ArticleNeuro-oncology2026
Window of opportunity evaluation of blood-brain barrier permeability heterogeneity within and across high-grade glioma patients.
Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Impact of MRI modality selection on glioma sub-region segmentation using 3D U-Net and Attention U-Net: A comparative evaluation across ten MRI sequences.European journal of radiology open · 2026Article
- Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response.Nature reviews. Cancer · 2026Review
- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- The value of target-site physiologically-based pharmacokinetics for high-affinity small molecules: a mechanistic foundation for precision dosing in oncology and hematology.Cancer chemotherapy and pharmacology · 2026Article
- Evaluating "brain permeability": A critical issue for the development of therapeutic agents for primary and metastatic brain tumors.Neuro-oncology · 2026Review
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
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Authors and funding
26 authors.
Funding
Abstract
backgroundDisruption of the blood-brain barrier (BBB) in high-grade brain tumors is characterized by contrast accumulation on diagnostic imaging. This window of opportunity study correlates contrast imaging features with the tumor distribution of BBB-permeable (levetiracetam) and -impermeable (cefazolin) drugs.
methodsPatients with a clinical diagnosis of a high-grade brain tumor underwent MRI for surgical planning. Cefazolin and levetiracetam were administered prior to skin incision, and serial plasma and image-registered tumor samples were collected during the operation. Drug levels were measured by LC-MS/MS, tissue drug levels were corrected for residual blood, and tumor-to-plasma concentration ratios were calculated. Intraoperative microdialysis was performed in a subset of patients to measure the same two drugs.
resultsTumor (n = 125) and plasma (n = 261) samples were available for analysis from 42 operative cases. Across all samples, the tumor-to-plasma ratio was significantly lower for cefazolin (marginal mean [MM]: 0.15, 95% CI: 0.11-0.19) as compared to levetiracetam (MM: 0.70, 95% CI: 0.64-0.75; P < .001). When compared between contrast-enhancing and non-enhancing regions, tumor-to-plasma ratios for cefazolin varied by 4.4-fold (0.27, 95% CI: 0.20-0.35 vs. 0.06, 95% CI: 0.04-0.08, respectively; P < .001), and varied for levetiracetam by 1.4-fold (0.88, 95% CI: 0.78-0.97 vs. 0.61, 95% CI: 0.55-0.66, respectively; P < .001). These results were confirmed with the intra-operative microdialysis and a population pharmacokinetic analysis.
conclusionsThis study demonstrates significant inter- and intra-tumoral heterogeneity in drug delivery for both levetiracetam and cefazolin within high-grade brain tumors that is not necessarily predicted by clinical MR imaging and may reflect tumor-induced changes in both perfusion and BBB integrity.
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