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

Abstract

Protoporphyrin IX (PPIX) fluorescence-guided brain tumor resection, using 5-aminolevulinic acid (5-ALA), is among the most valuable tools for determining tumor removal area. However, PPIX fluorescence is not necessarily achieved during an operation visually even when 5-ALA is used, and we do not know until tumor exposure to the excitation light of the ultraviolet region whether PPIX fluorescence has been achieved. When a particular biopsy and frozen section diagnosis is made, the reason for lack of PPIX fluorescence in the tissue cannot be judged. We do not know whether the tumor fails to fluoresce or no fluorescence is seen because it is not the main body of the tumor. We investigated whether the presence or absence of tumor fluorescence could be predicted by examining urinary porphyrin before surgery, at the time of intraoperative fluorescence diagnosis using 5-ALA. The urine of brain tumor patients 2 hours after 5-ALA administration was irradiated with a 405 ± 1 nm laser light. The patients were divided into a fluorescent urine group and negative fluorescent urine group. Red fluorescence was observed in response to the 405 ± 1 nm laser beam for all tumors in the fluorescent urine group. Clear red fluorescence was not observed even with 405 ± 1 nm laser beam irradiation in any tumors in the negative fluorescent urine group. Preoperative prediction of the intraoperative fluorescence of PPIX can be achieved by observation of urine 2 hours after 5-ALA administration with exposure to a 405 ± 1 nm laser light.

Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas

“…The intraoperative fluorescence effect is dependent on the conversion of 5-ALA to fluorescent Protoporphyrin IX and is therefore likely facilitated by enzymes of the heme biosynthesis pathway and may also be impacted by the eventual enzymatic breakdown of heme [32,33]. In addition to the locally increased concentration of heme biosynthesis metabolites in glioma tissue, higher urine and plasma concentrations of PpIX have been identified in patients with fluorescent gliomas compared to those that showed no or only minimal fluorescence [34,35]. Since high-grade gliomas (WHO grades III and IV) usually demonstrate visible 5-ALA fluorescence and such fluorescence is frequently absent in low-grade gliomas (WHO grade II) as well as 5-ALA is metabolized via the heme biosynthesis pathway, we assume that 5-ALA fluorescence might be a reliable intraoperative indicator for the heme biosynthesis mRNA signature [28,[36][37][38].…”

Quantification of Protoporphyrin IX Accumulation in Glioblastoma Cells: A New Technique

“…The presence of PpIX fluorescence within the tumor bed allows for discrimination between neoplastic and nonneoplastic cells [ 4 ]. Yet, not all brain tumors accumulate sufficient quantities of PpIX to make the use of 5-ALA advantageous during surgery [ 5 , 6 ], and it is not fully understood how 5-ALA might affect other physiological processes. At this time, it is unknown if prescribed medications of tumor patients or if drugs given to patients just prior to/during surgery interfere with 5-ALA synthesis and/or PpIX accumulation.…”