脊髓多巴胺D2/D3受体：使用（18）F/（11）C-法螺必利对大鼠进行体内和体外成像
Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using (18)F/(11)C-fallypride.
作者信息
Kaur Jasmeet, Khararjian Armen, Coleman Robert A, Constantinescu Cristian C, Pan Min-Liang, Mukherjee Jogeshwar
机构信息
Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697.
Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697.
出版信息
Nucl Med Biol. 2014 Nov-Dec;41(10):841-7. doi: 10.1016/j.nucmedbio.2014.08.002. Epub 2014 Aug 8.
OBJECTIVES
The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands (18)F-fallypride and (11)C-fallypride.
METHODS
Male Sprague-Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a (18)F-fallypride scan or a (11)C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro.
RESULTS
In vitro studies showed (18)F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of (18)F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both (18)F-fallypride and (11)C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the (18)F-fallypride in spinal cord sections.
CONCLUSIONS
Our studies showed (18)F-fallypride and (11)C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.
目的
已知脊髓由多巴胺能细胞支配，这些细胞具有源自延髓和脑桥的儿茶酚胺能投射，且脊髓中的多巴胺能传递对感觉和运动功能至关重要。我们的目标是使用正电子发射断层扫描（PET）配体（18）F-法螺必利和（11）C-法螺必利评估并比较大鼠脊髓中多巴胺D2/D3受体的成像能力。
方法
所有体外和体内研究均使用雄性斯普拉格-道利大鼠。脊髓和脑切片用于体外放射自显影和离体放射自显影。对于体内研究，动物接受（18）F-法螺必利扫描或（11）C-法螺必利PET扫描。然后收获脊髓和脑，快速冷冻并进行离体成像。对于体内分析，以小脑为参考的洛根图用于评估结合电位（BP）。组织比率用于离体分析。在体外对脊髓切片使用氯氮平、氟哌啶醇评估药物作用，并评估多巴胺。
结果
体外研究显示（18）F-法螺必利与浅表背角（SDH）、背角（DH）、腹角（VH）和中央部（PC）结合。在颈段切片中，最大量的结合似乎在SDH。离体研究显示，与纹状体中观察到的相比，SDH中约6%的（18）F-法螺必利。脊髓中（18）F-法螺必利和（11）C-法螺必利的体内分析与纹状体以外区域的分析结果相当。氟哌啶醇和氯氮平使脊髓切片中超过75%的（18）F-法螺必利移位。
结论
我们的研究显示（18）F-法螺必利和（11）C-法螺必利在体外和体内脊髓中均有结合。结合模式与脊髓中已知的多巴胺D2/D3受体分布密切相关。
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