Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium

Abstract

The authors have recently performed a fluorescence-guided tumor resection procedure by using high-dose fluorescein sodium without any special surgical microscopes for the intraoperative visualization of glioblastoma multiforme (GBM), and they report on the actual procedure and clinicopathological findings. Thirty-two patients with GBMs underwent tumor resection during which this fluorescence-guided procedure was used. Fluorescein sodium (20 mg/kg) was intravenously injected after dural opening at the craniotomy site. The tumor was stained almost homogeneously yellow and the color was intense enough to be readily perceived for resection. The center of the solid lesion was stained a deep yellow and surrounded by a transition zone that was faintly stained. The colored lesion was clearly distinguishable from the unstained zone outside the GBM, particularly in the white matter. Both the deeply and faintly stained regions included endothelial proliferation and dense tumor cells. In the unstained region, less dense tumor cells were consistently revealed; however, no endothelial proliferation could be seen. Gross-total resection (GTR) was successful in 84.4% of the patients who received an injection of fluorescein sodium, which accounted for 100% of those in whom all the visible yellow color (both the deeply and faintly stained regions) was judged to have been resected during operation. Gross-total resection was performed in 100% of the patients who underwent the fluorescence-guided procedure and assigned to Stage I, a GBM stage in which, as a therapeutic policy, the tumor should be resected as radically as possible. The GTR rates in patients who received fluorescein sodium were significantly higher than those in patients who did not (73 patients with GBMs who underwent tumor resection without the fluorescence-guided procedure). Although the extent of surgery was revealed to be one of the significant and independent prognostic factors for GBM, the fluorescein sodium-guided resection procedure was not a significant or independent prognostic factor in this series. This surgical procedure does not require any special surgical microscopic equipment and is simple, safe, useful, readily accomplished, and universally available for resection of GBMs. Its efficacy simplifies the surgical procedure of navigating the stained lesion from the unstained area to achieve GTR of GBMs, which can be demonstrated on magnetic resonance images.

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

“…16,19,24 Fluorescein (MW 376 D) is an organic fluorescent dye with peak excitation at 490 nm and emission between 500 and 550 nm, dependent on pH and the ionic strength of the solution. 25 This dye can be safely administered intravenously in humans and has been used clinically in multiple applications.…”

A Novel High-resolution <em>In vivo</em> Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

“…It is also feasible to look at kinetics of the drug due to the promise of single-cell resolution. Fluorescein (GFP+) is used to delineate tumors during surgery to ensure maximal resection is achieved 26 . By injecting intravenously whilst imaging it is possible to demonstrate that the delineation occurs NOT through the active uptake of the Fluorescein into the tumor cells themselves, but instead through the collection of the drug into the stromal area with time, seen by the lack of co-localization 10 min following the injection of the Fluorescein (Figure 4D).…”

“…By using RFP+ BM we are able to study the role VEGF has on the recruitment of BMDCs to the vasculature. Most recently we have utilized the model to study drug kinetics looking at the mechanism behind the tumor-delineating drug Fluorescein 26 , at a cellular level. Through the use of a custom-built in house small animal irradiator we have been able to integrate stereotactic delivered radiation to assess the response of both tumor and BMDCs to treatment.…”

Surgical strategy in case with co-existence of malignant oligodendroglioma and arteriovenous malformation: A case report

“…After hemostasis was achieved and a dural incision was made, both lesions were exposed on the surface of the right frontal lobe (Figure 2(A)). We administered fluorescein sodium to discriminate the tumor from the normal brain tissue by the previously reported method [2]. The tumor stained deep yellow and was sharply circumscribed.…”