NI-39 * INITIAL EVALUATION OF AN ADENOSINE RECEPTOR AGONIST'S ABILITY TO TRANSIENTLY DISRUPT THE BLOOD BRAIN BARRIER (BBB) IN PATIENTS WITH IN NORMAL BRAINS

Abstract

BACKGROUND: Regadenoson is an FDA approved adenosine receptor agonist which transiently disrupts the BBB in rodents allowing systemically administered high molecular weight dextran (MW 70kD) to enter brain parenchyma. This agent is used clinically for cardiac stress tests in patients unable to exercise in conjunction with 99mTc-sestamibi and cardiac SPECT imaging. 99mTc-sestamibi (MW 600) has been studied as an imaging agent in patients with brain tumors and demonstrates permeability only where there is BBB disruption. METHODS: Patients undergoing clinically indicated and standard pharmacologic cardiac stress tests (10mCi of 99mTc-sestamibi with cardiac imaging followed by 30mCi of 99mTc-sestamibi with regadenoson and cardiac imaging) were eligible. This IRB approved study only added brain SPECT imaging to the pre- and post-regadenoson imaging to determine if more isotope entered the brain following regadenoson administration. RESULTS: Six patients were accrued and pre- and post-regadenoson isotope quantitation in brain parenchyma and overlying scalp were compared to correct for the different 99mTc-sestamibi doses routinely administered in cardiac stress tests. The results were strikingly consistent between patients. Mean isotope counts in the brain were 3.1 times higher (range 2.6-3.4) and in the scalp were 4.2 times higher (range 3.4 to 4.5) post-regadenoson. CONCLUSION: Significantly higher isotope counts were seen in each of these patients with presumably normal brains in the post-regadenoson setting. However, brain imaging with this standard cardiac imaging protocol, which includes different doses of isotope in the pre and post-regadenoson settings, does not allow a definitive statement regarding the ability of this agent to temporarily disrupt the BBB and allow entry of previously impermeable systemically administered compounds into the brain. Further studies are underway to answer this question definitively as transient disruption of the BBB would be of major importance to the field of neuro-oncology.