Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron Oxide Nanoparticle Clusters
Jayesh P Thawani1,2, Ahmad Amirshaghaghi2, Lesan Yan2
1Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Abstract:
A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real-time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles-with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20-30% of the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery demonstrate increased progression-free survival compared to animals undergoing microscopic surgery.
Insights
This study introduces a novel dual-contrast agent for brain tumor surgery, improving detection and resection. Photoacoustic-guided surgery using this agent significantly enhanced progression-free survival in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Medical Imaging
Background:
- Incomplete surgical resection is a primary cause of local tumor recurrence in brain tumor surgery.
- Current adjunctive technologies and contrast agents have limitations in real-time intraoperative use.
- There is a need for effective contrast agents that can be used preoperatively and intraoperatively.
Purpose of the Study:
- To develop and evaluate a novel, dual-modality contrast agent for improved brain tumor detection and resection.
- To assess the efficacy of magnetic resonance (MR) and photoacoustic (PA) imaging for tumor delineation.
- To investigate the potential of this agent in enhancing surgical outcomes.
Main Methods:
- Formulation of a novel contrast agent using FDA-approved indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles.
- Characterization of ICG-SPIO cluster stability, encapsulation efficiency, and ICG payload.
- Evaluation of tumor uptake via enhanced permeability and retention (EPR) effect.
- Preclinical testing in a mouse model using MR and PA imaging, comparing PA-guided surgery to microscopic surgery.
Main Results:
- ICG-SPIO clusters demonstrated ≈100% encapsulation efficiency and high ICG payload (20-30%).
- The clusters were stable under physiologic conditions and showed tumor uptake via EPR.
- MR imaging confirmed detectability of the ICG-SPIO clusters.
- Animals undergoing PA-guided surgery showed significantly increased progression-free survival compared to microscopic surgery controls.
Conclusions:
- The novel ICG-SPIO contrast agent enables dual-mode preoperative (MR) and intraoperative (PA) imaging.
- This agent is stable, tumor-avid, and enhances surgical guidance.
- PA-guided surgery using ICG-SPIO clusters improves outcomes in a preclinical brain tumor model, offering a promising adjunctive technology.
