5-Aminolevulinic acid (ALA) and its applications in neurosurgery

Delta-aminolevulinic acid (ALA) is a precursor of the synthesis of porphyrins including heme produced in all mammalian cells. Exogenous ALA induces selective accumulation of the other heme precursor, protoporphyrin IX (PpIX), in neoplastic cells, such as those of malignant gliomas. Upon exposure to violet-blue light PpIX becomes activated, which results in red-light fluorescence as well, as in photodynamic oxidations which may be lethal to the cells. In neurosurgery ALA is used for intraoperative labeling of the border regions of malignant gliomas infiltrated by alive clonogenic tumor cells (ALA-PDD), and is helpful in precise resection of these regions. Clinical data indicate that ALA-PDD-assisted resection of malignant gliomas may result in statistically significant prolongation of postoperative survival. Ongoing research concentrates also on the use of ALA for a selective elimination of glioma cells in situ, and on lipophilic ALA derivatives with more favorable pharmacokinetic properties.