Zimmer L, Pain F, Mauger G, Plenevaux A, Le Bars D, Mastrippolito R, Pujol J F, Renaud B, Lanièce P
INSERM U512, Neuropharmacologie et Neurochimie University Lyon I, Lyon, France.
Eur J Nucl Med Mol Imaging. 2002 Sep;29(9):1237-47. doi: 10.1007/s00259-002-0866-6. Epub 2002 Jul 25.
The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal beta-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [(18)F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using beta-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the DRN of anaesthetised rodents.
本研究的目的是证明一种最近开发的β(+)范围敏感型脑内探针（β-微探针）测量[(18)F]MPPF结合动力学的能力，[(18)F]MPPF是一种有充分文献记载的5-羟色胺能受体配体，用于麻醉大鼠的中缝背核（DRN）。这个中脑核含有高浓度的5-HT(1A)受体，已知与抗抑郁药的作用有关。本研究面临的困难在于DRN的尺寸小于β-微探针的检测体积。在研究的第一部分，我们通过放射自显影和蒙特卡罗模拟从理论角度研究了这种测量的可行性。我们确定了靠近DRN的最佳β-微探针位置，并验证了这种配置能够准确测定核内[(18)F]MPPF的特异性结合。在研究的第二部分，我们测量了DRN中[(18)F]MPPF结合的体内时间-浓度曲线，并与小脑进行了比较。未标记的5-HT(1A)拮抗剂注射（MPPF或WAY-100635）后[(18)F]MPPF结合的位移证实了其在DRN中的特异性。此外，我们验证了使用β-微探针监测和通过微透析同时验证来研究芬氟拉明注射诱导的细胞外5-羟色胺增加对DRN中[(18)F]MPPF结合的影响的可行性。我们的理论模拟得到了实验结果的证实，证明了这种新设备能够在体内监测[(18)F]MPPF在麻醉啮齿动物DRN中的结合。
