Assessing the dose of regadenoson required to transiently alter blood-brain barrier integrity in patients with infiltrating gliomas

Le résumé fourni par la source

Abstract Background The blood-brain barrier (BBB) severely limits the delivery of therapeutic agents to the brain. Regadenoson, a Food and Drug Administration-approved adenosine A2 agonist, transiently increases BBB permeability in rodents to a 70 kDa dextran. This multi-institutional, NIH-funded study examined regadenoson’s ability to transiently alter BBB permeability in patients with gliomas. Methods Adults with supratentorial gliomas at low risk for regadenoson complications were treated with 1 of the 7 dose levels known to be safe in humans. Successful BBB disruption was defined as a 10-fold increase in vascular permeability (Ktrans) relative to historic benchmarks. This was assessed by dynamic contrast-enhanced perfusion on magnetic resonance imaging in normal-appearing white matter (NAWM) changes in NAWM and non-enhancing tumors were also quantified using contrast-enhanced T1 subtraction maps. Results Seven patients <45 years old with low-grade gliomas were accrued before the study was prematurely closed. Regadenoson was well tolerated. Following regadenoson, Ktrans in NAWM did not reach the targeted Ktrans threshold (0.04 min−1). Normalized subtraction maps of contrast-enhanced T1-weighted MR signal intensity in NAWM did increase an average of 74% ± 22% (P = .016) after regadenoson. Conclusions No dose of regadenoson significantly elevated Ktrans in NAWM. However, the subtraction maps suggest that regadenoson may lead to a measurable change in gadolinium flux. This coupled with strong preclinical data suggests further investigation is warranted. Noninvasive quantification of BBB permeability in patients is feasible and could evaluate different regadenoson schedules, combination therapies, and other approaches to modify BBB permeability which is critical to improving outcomes in patients with brain tumors. Clinical Trial Registration NCI Protocol #: Adult brain tumor consortium 1804, ClinicalTrials.gov Identifier: NCT03971734, Agent(s): Regadenoson, NSC # 811401, commercially available.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.