Photodynamic therapy: a review

Photodynamic therapy (PDT) of malignant tumours is a new technique for treating cancers. After intravenous injection, a photosensitiser is selectively retained by the tumour cells so after time there is more sensitiser in the tumour than in the normal adjacent tissue. The photosensitiser must be able to absorb the wavelength of light being delivered to it, and the amount of light getting to the photosensitiser depends on the characteristics of the tissue it passes through. When exposed to light with the proper wavelength, the sensitiser produces an activated oxygen species, singlet oxygen, that oxidises critical elements of neoplastic cells. Because there is less sensitiser in the adjacent normal tissue, less reaction occurs to it. Since this is an entirely different process, the use of chemotherapy, ionising radiation or surgery does not preclude the use of PDT. Also, unlike ionising irradiation, repeated injections and treatments can be made indefinitely. Different molecules and atoms absorb different wavelengths of energy. Since the light energy must be absorbed to start the photochemical reaction, the absorption spectrum of the photosensitiser determines the wavelength used to initiate the reaction. However, this can be qualified by the tissue the light has to travel through to get to the photosensitiser. The photosensitiser porfimer sodium has a peak absorption in the area of 405 nm (blue-violet) and a much lower absorption peak at 630 nm (red). However, because the longer red wavelength penetrates tissue deeper than 405 nm, we use the red wavelength, usually delivered from a laser system. This permits coupling of the red light beam to quartz fibres which can then be used with modifications to treat external surface tumours, inserted interstitially directly into large tumours, passed though any endoscope to treat intraluminal tumours, or inserted behind the retina to treat tumours of the retina. Twenty years after the pioneering work of Dr. Thomas Doherty, the US Food and Drug Administration (FDA) has approved the use of porfimer sodium for photodynamic therapy of endobronchial and oesophageal tumours. Research continues towards approval for management of skin cancers and metastatic cutaneous and subcutaneous breast cancers. The realisation that one of the mechanisms of photodynamic therapy is thrombosis of vessels led to the development of verteporfin to treat macular degeneration. Multiple other areas are being investigated as well as new photosensitisers. Photodynamic therapy is an entirely new treatment modality and its development can be likened to that of the discovery of antibiotics. This is just the beginning, and its possible uses are only limited by the imagination.