Medical applications of topical PDT

July 1, 2007

Photodynamic therapy is becoming a very popular treatment modality for a number of indications - from actinic keratoses and nonmelanoma skin cancers to acne, rosacea and photorejuvenation. Mixing and matching skin preparation, the length of time for which ALA is applied and the appropriate light source are keys to maximizing results.

Buffalo, N.Y. - The indications for photodynamic therapy (PDT) are steadily evolving and growing, as physicians discover medical applications for this novel therapeutic modality, according to one expert.

Understanding and mastering PDT dosimetry for customizing therapies is crucial in maximizing positive therapeutic outcomes, says Allan R. Oseroff, M.D., Ph.D., professor and chairman of the departments of dermatology, Roswell Park Cancer Institute and the University at Buffalo School of Medicine and Biomedical Sciences.

PDT with topical aminolevulinic acid (ALA) is used to treat actinic keratoses, nonmelanoma skin cancers (mostly basal cell carcinomas and Bowen's disease), and cutaneous T-cell lymphoma, as well as many other skin conditions, including acne, rosacea, hidradenitis suppuritiva, scleroderma and erosive lichen planus.

"When using photodynamic therapy, the physician must aim to individualize treatment regimens according to the disease or condition, the patient and the tolerance of the side effects. The outcomes depend on the dose of PDT, which is proportional to the product of the protoporphyrin-IX (PpIX) photosensitizer concentration and the absorbed light. Thus, PDT doses can be customized by controlling the amount of ALA that enters the skin, the length of time allowed for PpIX synthesis, the amount of light that is absorbed, as well as the rate that the light is delivered to the area," Dr. Oseroff tells Dermatology Times.

Physiological factors

He says several factors determine the amount of ALA that enters the skin. The skin's permeability can be increased by physical removal or disruption of the stratum corneum using abrasion or curettage, or through dilapidation with acetone.

With Levulan Kerastick (Dusa), which delivers ALA in solution, the ALA stops entering the skin when the solution dries, so ALA levels can be increased by multiple applications and by occlusion.

According to Dr. Oseroff, the longer ALA is left on the skin, the more PpIX is synthesized. The hydrophobic PpIX is made within the mitochondria of epidermally derived and immune cells, but over time it can diffuse to other cells and to lipophilic sites such as the stratum corneum.

Dr. Oseroff says the absorbed light dose depends on the color of light used. He adds that the BLU-U light (412-422 nm) is very efficiently absorbed by PpIX, so a delivered light dose of 10 J/cm2 at 10 mW/cm2 can give a high PDT dose for superficial lesions lying above the dermal blood supply.

Conversely, a 595 nm light from a pulsed dye laser (PDL) or 560 to 1,200 nm light from an intense pulsed light source (IPL) are poorly absorbed by PpIX, so these devices tend to give low PDT doses, although the longer-wavelength light has better penetration into the skin.

Tailoring treatment

"Photodynamic therapy dose and dose rate are adjustable through choices of skin preparation, ALA application time, occlusion, as well as wavelengths of light and irradiance. Physicians can match therapies by orchestrating these variables to the specific lesion to be treated," Dr. Oseroff says.

In general, a high PDT dose would be a 12-hour to 24-hour application time for ALA, using a BLU-U light source. A moderate PDT dose could be a 12- to 24-hour application of ALA using a PDL or IPL, or a three- to four-hour application of ALA using a BLU-U light. Low doses to very low doses can be achieved with 30- to 90-minute ALA applications and blue light, while the same application times with the IPL or PDL give even lower PDT doses.

Actinic keratoses on the face respond well to low-dose PDT with minimal skin preparation, while more hyperkeratotic lesions on the extremities generally require skin preparation and higher-dose treatment.

Tread lightly - when appropriate

According to Dr. Oseroff, high-dose PDT primarily kills the target cells, which is appropriate for carcinomas and other significant disease.