DDEL-09QUANTIFICATION OF TRANSIENT BLOOD BRAIN BARRIER DISRUPTION FOLLOWING THE SYSTEMIC ADMINISTRATION OF REGADENOSON

Abstract

BACKGROUND: The blood brain barrier (BBB) makes it difficult for oral or intravenous chemotherapy to achieve therapeutic concentrations in brain parenchyma. Regadenoson is an adenosine receptor agonist which transiently disrupts the BBB, allowing systemically administered high molecular weight dextran (MW 70kD) to enter normal rodent brain. Our recent studies with this compound suggest that temozolomide concentrations in rodent brain are also increased by regadenoson. This FDA approved agent is used routinely for cardiac stress tests in patients unable to exercise along with visipaque and cardiac computed tomography (CT) imaging. Visipaque (MW 1550) typically only enters brain where there is significant disruption of the BBB. This study is being conducted to determine if regadenoson will allow more contrast to enter normal human brain. METHODS: Patients without known intracranial disease who were undergoing clinically indicated pharmacologic cardiac stress tests (visipaque with cardiac CT followed by visipaque with regadenoson and cardiac CT) were eligible. This IRB approved study only added brain CT pre- and post-regadenoson. Contrast delivery was measured in hounsfield units (HU), at the level of the basal ganglia, within the cortex, deep gray and white matter. A total of 27 patients are required to assist in comparison analysis of regional contrast uptake. A matched-pairs t-test was performed to determine if the difference was significant. RESULTS: Five of the 27 patients have been accrued and analyzed. There was no difference in contrast following visipaque alone and visipaque with regadenoson (29.3HU vs 30.2HU respectively, P = 0.06). CONCLUSION: Early results from this ongoing study suggest that even accounting for the additional visipaque dose there is a trend towards increased contrast enhancement following regadenoson administration in patients with presumably normal brains. Transient disruption of the BBB to facilitate drug entry using an FDA approved agent could be of significant importance to the field of neuro-oncology.