Agents for Fluorescence-Guided Glioblastoma Surgery

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression and a median survival of no more than 12-18 months. Fluorescence-guided surgery is crucial, as it allows for tumor visualization and aids in its complete removal, which is essential for improving survival rates. We conducted a literature review to identify fluorescent agents that have been utilized in the removal of GBM and to assess their benefits in achieving maximum tumor resection. Our analysis focuses on their advantages, limitations, and potential impact on improving surgical precision and patient outcomes. We searched the PubMed database for studies published on fluorescence-guided resection of GBM and evaluated the utility of each agent in terms of outcomes, gross total resection (GTR), and their sensitivity and specificity for the tumor. The literature review revealed that the three agents successfully utilized are 5-aminolevulinic acid (5-ALA), sodium fluorescein, and indocyanine green. In addition to these, a variety of dyes have been investigated in studies, including peptides, lipids, and nanosystems, which appear to be very promising. To date, numerous fluorescent agents have been proposed for the surgical resection of GBM. However, 5-aminolevulinic acid (5-ALA) remains the only agent widely adopted in clinical practice, as its safety and efficacy have been well-established. Further clinical trials and studies are necessary to assess the utility, effectiveness, and potential advantages of emerging fluorescent dyes in enhancing GBM resection and improving patient outcomes.

Keywords: 5-ALA; fluorescein; fluorescence dyes; fluorophores; glioblastoma; indocyanine green; luminescent agents.

Figure 1

Structure of fluorescence-guided resection fluorescent agents. This figure also shows how 5-aminolevulinic acid is metabolized into protoporphyrin IX, the fluorescent dye, and how light exposure generates reactive oxygen species (ROS) during photodynamic therapy.

Figure 2

Structure of tozuleristide (BlZ-100). This tumor-targeting agent is derived from chlorotoxin, a component found in scorpion venom, and a fluorescent dye.

Figure 3

Structure of two commonly used alkylphosphocholine analogs. Both are based on the CLR1404 backbone, with the addition of a fluorescent analog in CLR1501 and a near-infrared analog in CLR150.