A novel murine model of LITT for glioblastoma reveals tumor reduction, BBB permeabilization, and drug delivery via ThermoDox^®.

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for brain tumors that are recurrent or surgically inaccessible. We developed a murine model of LITT to investigate its effects on tumor burden, immune activation, and delivery of heat-activated therapeutics. We engineered a preclinical LITT system using a 1064-nm laser coupled to a 400-μm fiber-optic probe. Orthotopic gliomas were established in the right frontal cortex of BL6 mice using luciferase-transduced glioma cells. Ten days post-implantation, mice were treated with LITT (0.45 or 0.75 W). Tumor response and blood-brain barrier (BBB) disruption were assessed using bioluminescence imaging (BLI), Evans Blue dye, and histology at 3, 7, and 14 days post-treatment. Immunofluorescence (IF) staining characterized immune cell activation. The distribution of doxorubicin released from intravenously administered Thermodox^® was also evaluated. LITT disrupted the BBB, enabling Evans Blue dye and doxorubicin penetration up to 4 mm from the probe. Tumor burden was reduced by LITT, as shown by decreased hypercellularity on H&E and reduced BLI signal, while sham-treated mice showed tumor progression. A reproducible ablation zone formed at the probe site. IF revealed increased IBA1 + macrophages and T cell infiltration in LITT-treated brains. Thermodox^®-derived doxorubicin distribution correlated with thermal diffusion and matched a Fickian perfusion model. We present a reproducible preclinical model of LITT that enables investigation of tumor ablation, immune modulation, and thermally triggered drug delivery. These findings support the use of LITT as a platform for combinatorial strategies in glioma treatment.

Duke Scholars

Author David Needham Thomas Lord Department of Mechanical Engineering and Materia ...