Given the importance of transiently opening the BBB to facilitate drug entry, further research in this area is desperately needed to improve the outcome of patients with CNS malignancies. For both primary and metastatic tumors, treatment options are very limited and/or exhibit poor sustainability for growth inhibition, and invasion. Several agents have been investigated in the past as a means to transiently “open” the BBB, but very few studies or laboratory investigations are being conducted to identify optimal genes, signaling pathways, or receptors so as to design drugs to influence CNS permeability. Regadenoson may be a potential agent, but more studies are needed to define the optimal dose and dosing schedule with the desired effect on CNS vasculature. These questions, along with the proper dosing and schedule of regadenoson, remain to be further studied, in order to explain our negative findings and improve chances of future success in enhancing transient BBB permeability.