The effect of regadenoson on the integrity of the human blood-brain barrier, a pilot study.
Regadenoson is an FDA approved adenosine receptor agonist which increases blood-brain barrier (BBB) permeability in rodents. Regadenoson is used clinically for pharmacologic cardiac stress testing using SPECT or CT imaging agents that do not cross an intact BBB. This study was conducted to determine if standard doses of regadenoson transiently disrupt the human BBB allowing higher concentrations of systemically administered imaging agents to enter the brain. Patients without known intracranial disease undergoing clinically indicated pharmacologic cardiac stress tests were eligible for this study. They received regadenoson (0.4 mg) followed by brain imaging with either99mTc-sestamibi for SPECT or visipaque for CT imaging. Pre- and post-regadenoson penetration of imaging agents into brain were quantified [SPECT: radioactive counts, CT: Hounsfield units (HU)] and compared using a matched-pairs t-test. Twelve patients (33% male, median 60 yo) were accrued: 7 SPECT and 5 CT. No significant differences were noted in pre- and post-regadenoson values using mean radionuclide counts (726 vs. 757) or HU (29 vs. 30). While animal studies have demonstrated that regadenoson transiently increases the permeability of the BBB to dextran and temozolomide, we were unable to document changes in the penetration of contrast agents in humans with intact BBB using the FDA approved doses of regadenoson for cardiac evaluation. Further studies are needed exploring alternate regadenoson dosing, schedules, and studies in patients with brain tumors; as transiently disrupting the BBB to improve drug entry into the brain is critical to improving the care of patients with CNS malignancies.
Brain Cancer Program, Johns Hopkins University, David H. Koch Cancer Research Building II, 1550 Orleans Street, Room 1M16, Baltimore, MD, 21287, USA.
Sadhana
S
Jackson
Heart and Vascular Institute, Johns Hopkins University, 600 N. Wolfe Street, Sheikh Zayed Tower, Baltimore, MD, 21287, USA.
Richard T
RT
George
Nuclear Medicine, Russell H. Morgan Dept. of Radiology and Radiological Sciences, Johns Hopkins University, 601 Caroline St, Baltimore, MD, 21231, USA.
Martin A
MA
Lodge
Brain Cancer Program, Johns Hopkins University, David H. Koch Cancer Research Building II, 1550 Orleans Street, Room 1M16, Baltimore, MD, 21287, USA.
Anna
A
Piotrowski
Nuclear Medicine, Russell H. Morgan Dept. of Radiology and Radiological Sciences, Johns Hopkins University, 601 Caroline St, Baltimore, MD, 21231, USA.|Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO, 63110, USA.
Richard L
RL
Wahl
Radiology and Radiological Science, Johns Hopkins University, 600 N. Wolfe Street, Sheikh Zayed Tower, Baltimore, MD, 21287, USA.
Sachin K
SK
Gujar
Brain Cancer Program, Johns Hopkins University, David H. Koch Cancer Research Building II, 1550 Orleans Street, Room 1M16, Baltimore, MD, 21287, USA. grossman@jhmi.edu.
Stuart A
SA
Grossman
D058908:Adenosine A2 Receptor Agonists / Q000493:pharmacokinetics*; D000368:Aged; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000000981:diagnostic imaging; D055426:Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; D003287:Contrast Media; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods; D010865:Pilot Projects; D011687:Purines / Q000493:pharmacokinetics*; D011720:Pyrazoles / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals; D013669:Technetium Tc 99m Medronate; D014057:Tomography, X-Ray Computed
D058908:Adenosine A2 Receptor Agonists; D003287:Contrast Media; D011687:Purines; D011720:Pyrazoles; D019275:Radiopharmaceuticals; C430916:regadenoson; D013669:Technetium Tc 99m Medronate
99mTc-sestamibi; Blood–brain barrier permeability; Drug entry; Regadenoson; Visipaque