Evidence map›Paper›PMID 40163716›Full record

ArticleNeuro-oncology2025

The impact of therapeutic radiation on drug distribution across the blood-brain barrier in normal mouse brain and orthotopic glioblastoma tumors.

Wenjuan Zhang, Michael P Grams, Rajneet K Oberoi, Ju-Hee Oh, Paul A Decker, Terence T Sio, Surabhi Talele, Zachary C Wilson, Margaret A Connors, Katrina K Bakken and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Wenjuan ZhangBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Michael P GramsDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Rajneet K OberoiBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Ju-Hee OhBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Paul A DeckerDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-3756-4227
Terence T SioBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Surabhi TaleleBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Zachary C WilsonDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Margaret A ConnorsDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Katrina K BakkenDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Brett L CarlsonDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Lauren L OttDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Danielle M BurgenskeDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Erik J TryggestadDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Jeanette E Eckel PassowDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
William F ElmquistBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0001-7489-4885

Funding

Therapy Evaluation CoreU19CA264362 · NCI · MAYO CLINIC ROCHESTER · PI PARNEY, IAN F · 2021 to 2025
$7.6M
Pre-Clinical Novel Radiosensitizer Evaluation Program for Brain TumorsU01CA227954 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2018 to 2022
$3.0M
National Brain Tumor Society 21-004061National Brain Tumor Society AWD0006946NCI NIH HHS U01 CA227954NCI NIH HHS U19 CA264362NIH HHS U01CA227954NIH HHS U19CA264362
6 · The paper itself

Abstract

backgroundMost oncology therapeutics have limited distribution into the brain, and developing strategies to overcome this limitation would be clinically impactful. While therapeutic radiation is often cited as a strategy to accomplish this, there are no published studies demonstrating the effect of radiation on drug distribution into the brain or brain tumors.

methodsMice were treated with brain radiation (6 Gy × 5, 4 Gy × 10; 40 Gy × 1) and dosed with drugs (levetiracetam, cefazolin, nedisertib, brigimadlin, apitolisib, or GNE-317) at times ranging from just prior to months after radiation. Plasma and tissue drug concentrations were measured by LC-MS/MS.

resultsRadiation did not significantly enhance drug delivery into brain tissue for levetiracetam, cefazolin, GNE-317, apitolisib, or nedisertib at any time post-radiation. Even a single, supra-therapeutic dose of radiation (40 Gy) did not significantly affect brain distribution of GNE-317 or apitolisib (P ≥ .07) from 16 to 160 hours post-radiation. For brigimadlin, radiation (6 Gy × 5) was associated with a modest but significant increase in drug accumulation only at 72 hours post-radiation (brain-to-plasma ratio 0.014 ± 0.006 vs. 0.025 ± 0.010, respectively; P = .04), but not at any other timepoint (24 hours, 15, 28, 94, 133, 183 days; P > .05). Similarly, radiation (6 Gy × 5) of orthotopic tumors did not increase levels of brigimadlin in GBM10 or GBM108 or nedisertib in GBM108 (P > .05).

conclusionsRadiation had no meaningful impact on drug delivery into brain or brain tumors for the drugs tested.

Indexed as

Antineoplastic AgentsBlood-Brain BarrierBrainBrain NeoplasmsGlioblastomaAnimalsFemaleHumansMiceTissue DistributionAntineoplastic AgentsBBB permeabilitybrain tumor modelsdrug deliveryradiation therapy

Identifiers

PMID40163716
PMCPMC12403047

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.