Novel IDH1-Targeting Fluorescent Probe Enables Intraoperative Visualization and Resection of Glioblastoma

Area of Science:

• Biomedical Engineering
• Oncology
• Molecular Imaging

Background:

• Glioblastoma (GBM) is an aggressive brain tumor where complete surgical resection is crucial for patient survival.
• Current fluorescence-guided surgery methods face limitations due to glioblastoma heterogeneity.
• Targeting specific molecular markers is essential for accurate intraoperative navigation.

Purpose of the Study:

• To develop and evaluate a novel fluorescent probe, QM-SO3H, for intraoperative glioblastoma navigation.
• To assess the probe's ability to target the wild-type IDH1 enzyme.
• To demonstrate the probe's efficacy in delineating tumor boundaries and guiding surgical resection.

Main Methods:

• Design of QM-SO3H using a sulfonated quinoline-malononitrile framework with aggregation-induced emission (AIE) characteristics.
• Evaluation of the probe's fluorescence response and specificity to the IDH1 enzyme in vitro.
• Testing the probe's performance in an orthotopic U87Luc GBM xenograft model, assessing blood-brain barrier penetration and tumor visualization.

Main Results:

• QM-SO3H demonstrated a highly selective "turn-on" fluorescence response upon binding to the IDH1 enzyme.
• The probe successfully penetrated the tumor blood-brain barrier and specifically illuminated GBM xenografts.
• QM-SO3H clearly delineated tumor margins, guided complete resection, and detected microtumors (<1 mm).

Conclusions:

• QM-SO3H represents a novel imaging strategy for glioblastoma by targeting the IDH1 enzyme.
• This probe offers a promising alternative for fluorescence-guided tumor resection in GBM patients with high IDH1 expression.
• QM-SO3H can also be utilized for studying IDH1-related pathophysiology.