Photodynamic Therapy - Light, Drug, Action!
Photodynamic therapy (PDT) is a non-invasive treatment using a photosensitizer, specific wavelength light, and oxygen to selectively destroy target cells.
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Key Components (📌 POL):
- Photosensitizer (PS): Drug that absorbs light.
- Light: Activates the PS, typically laser or LED.
- Oxygen ($O_2$): Essential for cytotoxic reactions.
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Mechanism:
- PS absorbs light, enters an excited state.
- Energy transfer to $O_2$ generates Reactive Oxygen Species (ROS).
- Type I reaction: Produces superoxide, hydroxyl radicals.
- Type II reaction: Predominantly generates cytotoxic singlet oxygen ($^1O_2$). The key reaction is $O_2 + h\nu \rightarrow ^1O_2$.
- ROS cause cellular damage and apoptosis/necrosis.

⭐ PDT's efficacy largely stems from Type II photoreactions generating cytotoxic singlet oxygen.
Photodynamic Therapy - Sensitizers & Spectra
- Photosensitizers: Absorb light, produce cytotoxic reactive oxygen species.
- 1st Generation: e.g., Porfimer sodium.
- 2nd Generation: Improved properties (e.g., ALA, MAL, Verteporfin).
⭐ 5-ALA is a prodrug converted intracellularly to Protoporphyrin IX (PpIX), the active photosensitizer.

| Photosensitizer | Type | Admin. | Activation (nm) | Incubation | Penetration (Light) |
|---|---|---|---|---|---|
| 5-ALA | Prodrug (PpIX) | Topical | 400-420 (blue), 630-635 (red) | 1-18h | Superficial, Deeper |
| MAL | Prodrug (PpIX), lipophilic | Topical | 630-635 (red) | 3h | Deeper |
| Porfimer Sodium | 1st Gen | IV | 630 (red) | N/A | Deeper |
| Verteporfin (AMD) | 2nd Gen | IV | 689-692 (deep red) | N/A | Deepest |
- **Lasers:** Monochromatic (e.g., Diode **630-690 nm**).
- **LEDs:** Narrowband (Blue **~417 nm** for superficial ALA; Red **~633 nm** for ALA/MAL).
- **IPL/Broadband Lamps:** Filtered to specific wavelengths.
Photodynamic Therapy - Skin Savers
PDT: Photosensitizer (ALA, MAL) + Light + $O_2$ $\rightarrow$ Reactive Oxygen Species ($O_2^-$) $\rightarrow$ Selective cell kill.
📌 Key Indication Mnemonic: PDT Acts on Bad Cells (Actinic Keratosis, Basal Cell Carcinoma, Bowen's Disease).
Key Indications:
| Condition | Photosensitizer(s) | Light Source(s) | Key Notes |
|---|---|---|---|
| Actinic Keratoses (AKs) | ALA, MAL | Blue light, Red light | Field treatment for widespread lesions. High efficacy. |
| Superficial BCC (sBCC) | MAL | Red light | For lesions <2 mm thick; good cosmesis. |
| Bowen's Disease (SCC in situ) | MAL, ALA | Red light | Effective for larger, superficial areas. |
- Acne vulgaris (ALA; Blue/Red light)
- Photorejuvenation (ALA; IPL, Red/Yellow light)
- Warts (various agents)
- Cutaneous leishmaniasis
⭐ PDT is FDA-approved for actinic keratoses and often preferred for widespread lesions due to field treatment capability.
A
Photodynamic Therapy - Zap & Aftercare
- Mechanism: Photosensitizer + Light + $O_2$ $\rightarrow$ Reactive Oxygen Species (ROS) $\rightarrow$ Selective cell kill.
- Advantages: Non-invasive, targeted therapy, excellent cosmesis, repeatable, effective for field cancerization (multiple lesions).
- Disadvantages: Significant pain/burning during illumination, post-procedure photosensitivity (sun avoidance 24-48 hours), higher cost vs. some alternatives, limited tissue penetration depth (superficial lesions).
⭐ Pain during PDT illumination is a significant limiting factor, often managed with cooling, analgesia, or interruptions.
- Common Side Effects & Aftercare:
- Strict sun/bright light avoidance for 24-48 hours is crucial.
- Expected: Erythema, edema, crusting, peeling, pustules, localized pain/itching. Manage with cool compresses, emollients.

- Contraindications: Porphyria (absolute), known allergy to photosensitizer or its components, pregnancy (relative).
High‑Yield Points - ⚡ Biggest Takeaways
- PDT mechanism: Photosensitizer + light + oxygen → singlet oxygen → selective cell death.
- Photosensitizers: ALA & MAL (prodrugs) convert to Protoporphyrin IX (PpIX), the active compound.
- Light: Blue light (superficial lesions like AKs), Red light (deeper lesions like sBCC).
- Primary uses: Actinic keratosis, Bowen's disease, superficial BCC; also for acne.
- Benefits: Non-invasive, good cosmesis, treats field cancerization.
- Adverse effects: Pain during procedure, photosensitivity, erythema, edema post-treatment.
- Avoid in: Porphyrias.
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