Focused ultrasound-mediated blood-brain barrier opening to enhance temozolomide delivery in glioblastoma: a systematic review of preclinical and early clinical evidence.
Level 5 - mechanism / opinion, no new human data
Systematic review synthesizing predominantly preclinical animal models (6 studies) and early preliminary clinical studies (3 studies).
PubMed 42399440 · doi:10.1007/s10143-026-04367-x
What was done
The authors conducted a systematic review searching PubMed, Cochrane Library, ClinicalTrials.gov, Embase, and Scopus through December 2025. They identified preclinical glioblastoma (GBM) models and human studies evaluating focused ultrasound (FUS)-mediated blood-brain barrier opening (BBBO) combined with systemic temozolomide (TMZ) that reported pharmacologic, therapeutic, or safety outcomes.
What was found
Nine studies met inclusion criteria: 6 preclinical and 3 early clinical studies, all utilizing microbubbles to facilitate BBBO. Preclinical studies consistently demonstrated increased intratumoral TMZ delivery, improved tumor control, and prolonged survival with FUS plus TMZ compared to TMZ alone, with 2 studies directly quantifying enhanced intratumoral drug exposure (specific numbers not reported in the abstract). Clinical studies showed reproducible, MR-guided BBBO with no procedure-related neurological complications, though human survival and pharmacokinetic data remain preliminary.
Why it matters
FUS-mediated BBBO is a noninvasive approach to overcome the blood-brain barrier and augment chemotherapy delivery in glioblastoma. This review confirms technical feasibility and preclinical biological activity while highlighting the absence of confirmed clinical efficacy.
Limits
The total evidence base is small (9 studies total, only 3 in humans). The abstract reports no quantitative values for human patient sample sizes, survival metrics, or pharmacokinetic parameters, and human clinical efficacy remains unproven.
Cited by
- supports Focused ultrasound can be used to focally open the blood-brain barrier at targeted locations in the brain for drug delivery.