Intraoperative Photodynamic Diagnosis of Brain Tumors Using 5-Aminolevulinic Acid

Abstract

Diagnostic Techniques and Surgical Management of Brain Tumors 228 2. 5-ALA metabolic pathway 2.1 5-ALA metabolism in normal cells 5-ALA is a substance that naturally exists in the body. In the first stage, 5-Ala is produced via the condensation of glycine and succinyl-CoA by ALA synthetase (ALAS) in the mitochondria. This process receives negative feedback from heme, which is the endproduct. 5-ALA is actively transported via cytoplasm. In the next step, porphobilinogen (PBG) is created from ALA via ALA dehydratase. The actions of PBG deaminase (PBGD) and uroporphyrinogen III synthase compress 4 PBG molecules, effectively cyclizing a tetrapyrrole chain and producing uroporphyrinogen III. Uroporphyrinogen III is converted by uroporphyrinogen decarboxylase into coproporphyrinogen III, which is exposed to coproporphyrinogen oxidase in the mitochondrial intermembrane space. Decarboxylation and oxidation of the propionic side chains of the vinyl groups' rings A and B ultimately form protoporphyrinogen IX in the cell nucleus. PpIX is synthesized from protoporphyrinogen IX via protoporphyrinogen oxidase activity, and heme is synthesized via the uptake of iron into the tetrapyrrole structure by ferrochelatase in the mitochondrial membrane ( Fig.

5-aminolevulinic acid-induced fluorescence in cerebellar primary central nervous system lymphoma: a case report and literature review

“…Almost all cases were positive (strong and vague) for 5-ALA-induced fluorescence. However, one study reported that 20% of PCNSL cases lacked 5-ALA-induced fluorescence (12). In the present case, we chose an open resective approach to the cerebellar tumor, without exposing the fourth ventricle, and observed strong 5-ALA-induced fluorescence of the tumor that was histologically compatible with DLBCL.…”

“…Recently, 5-ALA has also been identified as a promising intraoperative marker in stereotaxic biopsies for malignant gliomas (5,15). However, clinical application of 5-ALA in primary central nervous system lymphoma (PCNSL) is currently uncommon (2, 8,12).…”

Preoperative Prediction of Whether Intraoperative Fluorescence of Protoporphyrin IX Can Be Achieved by 5-Aminolevulinic Acid Administration

“…When 5-ALA is administered, the tumor cells take it up and synthesize heme actively. However, ferrochelatase, which is necessary for synthesis of heme from PPIX in the tumor cells, is relatively insufficient, and PPIX accumulates in tumor cells because, as a result, synthesis does not advance [3,6]. This PPIX may be found in surrounding tissues where no tumor cells exist [7].…”

“…However, PPIX fluorescence is not observed in all tumors when 5-ALA is administered [3,4]. There is no method of ascertaining preoperatively whether PPIX fluorescence of the tumor tissue will be observed until exposure to an excitation light of the ultraviolet region during tumor resection.…”

“…Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection using 5-aminolevulinic acid (5-ALA) is among the most useful tools for determining the removal area for infiltrating tumors like gliomas [1][2][3][4]. However, PPIX fluorescence is not observed in all tumors when 5-ALA is administered [3,4].…”