EXTH-30. GOLD NANOSTARS OBVIATE LIMITATIONS TO LASER INTERSTITIAL THERMAL THERAPY (LITT) AND ENHANCE THE POST-LITT IMMUNE RESPONSE

Abstract

Abstract Laser interstitial thermal therapy (LITT) is a minimally-invasive technique for the treatment of intracranial tumors that uses a stereotactically-guided laser and real-time magnetic resonance imaging (MRI) to monitor ablation progress. Previous applications of gold nanostars (GNS) in laser ablation of tumors have studied extracranial tumors only and utilized externally administered near infrared radiation that cannot penetrate the cranial compartment. Herein, we present a novel platform for employing GNS in intracranial tumors. We developed non-toxic GNS that exhibit maximum photothermal effects at the 1064 nm laser wavelength used in the FDA-approved clinical Neuroblate® LITT system. Monte Carlo simulations demonstrate that our GNS can accelerate and focus thermal energy distributions. Using ex vivo tumor phantom models, we found that GNS-infused phantoms demonstrate more rapid heating and improved spatial conformation of thermal energy, with neighboring material exposed to lower temperatures than controls. In our intracranial CT-2A glioma model, we quantified accumulation of radiolabeled GNS in tumor tissue via PET/CT. As further validation of tumor-selective GNS accumulation, we used two-photon luminescence to show that GNS selectively accumulate and are retained in intracranial tumors at 24 and 72 hours post-injection. We then utilized our in vivo heterotopic CT-2A model to assess the capacity of systemically-delivered GNS to augment laser ablation; we were able to achieve higher ablation temperatures and more efficient temperature ramping with LITT+GNS. Finally, we explored the potential of LITT+GNS to synergize with immunotherapy to further enhance the post-ablation immune response and found that combination therapy resulted in improved tumor control and immunologic memory that was protective against tumor rechallenge. These results support the ability of GNS to optimize LITT for the treatment of intracranial tumors by improving efficiency and safety, and illustrate the potential of this platform to synergize with immunotherapy.