ATC Group: L01XD Sensitizers used in photodynamic/radiation therapy

5-Aminolevulinic acid (5-ALA) is a natural biochemical precursor of heme that is metabolised in a series of enzymatic reactions to fluorescent porphyrins, particularly PPIX. 5-ALA synthesis is regulated by an intracellular pool of free heme via a negative feedback mechanism. Administration of excess exogenous 5-ALA avoids the negative feedback control, and accumulation of PPIX occurs in target tissue. In the presence of visible light, fluorescence of PPIX (photodynamic effect) in certain target tissues can be used for photodynamic diagnosis.

Methyl aminolevulinate is a prodrug that is metabolized to protoporphyrin. After topical application of methyl aminolevulinate, porphyrins accumulate intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells.

Padeliporfin is retained within the vascular system. When activated with 753 nm wavelength laser light, padeliporfin triggers a cascade of pathophysiological events resulting in focal necrosis within a few days.

Porfimer is a mixture of porphyrin units, which are linked together in chains of two to eight units The cytotoxic actions of porfimer are light- and oxygen-dependent. Photodynamic therapy with porfimer is a 2-stage process. Cellular damage caused by porfimer PDT is a consequence of the propagation of free radical reactions.

Temoporfin is a photosensitising agent used in the photodynamic therapy of tumours.