The early rapid rise of temozolomide seen with regadenoson administration can be attributed to the fast acting modulation that results from adenosine receptor activation [16, 24, 36]. Preclinical studies demonstrated the effect of regadenoson on brain vasculature with 0.05 mg/kg dosage per mouse (human equivalent dosing of 0.004 mg/kg); which is less than the standard cardiac stress dosing of 0.006 mg/kg per patient. Yet, despite these preclinical studies utilizing lower than standard regadenoson dosing, increased CNS penetration of 70 kD dextran and temozolomide was observed [16, 19, 24]. Interestingly, these studies in rodents demonstrated a bell shaped dose/effect curve, suggesting that regadenoson doses too high or too low result in minimal changes in BBB disruption. With this clinical study, we opted to use the standard clinical dosing of regadenoson (0.4 mg). This FDA approved agent is used daily in the clinical setting of patients with suspected heart disease to induce vasodilation. Clinically, patients receive one dose with associated cardiac imaging. We hypothesized that because approximately 26% of patients with suspected cardiac disease experience brief headaches after regadenoson administration, it is possible that headaches may be a direct correlate/biomarker for the presence or degree of BBB disruption. We opted to start with the clinical dosing of regadenoson as a means to increase temozolomide CNS entry. While optimal dosing has been determined for cardiac stress testing, optimal dosing and schedule of administration has yet to be determined with a focus on BBB permeability. Thus, it is plausible that increased or decreased standard regadenoson dosing could optimally augment CNS temozolomide entry. These studies of varied regadenoson dosing impacting the BBB permeability have not been performed to date in humans.