Abstract
INTRODUCTION: Laser Interstitial Thermal Therapy (LITT) is an emerging clinical option for the thermal ablation of intracranial lesions. Current limitations for LITT, however, include the diameter of ablation (< 3cm per trajectory) and lack of inherent specificity for tumor margins. Gold nanoparticles act as “lightning rods” to expand laser treatment coverages. Here, we employ plasmon-activated gold nanostars (GNS) with selective tumor uptake to increase LITT coverage area and tumor specificity in a murine model, and also demonstrate their ability to expand coverage in a clinically-relevant sized model using brain phantoms. METHODS: CT2A murine glioma cells were implanted into the right cerebral hemisphere. GNS were administered intravenously. Selective GNS uptake in tumors was demonstrated by micro-PET-CT. Microlaser fibers (700um) were used to deliver laser light to tumors. Brain phantoms were composed of agarose gel with embedded 5x5x5 cm(3) agarose “tumors” with or without interspersed GNS. A diffuse-tip probe was used to deliver laser light to phantom tumors in the intraoperative MRI suite. MRI thermometry measured temperature change in phantoms. RESULTS: Systemically administered GNS were selectively taken up by tumor compared to surrounding brain. Murine gliomas treated with GNS + laser showed an expanded tumor-conforming zone of cytotoxic edema on small animal MRI compared to tumors treated with laser alone. In phantoms containing GNS, the kill zone (43°C for 10 min) extended to 3.8cm in diameter, compared to 2.0cm in phantoms without GNS. Additionally, the phantoms containing GNS heated faster, reached higher temperatures, and displayed a more homogeneous zone of treatment. CONCLUSION: We demonstrate the capacity to use nanotechnology to overcome the size and specificity limitations for LITT, both in an in vivo murine intracranial glioma model, as well as in a more relevantly sized brain phantom model. Clinical trials in canine glioma are planned to enable an IDE application.