Biom-106. Microperfusion-Based Biomarker Analysis in Glioblastoma: Integrating Preclinical and Clinical Perspectives

Glioblastomas (GBMs) are aggressive brain tumors that pose therapeutic challenges. Microperfusion (MP) probes offer a unique method for real-time sampling of extracellular biomarkers and drug responses within the tumor microenvironment. Compared to microdialysis probes, MP probes can sample large molecules without a molecular weight cut-off, making them particularly valuable for drug quantification and novel biomarker detection. In this study, MP was used to measure the GDF-15 (24.8 kDa) levels in TP53 wild-type, MDM2-amplified GBM treated with Brigimadlin, using orthotopic mouse models. Patient-derived xenograft (GBM108) was implanted intracranially in mice, and tumor growth was monitored by bioluminescent imaging or MRI. A single MP probe was placed in the tumor for the Brigimadlin group and compared with the vehicle group. MP samples were collected over four-hour daily sessions across a baseline day and three treatment days. Brigimadlin treatment led to an increase in GDF-15 within the tumor catheter during treatment days (mean: 225.3 pg), compared to stable levels in the vehicle control group (mean: 66.4 pg), consistent with activation of the p53 pathway. In a separate study of blood–brain barrier (BBB) permeability, FITC-Dextran analysis revealed a decline in BBB permeability from 0.4 μg/mL at 24 hours post-implantation to a stable 0.02 μg/mL by 72 hours, reflecting sustained but reduced permeability. MP enabled quantification of GDF-15 dynamics in vivo, highlighting its potential in clinical settings. An investigational device exemption has been secured for an upcoming clinical trial deploying intraoperative use of cerebral microperfusion catheters.