ABS 020: Combining Laser Interstitial Thermotherapy with High-Throughput Screening-Identified Drugs for Malignant Brain Tumor Treatment

Ziqi Cui ¹, Anjali Chauhan ¹, Grace Hey ², Nesrine Benslimane ³ , Michael Cameron ³ , Virneliz Fernandez Vega ³ , Nagheme Thomas ¹, Ravi Kumar ¹, Neel N. Patel ¹, Macaulay Tomdio ¹, Niccolò A. Rugger ¹, Marianne Kozuch ⁴, Siva Rama Raju Kanumuri ⁵, Frank Bova ¹, Timothy Spicer ³ , Maryam Rahman ¹ ²

¹ Lillian S. Wells Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL
² University of Florida College of Medicine, Gainesville, FL
³ Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, University of Florida, Gainesville, FL
⁴ Center for Environmental & Human Toxicology, Analytical Toxicology Core Lab, Gainesville, FL
⁵ Department of Pharmaceutics and CTSI-Translational Drug Development Core, University of Florida, Gainesville, FL

The Van Wickle Journal (2026) Volume 2, ABS020

Introduction: Malignant brain tumors are difficult to treat due to their resistance to conventional therapies and the restricted permeability of the blood–brain barrier (BBB) which limits the effectiveness of drug delivery to the brain. Laser interstitial thermotherapy (LITT) treatment of brain tumors is directly cytotoxic and also opens the BBB, enabling the delivery of drugs that otherwise do not cross it. High-throughput screening (HTS) complements this approach by identifying patient-specific therapeutic candidates. The purpose of this study was to evaluate the feasibility of using LITT to increase drug delivery to brain tumors in murine models.

In the care of individuals with multiple sclerosis (MS), treatment of depression represents a vexing problem. Depression is common in people with MS and contributes to worsening MS disability, yet it tends to be under-ascertained in clinical practice, emphasizing the need for novel diagnostic approaches. Many discrete measures can be extracted from EHRs to indicate a patient’s mental health, such as ICD-9 codes for depression or prescriptions for antidepressants; however, these measures may be incomplete or unavailable across healthcare systems.

Methods: Experiments were performed with syngeneic murine glioma model (KR158-Luc) in C57BL/6 mice and in patient derived xenograft (PDX) model using human melanoma brain metastasis tumor in NSG mice. LITT was delivered via intracranial implantation of the laser probe and temperature probe (Frain et al. Neurosurg Focus 2024). HTS was performed with a 179-drug panel using the melanoma brain metastasis tumor.

Results: We found that intratumoral levels of both TMZ and carboplatin increased following LITT treatment in mice bearing intracranial KR158-luc tumors. When combined with LITT, intratumoral carboplatin increased significantly compared to carboplatin alone (1252 vs. 352 ng/g; p = 0.0054) as measured by ICP-MS. The combination also significantly improved survival. In the PDX melanoma brain metastasis model, plasma levels of carfilzomib were lower with LITT than with carfilzomib alone, indicating a higher level of brain penetration. However, concentration of carfilzomib could not be detected by LC-MS in the brain, as it was rapidly degraded, and thus did not show a survival benefit. Survival study showed LITT with romidepsin significantly extended survival versus untreated controls.

Discussion: The prompt was highly sensitive to neurologist documentation of depression in clinical notes; it inferred both present/treated depression from other note components. Potential applications include quality improvement initiatives aiming to improve depression care on a cohort level.