WHAT IS PHOTODYNAMIC THERAPY
AND HOW DOES IT WORK?

PDT requires all three components to work. Remove any one, and cell death does not occur. This interdependence is what gives PDT its selectivity — light can be aimed precisely, and without light there is no toxicity regardless of how much photosensitiser is present.

“PDT is activation therapy, not direct toxicity. The drug alone does nothing. The light alone does nothing. Together, with oxygen, they create a lethal reaction precisely where it's needed.”

• Component 1: The Photosensitiser

  A drug administered intravenously (systemic photosensitisers like Photofrin) or applied topically to skin (ALA, MAL). The photosensitiser accumulates preferentially in rapidly dividing tumour cells over several hours to days. Critically, normal cells clear the photosensitiser faster than tumour cells — creating a window of tumour selectivity.

• Component 2: The Light Source

  A specific wavelength of light matched to the photosensitiser's absorption peak — typically red or near-infrared light (630–760 nm for Photofrin; 635 nm for ALA; 652 nm for MAL). Delivered via laser fibre through an endoscope for internal tumours, or via LED/lamp panels for skin lesions. The light activates only the photosensitiser, not surrounding tissue.

• Component 3: Molecular Oxygen

  Oxygen in the target tissue is essential for the photochemical reaction. When the activated photosensitiser transfers energy to molecular oxygen, it generates singlet oxygen and other reactive oxygen species (ROS) — the primary toxic mediators. Hypoxic tumour areas respond less well to PDT, which is a known limitation for advanced bulky tumours.

PDT kills tumour cells through three simultaneous mechanisms — direct cytotoxicity, vascular damage, and immune activation. Together, these create durable local tumour control.

• Direct Tumour Cell Destruction

  Singlet oxygen generated within the tumour cell attacks cell membranes, mitochondria, and the endoplasmic reticulum — causing rapid cell death through apoptosis and necrosis. Because singlet oxygen has a very short diffusion range (<20 nm), the damage is highly localised to cells that contain the photosensitiser.

• Vascular Shutdown

  PDT damages the blood vessels supplying the tumour — causing vasoconstriction, platelet aggregation, and ultimately vascular thrombosis that cuts off the tumour's blood supply. This secondary mechanism extends cell death beyond the immediate photosensitiser distribution, contributing to larger ablation volumes than direct cytotoxicity alone.

• Immune Activation

  PDT triggers an acute inflammatory response and stimulates tumour antigen presentation. Damage-associated molecular patterns (DAMPs) released by dying tumour cells activate dendritic cells and cytotoxic T lymphocytes. In some patients, this immune activation contributes to control of distant disease — an abscopal-like effect being actively studied.

Cancers and pre-cancerous conditions for which PDT has regulatory approval (FDA, EMA, or equivalent) and established clinical evidence.

PDT occupies a distinct niche — particularly valuable where its specific characteristics align with clinical need.

• PDT vs Surgery

  PDT preserves organ structure and function. In the oesophagus, it removes tumour without removing the organ. In the lung, it ablates endobronchial disease without thoracotomy. PDT is less effective for large, deeply invasive tumours where surgical margins matter. Surgery provides definitive pathological margin assessment; PDT does not.

• PDT vs Chemotherapy

  PDT is a local treatment — it acts only where light is delivered. Chemotherapy is systemic — treating the whole body. PDT does not have the systemic toxicity of chemotherapy (no nausea, no hair loss, no myelosuppression) but cannot address metastatic disease. The two can be combined — PDT for local disease, chemotherapy for systemic control.

• PDT vs Radiotherapy

  Both PDT and radiotherapy can be used for local tumour control. Key PDT advantages: no radiation dose accumulation (can be repeated unlimited times), no risk of radiation-induced secondary cancers, faster recovery. Key limitations: PDT requires light delivery access (endoscopy or skin surface) — not suitable for deeply seated inaccessible tumours. Radiotherapy can treat any location.

PDT is a valuable tool within its scope of use. Understanding its limitations prevents misapplication and ensures appropriate patient selection.

• What PDT Cannot Do Well

  PDT is limited to sites accessible by light delivery — endoscopy or skin surface. It cannot treat deeply infiltrating tumours (>10 mm from the illuminated surface in most protocols). Large bulky tumours respond poorly because of light penetration limits and tumour hypoxia. It cannot address regional lymph nodes or metastatic disease.

• What PDT Does Well

  PDT excels for mucosal tumours — oesophagus, airways, bile duct, bladder — where light delivery via endoscopy reaches the target. It is particularly valuable where repeated treatment is expected (Barrett's oesophagus, field cancerisation of skin) and where preserving organ function matters. It also fits well in patients who cannot tolerate surgery or radiation.

Learn more about specific photosensitisers, indications, and patient guides.

Frequently Asked Questions

Common questions about what PDT is and how it works.