The effect of regadenoson-induced transient disruption of the blood–brain barrier on temozolomide delivery to normal rat brain

Sadhana Jackson, Nicole Anders, Antonella Mangraviti, Teresia M. Wanjiku, Eric W. Sankey, Ann Liu, Henry Brem, Betty Mae Tyler, Michelle Rudek-Renaut, Stuart A Grossman

Research output: Contribution to journalArticle

Abstract

The blood–brain barrier (BBB) significantly reduces the delivery of many systemically administered agents to the central nervous system. Although temozolomide is the only chemotherapy to improve survival in patients with glioblastoma, its concentration in brain is only 20 % of that in blood. Regadenoson, an FDA approved adenosine receptor agonist used for cardiac stress testing, transiently disrupts rodent BBB allowing high molecular weight dextran (70 kD) to enter the brain. This study was conducted to determine if regadenoson could facilitate entry of temozolomide into normal rodent brain. Temozolomide (50 mg/kg) was administered by oral gavage to non-tumor bearing F344 rats. Two-thirds of the animals received a single dose of intravenous regadenoson 60–90 min later. All animals were sacrificed 120 or 360 min after temozolomide administration. Brain and plasma temozolomide concentrations were determined using HPLC/MS/MS. Brain temozolomide concentrations were significantly higher at 120 min when it was given with regadenoson versus alone (8.1 ± 2.7 and 5.1 ± 3.5 µg/g, P 

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalJournal of Neuro-Oncology
Volume126
Issue number3
DOIs
StatePublished - Feb 1 2016

Fingerprint

temozolomide
Brain
Rodentia
Purinergic P1 Receptor Agonists
Central Nervous System Agents
Inbred F344 Rats
Glioblastoma
Dextrans
regadenoson
Molecular Weight
High Pressure Liquid Chromatography

Keywords

  • Blood–brain barrier
  • Brain metastases
  • Brain tumor
  • Pharmacology
  • Regadenoson
  • Temozolomide

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

The effect of regadenoson-induced transient disruption of the blood–brain barrier on temozolomide delivery to normal rat brain. / Jackson, Sadhana; Anders, Nicole; Mangraviti, Antonella; Wanjiku, Teresia M.; Sankey, Eric W.; Liu, Ann; Brem, Henry; Tyler, Betty Mae; Rudek-Renaut, Michelle; Grossman, Stuart A.

In: Journal of Neuro-Oncology, Vol. 126, No. 3, 01.02.2016, p. 433-439.

Research output: Contribution to journalArticle

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