种代号为ABCB1的成像的影响22()函数对大脑动力学胃复安。
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Pottier G,玛丽,Goutal年代,Auvity年代,Peyronneau MA Stute年代,Boisgard R,道F, Buvat我Caille F, Tournier N
种代号为ABCB1的成像的影响22()函数对大脑动力学胃复安。
J诊断。2016年2月,57(2):309 - 14所示。doi: 10.2967 / jnumed.115.164350。Epub 2015年11月19日。
- PubMed ID
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26585058 (在PubMed]
- 文摘
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未标记的:胃复安对中枢神经系统(CNS)建议患者大脑实质分布。之前的数据显示,胃复安大脑动力学可能还是由磷酸腺苷盒(ABC)在血脑屏障转运蛋白表达。我们使用(11)C-metoclopramide PET成像阐明转运的动力学影响函数胃复安接触到大脑。方法:22 (11)C-metoclopramide运输(P-gp;ABCB1)和乳腺癌耐药蛋白(BCRP;在细胞ABCG2)测试使用吸收化验overexpressing P-gp BCRP。(11)C-metoclopramide大脑动力学比较使用宠物老鼠(n = 4 - 5)药物剂量的胃复安的缺失和存在(3毫克/公斤),有或没有P-gp抑制使用静脉tariquidar(8毫克/公斤)。(11)C-metoclopramide大脑分布(VT基于洛根情节分析)和大脑动力学(2-tissue-compartment模型)具有测量或一个imaged-derived输入函数。等离子体和大脑radiometabolites使用radio-high-performance液相色谱分析进行了研究。结果:(11)C-metoclopramide被选择性P-gp BCRP运输。 Pharmacologic dose did not affect baseline (11)C-metoclopramide brain kinetics (VT = 2.28 +/- 0.32 and 2.04 +/- 0.19 mLcm(-3) using microdose and pharmacologic dose, respectively). Tariquidar significantly enhanced microdose (11)C-metoclopramide VT (7.80 +/- 1.43 mLcm(-3)) with a 4.4-fold increase in K1 (influx rate constant) and a 2.3-fold increase in binding potential (k3/k4) in the 2-tissue-compartment model. In the pharmacologic situation, P-gp inhibition significantly increased metoclopramide brain distribution (VT = 6.28 +/- 0.48 mLcm(-3)) with a 2.0-fold increase in K1 and a 2.2-fold decrease in k2 (efflux rate), with no significant impact on binding potential. In this situation, only parent (11)C-metoclopramide could be detected in the brains of P-gp-inhibited rats. CONCLUSION: (11)C-metoclopramide benefits from favorable pharmacokinetic properties that offer reliable quantification of P-gp function at the blood-brain barrier in a pharmacologic situation. Using metoclopramide as a model of CNS drug, we demonstrated that P-gp function not only reduces influx but also mediates the efflux from the brain back to the blood compartment, with additional impact on brain distribution. This PET-based strategy of P-gp function investigation may provide new insight on the contribution of P-gp to the variability of response to CNS drugs between patients.