The 5-aminolevulinic acid (5-ALA) is a naturally occurring amino acid in the human body and occurs as an intermediate in heme synthesis to form the red blood pigment. The synthesis of 5-ALA is regulated via an intracellular pool of free heme through a negative feedback mechanism. Administration of an excess of exogenous 5-ALA bypasses negative feedback control resulting in selective accumulation of protoporphyrin IX (PPIX) in tumor cells such as malignant gliomas or actinic keratoses.
PPIX serves as a so-called photosensitizer, which is illuminated with light of the appropriate wavelength (e.g. λ = 408nm, 506nm, 532nm, 580nm or 635nm).
PPIX is used in fluorescence diagnostics for the visualization of malignant gliomas (WHO grade III-IV). The violet-blue illumination of the PPIX leads to a bright red-pink fluorescence in the tumor tissue, which can be more accurately removed in comparison to the blueish normal tissue. The use of special filter technologies in neurosurgical surgical microscopes allows this fluorescence-based operation.
Because of the increased penetration of red light (λ = 635 nm) compared to light with shorter wavelengths, red light is used for photodynamic therapy (PDT). The excitation of PPIX with red light leads to the formation of reactive oxygen species. These species, mainly singlet oxygen, damage the target cells and finally lead to cell death.