Lmap-09 recapitulating laser interstitial thermal therapy in preclinical brain tumor models

Abstract Laser interstitial thermal therapy (LITT) is a minimally-invasive option for cytoreduction of recurrent or otherwise difficult-to-access intracranial tumors. Relative to resection, ablated tumor tissue remains in situ, facilitating recognition of tumor antigens and a targetable immune response. To investigate the immune consequences of LITT, we developed a model of stereotactic laser ablation for use with existing syngeneic glioma and intracranial metastasis cell lines. A 1064 nm diode-based Nd:YAG laser (Monteris Medical) was used to thermally ablate normal brain tissue or CT-2A tumors in C57BL6/J mice. Ablations were performed at 10 days post-implantation at + 2 ML, + 1 AP, -3 DV using a stereotactic frame. Simultaneous temperature measurements were taken using a thermocouple probe implanted to the same depth 2 mm posterior. We first used serial T2-weighted MRI imaging to accurately track the tumor growth characteristics and identify a safe lesion size for ablation, selecting 10 days post-implantation for subsequent experiments and 2 mm posterior as the ideal position to monitor temperature at the lesion edge. To assess the thermal characteristics of our laser, we ablated mouse brains at 1 W and 2 W for 30, 60, or 90 seconds each, finding that 1 W for 90 seconds produced an ablation that did not char or coagulate tissue outside the ablation zone and recapitulated human ablation findings on H&E staining 24h post-LITT. We next implanted CT-2A tumors for ablation with the selected dose, following mice for survival between the LITT and sham-ablated groups. A subset of mice were imaged using T2-MRI at 1, 3, 7, and 14 days post-surgery. Our model recapitulates the essential clinicopathological findings of LITT and is well suited apply to a variety of intracranial tumor models and LITT-adjunctive therapies.