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 red blood pigment. The synthesis of 5-ALA is regulated by an intracellular pool of free heme through a negative feedback mechanism. Administration of an excess of exogenous 5-ALA bypasses the negative feedback control, resulting in selective accumulation of protoporhyrin 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).
The fluorescence property of PPIX is used in fluorescence diagnostics for visualization of malignant gliomas (WHO grade III-IV). Here, the violet-blue illumination of PPIX results in bright red-pink fluorescence in tumor tissue, which can be more accurately removed compared to blue-appearing normal tissue. The use of special filter technologies in neurosurgical operating microscopes makes this fluorescence-assisted surgery possible.
Due to the increased penetration depth of red light (λ =635 nm) compared to light with shorter wavelengths, red light is used for photodynamic therapy (PDT). Excitation of PPIX with red light results in the formation of reactive oxygen species. These species, mainly singlet oxygen, damage the target cells and eventually lead to cell death.