Thermal Ultra Short Photodynamic Therapy: Heating Fibroblasts During Sub-30-Minute Incubation of 5-Aminolevulinic Acid Increases Photodynamic Therapy-Induced Cell Death

BACKGROUND: Actinic keratoses (AKs) prevalence was estimated at 39.5 million Americans in 2004, and the cost to treat AKs that year was approximately 1 billion dollars. Photodynamic therapy (PDT) is an FDA-approved therapy for the treatment of AK. Recent studies have focused on reducing PDT treatment time while maintaining efficacy.

OBJECTIVE: To investigate the use of thermal modulation to improve the efficacy of ultra short aminolevulinic acid (ALA) incubation PDT.

MATERIALS AND METHODS: Human dermal fibroblasts (HDFs) were incubated for 10, 15, or 20 minutes with 0.5-mM ALA at various temperatures (21, 24, 27, 30, 33, 36, 39, and 42°C). After ALA incubation, samples were treated for 1,000 seconds with blue light (417 ± 5 nm) resulting in a fluence of 10 J/cm. Samples were collected and stained for apoptosis/necrosis with annexin-V and 7-aminoactinomycin D (7-AAD), then analyzed by flow cytometry.

RESULTS: Human dermal fibroblast treated with 10-minute ALA-PDT had no statistically significant changes in apoptosis at all temperatures. Human dermal fibroblast treated with 15- or 20-minute ALA-PDT had statistically significant increases in apoptosis at 39 and 42°C (p < .05).

CONCLUSION: These results suggest the use of thermal modulation may improve ultra short ALA incubation PDT efficacy.