. These data demonstrate that LCP localizes in a portion of the endosomal compartment, but that morphologic damage initially occurs in the mitochondria, Golgi apparatus and RER.
Subject(s)
Dihematoporphyrin Ether/pharmacology , Glioma/therapy , Lysine/analogs & derivatives , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Animals , Cell Survival , Cytoplasm/radiation effects , Dihematoporphyrin Ether/toxicity , Dose-Response Relationship, Radiation , Glioma/ultrastructure , Intracellular Membranes/radiation effects , Lasers , Light , Lysine/pharmacology , Lysine/toxicity , Microscopy, Electron , Microscopy, Fluorescence , Mitochondria/radiation effects , Photosensitizing Agents/toxicity , Porphyrins/toxicity , Rats , Tumor Cells, CulturedABSTRACT
The effects of photodynamic therapy (PDT) on normal brain tissue and depth of brain necrosis were evaluated in rats receiving 2.5 mg/kg aluminum phthalocyanine tetrasulfonate. Twenty-four hours later brains were irradiated with 675 nm light at a power density of 50 mW/cm2 and energy doses ranging from 1.6 to 121.5 J/cm2. Brains were removed 24 h after PDT and evaluated microscopically. When present, brain lesions consisted of well-demarcated areas of coagulation necrosis. When plotting the depth of necrosis against the natural log of energy dose, the data fit a piecewise linear model, with a changepoint at 54.6 J/cm2 and an x intercept of 7.85 J/cm2. The slopes before and after the changepoint were 2.04 and 0.21 mm/ln J cm-2, respectively. The x intercept suggests a minimum light dose below which necrosis of normal brain will not occur, whereas the changepoint indicates the energy density corresponding to an approximate maximum depth of necrosis.
