Adenosine appears to play an important role in the integrity of the BBB [16–21]. The function of adenosine is controlled by four G-protein coupled receptors: A1, A2A, A2B and A3. A1 and A3 receptors inhibit and A2A and A2B stimulate downstream activation of adenylate cyclase resulting in calcium influx and vasodilation [17, 22]. Inhibitory receptor A1 and stimulating receptor A2A exhibit high expression and functionality within the heart and brain; specifically impacting local vasodilation [18, 21, 23]. Regadenoson is an FDA-approved A2A receptor agonist which is routinely used for pharmacologic stress testing in patients with suspected cardiac disease and an inability to perform an exercise stress test. Single-photon emission computed tomography (SPECT) is often performed with a radiotracer to measure myocardial perfusion both at rest and then at the time of stress induced by regadenoson administration. Pre-clinical models have demonstrated the effectiveness of A1 and/or A2A receptor agonism to increase BBB permeability to a 70 kD dextran molecule in both mice and rat brains . The large dextran was detected in the brain for up to 180 min following a single injection in both mice and rats. In additional studies that evaluated CNS barrier permeability with regadenoson, there was a 60% increase in temozolomide brain concentrations in non-tumor bearing rats, without changing the systemic pharmacology of temozolomide . These findings prompted clinical studies of regadenoson followed by brain SPECT and CT imaging to evaluate CNS permeability differences, but there was no detectable change in permeability of the BBB in patients . However, no previous study has directly investigated whether regadenoson is capable of increasing temozolomide concentrations in the human brain.