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<p>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&#xa0;days post-treatment. Immunofluorescence (IF) staining characterized immune cell activation. The distribution of doxorubicin released from intravenously administered Thermodox<sup>®</sup> was also evaluated. LITT disrupted the BBB, enabling Evans Blue dye and doxorubicin penetration up to 4&#xa0;mm from the probe. Tumor burden was reduced by LITT, as shown by decreased hypercellularity on H&amp;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<sup>®</sup>-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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年1月15日

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  • Prazwal Athukuri,
  • Karina Moreno,
  • Malcolm F. McDonald,
  • Ashley Puentes,
  • Alfred Dei-Ampeh,
  • Anantha Marisetty,
  • Yuhui Yang,
  • Sungho Lee,
  • Khatri Latha,
  • David Needham,
  • Ganesh Rao

摘要

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.

Graphical Abstract