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

IF 16.4 1区医学 Q1 CLINICAL NEUROLOGY

Neuro-oncology Pub Date : 2025-03-31 DOI:10.1093/neuonc/noaf093

Wenjuan Zhang, Michael P Grams, Rajneet K Oberoi, Ju-Hee Oh, Paul A Decker, Terence T Sio, Surabhi Talele, Zac C Wilson, Margaret A Connors, Katrina K Bakken, Brett L Carlson, Lauren L Ott, Danielle M Burgenske, Erik J Tryggestad, Jeanette E Eckel Passow, William F Elmquist, Jann N Sarkaria

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引用次数: 0

Abstract

Background: Most 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 accomplish this, there are no published studies demonstrating the effect of radiation on drug distribution into the brain or brain tumors.

Methods: Mice 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.

Results: Radiation did not significantly enhance drug delivery into brain tissue for levetiracetam, cefazolin, GNE-317, apitolisib, or nedisertib at any times post-radiation. Even a single, supra-therapeutic dose of radiation (40 Gy) did not significantly affect brain distribution of GNE-317 or apitolisib (P ≥ 0.07) from 16 to 160 hours post-radiation. For brigimadlin, radiation (6 Gy × 5) was associated with a modest but significant increase on drug accumulation only at 72 hours post-radiation (brain-to-plasma ratio 0.014±0.006 vs. 0.025±0.010, respectively; P = 0.04), but not at any other timepoint (24 hr, 15, 28, 94, 133, 183 days; P > 0.05). Similarly, radiation (6 Gy × 5) of orthotopic tumors did not increase levels of brigimadlin in GBM10 or GBM108 or nedisertib in GBM108 (P > 0.05).

Conclusions: Radiation had no meaningful impact of drug delivery into brain or brain tumors for the drugs tested.

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来源期刊

Neuro-oncology 医学-临床神经学

CiteScore

27.20

自引率

6.30%

发文量

1434

审稿时长

3-8 weeks

期刊介绍： Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.