What is Photodynamic Therapy (PDT)?

What is Photodynamic Therapy (PDT)?

Photodynamic therapy (PDT) is a minimally invasive treatment that uses a photosensitizing drug combined with light of a specific wavelength to selectively destroy abnormal cells through the generation of reactive oxygen species, primarily singlet oxygen. 1

Fundamental Mechanism

PDT requires three essential elements working together 1:

• Photosensitizer: A light-activated drug that accumulates preferentially in abnormal or rapidly proliferating cells 1
• Light source: Specific wavelength light (typically 600-800 nm, the "therapeutic window") that activates the photosensitizer 1
• Oxygen: Must be present in tissue for the cytotoxic reaction to occur 1

How PDT Works

The therapeutic process occurs through a photochemical reaction 1:

• The photosensitizer is applied topically or administered intravenously, then selectively accumulates in target tissue 1
• When exposed to light at the appropriate wavelength, the photosensitizer absorbs photons and becomes excited from its stable ground state to an unstable singlet state, then to a longer-lived triplet state 1
• The activated photosensitizer transfers energy to molecular oxygen, generating reactive oxygen species (ROS), particularly singlet oxygen 1
• ROS are highly cytotoxic with a very short lifetime (<0.04 microseconds) and limited radius of action (<0.02 micrometers), causing localized cell death 1

Mechanisms of Tumor Destruction

PDT destroys abnormal tissue through three primary pathways 2, 3:

• Direct cellular damage: Apoptosis and necrosis of target cells through oxidative stress 1
• Vascular shutdown: Damage to tumor microvasculature causing ischemia 2, 3
• Immune activation: Induction of local inflammatory and immune responses against tumor cells 1

Common Photosensitizers

The most widely used photosensitizers in clinical practice include 1, 4, 5:

• 5-Aminolevulinic acid (ALA): A second-generation photosensitizer with low molecular weight, short phototoxicity period (24-48 hours), and good tissue penetration 1
• Methyl aminolevulinate (MAL): Licensed for non-hyperkeratotic actinic keratoses, squamous cell carcinoma in situ, and superficial basal cell carcinomas 1, 5
• BF-200 ALA (Ameluz): A nanoemulsion formulation of ALA licensed for actinic keratoses on face and scalp, and recently for basal cell carcinoma 1, 4

These are prodrugs that are converted intracellularly to protoporphyrin IX (PpIX), the active photosensitizer 1, 5

Light Sources

Multiple light sources can activate photosensitizers 1:

• LED sources: Emit narrow-spectrum light centered around 630-635 nm, matching the activation peak of PpIX; virtually maintenance-free and cost-effective 1
• Laser diodes: Provide coherent monochromatic light delivered via optical fiber, allowing precise dosimetry calculation 1
• Blue fluorescent lamps: Peak emission at 410-417 nm, routinely used for actinic keratoses in the U.S. 1
• Daylight: Natural daylight can be used as a light source for daylight-PDT, which is nearly pain-free compared to conventional PDT 1, 6

Red light (630 nm) penetrates deeper into tissue than blue light and is superior for treating basal cell carcinoma and Bowen's disease, while blue light is effective for superficial actinic keratoses 1

Clinical Applications

PDT is approved and used for 1, 2, 7:

• Dermatology: Actinic keratoses, basal cell carcinoma, squamous cell carcinoma in situ, and skin rejuvenation 1
• Oral medicine: Oral leukoplakia and potentially malignant oral disorders 1
• Pulmonology: Endobronchial malignancies when administered via bronchoscopy 1
• Gastroenterology: Early esophageal and gastrointestinal cancers 7
• Other: Bladder cancer, gynecological neoplasms, and vascular malformations 2, 7

Treatment Protocol

Standard PDT procedure involves multiple steps 1, 4:

• Lesion preparation: Remove surface scales, crusts, and debris to enhance photosensitizer penetration 1, 4
• Photosensitizer application: Apply approximately 1 mm thick layer to lesions plus 5 mm surrounding skin 4
• Occlusion period: Cover with light-blocking dressing for 3 hours (for ALA) to allow conversion to active photosensitizer 4, 5
• Illumination: Remove dressing and excess gel, then immediately illuminate with appropriate light source at specified dose (typically 37-75 J/cm²) 4, 5
• Post-treatment protection: Avoid sunlight and intense light for 48 hours 4

For actinic keratoses, one treatment session is typically used, while basal cell carcinoma and squamous cell carcinoma in situ require two treatments 7 days apart 1

Advantages Over Conventional Treatments

PDT offers several distinct benefits 7, 3:

• Selectivity: Preferentially destroys abnormal cells while sparing normal tissue 1
• Repeatability: Can be performed multiple times at the same site without cumulative toxicity 7
• Minimal systemic toxicity: Low systemic effects compared to chemotherapy 2, 3
• Excellent cosmetic outcomes: Minimal scarring and superior functional preservation 1, 7
• No resistance: Lacks intrinsic or acquired resistance mechanisms seen with other treatments 3
• Compatibility: Can be combined with surgery, chemotherapy, or radiation without compromising efficacy 7

Adverse Effects

The most common side effect is treatment-related pain, particularly with conventional high-irradiance PDT 1:

• Pain: Neurogenic and inflammatory components; more severe with larger treatment areas and head/neck locations 1
• Local reactions: Erythema, edema, crusting, and temporary pigmentation changes 1, 8
• Rare complications: Scarring, infection, and prolonged photosensitivity 1

Daylight-PDT has proven to be nearly pain-free compared to conventional PDT, making it preferable for large treatment areas 1, 6

Contraindications

PDT should not be used in patients with 1:

• Porphyria: Genetic disorder affecting porphyrin metabolism 1
• Coagulopathy: Bleeding disorders 1
• Pregnancy: Safety not established 1
• Uncontrolled systemic disease: Severe hypertension, heart disease, diabetes, liver/kidney damage 1
• Photosensitivity disorders: History of allergy to light or porphyrins 1