Related Experiment Video
Updated: Sep 13, 2025
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
A micellar nanoprobe for fluorescence image-guided delineation of glioblastoma margins
M Ali1, K T H van der Kuil2, P Khodakivskyi3
1Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, Rotterdam 3015 GD, the Netherlands; Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, Rotterdam 3015 GD, the Netherlands; Department of Neurosurgery, Erasmus MC Cancer Institute, Brain Tumor Center, Erasmus University Medical Center, Dr. Molewaterplein 40, Rotterdam 3015 GD, the Netherlands.
Abstract:
Despite remarkable advancements in (neuro)-oncology, glioblastoma (GBM) remains the most aggressive primary brain tumor with a dismal overall survival of 14-17 months. A critical factor contributing to its poor prognosis is the high local recurrence rate, observed in 80-90 % of patients. This is largely due to the tumor's highly infiltrative growth pattern, which renders complete surgical resection impossible. Although surgery remains a cornerstone of initial treatment, current surgical techniques lack the precision to reliably detect and remove infiltrative margins. Recent state-of-the-art trials have proposed more aggressive surgical strategies aiming to reduce residual disease and mitigating local recurrence. However, implementing such extensive resections requires intraoperative imaging tools with enhanced, real-time sensitivity-capabilities that current technologies lack. Here, we report the preclinical validation of a near-infrared (NIR), fatty acid-based probe formulated in micelles (mFA-ICG) for image-guided surgery of GBM. This includes a comprehensive characterization of its pharmacokinetics, biodistribution, and toxicity profile. Notably, the micellar formulation demonstrated high stability, extended half-life, deep tissue penetration, improved targeting, enhanced fluorescence signal (compared to clinical standards), and a favorable safety profile in relevant models. We further validated the efficacy of mFA-ICG in orthotopic patient-derived, transgenic and organotypic patient' tissue slice models of GBM where our data confirm both in- and ex vivo specificity of NIR signal. Collectively, these findings support the safety and translational potential of mFA-ICG and suggest it may significantly improve delineation at the infiltrative edge. These advantages position mFA-ICG as a promising candidate for a trial in GBM patients.
Insights
A new near-infrared, fatty acid-based probe (mFA-ICG) shows promise for improving glioblastoma (GBM) surgery by enhancing tumor margin visualization, potentially reducing recurrence rates in patients.
Area of Science:
- Neuro-oncology
- Medical Imaging
- Biomedical Engineering
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with high recurrence rates (80-90%) due to infiltrative growth, making complete surgical resection challenging.
- Current surgical techniques and imaging lack the precision to detect and remove all tumor margins, contributing to poor patient prognosis and limited survival (14-17 months).
Purpose of the Study:
- To preclinically validate a novel near-infrared (NIR) fatty acid-based probe formulated in micelles (mFA-ICG) for enhanced image-guided glioblastoma surgery.
- To characterize the probe's pharmacokinetics, biodistribution, toxicity, and efficacy in preclinical models to assess its translational potential.
Main Methods:
- Development and characterization of a micellar fatty acid-ICG formulation (mFA-ICG).
- Assessment of mFA-ICG pharmacokinetics, biodistribution, and safety profile in relevant preclinical models.
- Validation of mFA-ICG efficacy using orthotopic patient-derived, transgenic, and organotypic GBM tissue slice models for in vivo and ex vivo NIR signal specificity.
Main Results:
- The mFA-ICG formulation exhibited high stability, an extended half-life, deep tissue penetration, and improved targeting compared to clinical standards.
- The probe demonstrated enhanced fluorescence signal and a favorable safety profile in preclinical models.
- In vitro and ex vivo studies confirmed the specificity of the NIR signal in various GBM models, highlighting its potential for delineating infiltrative tumor margins.
Conclusions:
- The preclinical validation supports the safety and translational potential of mFA-ICG for image-guided glioblastoma surgery.
- mFA-ICG may significantly improve the delineation of infiltrative tumor margins, offering a promising tool for future clinical trials in GBM patients.
- Enhanced visualization of tumor margins could lead to more aggressive surgical strategies, reduced residual disease, and potentially improved patient outcomes.
More Related Videos
09:09Laser Capture Microdissection of Glioma Subregions for Spatial and Molecular Characterization of Intratumoral Heterogeneity, Oncostreams, and Invasion
Published on: April 12, 2020
09:17Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022