What are the details of photodynamic therapy (PDT)?

Photodynamic Therapy: Mechanism, Applications, and Clinical Details

Photodynamic therapy (PDT) is a non-invasive treatment modality that uses photosensitizing agents, light activation, and oxygen to selectively destroy abnormal cells through a photochemical reaction that generates cytotoxic reactive oxygen species. 1

Mechanism of Action

PDT requires three key components to work effectively:

1. Photosensitizer: Most commonly 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL)
2. Light source: Specific wavelength to activate the photosensitizer
3. Oxygen: Required for the photodynamic reaction

The process works through the following steps:

• The photosensitizer is applied topically to the target area
• The photosensitizer is preferentially accumulated in abnormal/target cells
• When exposed to specific wavelengths of light, the photosensitizer becomes activated
• The activated photosensitizer transfers energy to oxygen molecules, creating reactive oxygen species (primarily singlet oxygen)
• These reactive oxygen species cause cellular damage and death of the target cells 1, 2

ALA and MAL work as prodrugs that are converted within cells to protoporphyrin IX (PpIX), which is the actual photoactive compound. The preferential accumulation in abnormal cells occurs due to:

• Increased penetration through abnormal epidermis
• Preferential intracellular accumulation in proliferating, relatively iron-deficient cells 1

Light Sources for PDT

Several light sources can be used for PDT activation:

Light Source Type	Wavelength (nm)	Notes
Lasers (various)	630	Deeper penetration, requires laser safety protocols
LED arrays	630 ± 5	Compact, targeted delivery
Metal halide	600-750	Suited for large treatment areas
Fluorescent	417 ± 5	Targets superficial lesions
Daylight	Natural spectrum	Used in daylight PDT, less painful

The choice of light source depends on the:

• Target lesion depth (red light at 630nm penetrates deeper than blue light at 400-500nm)
• Treatment area size
• Equipment availability 1

FDA-Approved Applications

PDT is FDA-approved for:

1. Actinic keratoses (AK) on face and scalp

   • Using ALA (Levulan®, Ameluz®) or MAL (Metvixia®)
   • Particularly effective for multiple lesions and field treatment

2. Superficial and nodular basal cell carcinomas (BCC)

   • Using MAL (Metvixia®) for BCCs unsuitable for conventional therapy
   • Most effective for superficial BCCs 1, 2, 3

3. Squamous cell carcinoma in situ (Bowen's disease)

   • Using MAL (Metvixia®) 1

Clinical Protocol for PDT

The standard PDT procedure involves:

1. Lesion preparation:

   • Degreasing the skin with alcohol
   • Gentle removal of scales/crusts
   • Roughening of lesion surface to enhance penetration 3

2. Photosensitizer application:

   • Apply approximately 1mm thick layer to target area
   • Include 5mm of surrounding skin
   • Allow to dry for approximately 10 minutes 2, 3

3. Occlusion period:

   • Cover with light-blocking occlusive dressing
   • Wait 3-4 hours for optimal photosensitizer conversion 2, 3

4. Light illumination:

   • Remove dressing and any remaining gel
   • Illuminate with appropriate light source
   • Standard dose is approximately 37 J/cm² for red light
   • Treatment time varies by light source 3

Advantages of PDT

PDT offers several advantages over conventional treatments:

• Relatively selective treatment of abnormal tissue
• Minimal or no scarring with excellent cosmetic outcomes
• Non-invasive procedure
• Ability to treat multiple lesions simultaneously
• Outpatient procedure
• Possibility for repeated treatments 1

Limitations and Side Effects

Common side effects include:

• Pain during illumination: More significant with conventional PDT than daylight PDT
• Erythema and edema: Usually resolves within days
• Crusting and scaling: Temporary
• Photosensitivity: Patients should avoid sun exposure for 24-48 hours after treatment

PDT has limited efficacy for:

• Thick nodular BCCs (unless combined with prior debulking)
• Invasive squamous cell carcinomas 1

Emerging Applications

While not yet FDA-approved, PDT shows promise for:

• Photorejuvenation: Improving signs of skin aging including fine wrinkles, roughness, and mottled pigmentation
• Acne: Targeting P. acnes bacteria and sebaceous glands
• Viral warts: Particularly recalcitrant cases
• Psoriasis: As an alternative treatment option
• Cutaneous T-cell lymphoma: Early research shows potential 1, 4, 5

Treatment Considerations

For optimal outcomes:

• Patient selection: Best results in non-hyperkeratotic lesions
• Lesion preparation: Gentle debridement improves photosensitizer penetration
• Treatment area: Maximum recommended area is 60 cm² per session
• Retreatment: Consider retreating lesions that haven't completely resolved after 3 months 3

PDT represents an important treatment option for various dermatologic conditions, particularly for patients with multiple lesions, lesions in cosmetically sensitive areas, or when conventional treatments are contraindicated.