Jackson Sadhana, George Richard T, Lodge Martin A, Piotrowski Anna, Wahl Richard L, Gujar Sachin K, Grossman Stuart A
Brain Cancer Program, Johns Hopkins University, David H. Koch Cancer Research Building II, 1550 Orleans Street, Room 1M16, Baltimore, MD, 21287, USA.
Heart and Vascular Institute, Johns Hopkins University, 600 N. Wolfe Street, Sheikh Zayed Tower, Baltimore, MD, 21287, USA.
J Neurooncol. 2017 May;132(3):513-519. doi: 10.1007/s11060-017-2404-1. Epub 2017 Mar 17.
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 either Tc-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.
雷加得松是一种经美国食品药品监督管理局（FDA）批准的腺苷受体激动剂，可增加啮齿动物血脑屏障（BBB）的通透性。雷加得松在临床上用于使用不穿过完整血脑屏障的单光子发射计算机断层扫描（SPECT）或计算机断层扫描（CT）成像剂进行药物心脏负荷试验。本研究旨在确定标准剂量的雷加得松是否会短暂破坏人类血脑屏障，使全身给药的成像剂能够以更高浓度进入大脑。接受临床指示的药物心脏负荷试验且无已知颅内疾病的患者符合本研究条件。他们接受了雷加得松（0.4毫克），随后使用用于SPECT的锝-司他米比或用于CT成像的碘克沙醇进行脑成像。对雷加得松给药前后成像剂在脑内的渗透情况进行定量分析[SPECT：放射性计数，CT：亨氏单位（HU）]，并使用配对t检验进行比较。共纳入12例患者（男性占33%，中位年龄60岁）：7例进行SPECT检查，5例进行CT检查。使用平均放射性核素计数（726对757）或HU（29对30）时，雷加得松给药前后的值无显著差异。虽然动物研究表明雷加得松可短暂增加血脑屏障对葡聚糖和替莫唑胺的通透性，但我们无法证明使用FDA批准的用于心脏评估的雷加得松剂量时，完整血脑屏障的人类对比剂渗透情况有变化。需要进一步研究探索雷加得松的替代给药剂量、方案，以及针对脑肿瘤患者的研究；因为短暂破坏血脑屏障以改善药物进入大脑对于改善中枢神经系统恶性肿瘤患者的治疗至关重要。
