Clinically useful tumor fluorescence greater than 24 hours after 5-aminolevulinic acid administration

Abstract

Background: 5-aminolevulinic acid (5-ALA) is a valuable surgical adjuvant used for the resection of glioblastoma multiforme (GBM). Since Food and Drug Administration approval in 2017, 5-ALA has been used in over 37,000 cases. The current recommendation for peak efficacy and intraoperative fluorescence is within 4 h after administration. This narrow time window imposes a perioperative time constraint which may complicate or preclude the use of 5-ALA in GBM surgery.

Case description: This case report describes the prolonged activity of 5-ALA in a 66-year-old patient with a newly diagnosed GBM lesion within the left supramarginal gyrus. An awake craniotomy with language and sensorimotor mapping was planned along with 5-ALA fluorescence guidance. Shortly, after receiving the preoperative 5-ALA dose, the patient developed a fever. Surgery was postponed for an infectious disease workup which proved negative. The patient was taken to surgery the following day, 36 h after 5-ALA administration. Despite the delay, intraoperative fluorescence within the tumor remained and was sufficient to guide resection. Postoperative imaging confirmed a gross total resection of the tumor.

Conclusion: The use of 5-ALA as an intraoperative adjuvant may still be effective for patients beyond the recommended 4-h window after initial administration. Reconsideration of current use of 5-ALA is warranted.

Keywords: 5-ALA; 5-Aminolevulinic acid; GBM; Glioblastoma multiforme.

Figure 1:

Preoperative magnetic resonance imaging (MRI) of the brain with and without contrast demonstrating contrast-enhancing left parietal cystic lesion. (a) Axial MRI T1-weighted, (b) axial T1-weighted with gadolinium, (c) sagittal T1-weighted with gadolinium, and (d) coronal T1-weighted with gadolinium.

Figure 2:

Intraoperative view of fluorescent, pathologic tissue visualized through a small corticotomy window. Photo taken at the onset of the resective portion of the surgery, approximately 33 h after administration of 5-aminolevulinic acid. Normal brain parenchyma did not fluoresce and all pathologic specimens that fluoresced were positive for tumor.

Figure 3:

Intraoperative navigation depicting location of biopsy sample and visualized fluorescence under blue-light illumination in the (a) coronal plane, (b) sagittal plane, (c) axial plane, and (d) microscope luminescence control window. The time stamp indicates approximately 32 h after initial administration of 5-aminolevulinic acid. The blue lines in (a), (b), and (c) indicate location of fluorescent biopsy sample depicted in (d).

Figure 4:

Postoperative T1-weighted (a and c) pre-contrast and (b and d) post-contrast magnetic resonance imaging demonstrating complete removal of the contrast-enhancing tumor.