Soucy J P, Lafaille F, Lemoine P, Mrini A, Descarries L
Département de Médecine Nucléaire, Hôpital Notre-Dame, Montréal, Canada.
J Nucl Med. 1994 Nov;35(11):1822-30.
Radiolabeled ligands of monoamine transporters have already been used to visualize cerebral monoamine innervation by tissue autoradiography and by PET or SPECT in vivo.
A sampling technique was developed to allow for both the autoradiographic counting of serotonin (5-HT) axonal varicosities, labeled by uptake and storage of [3H]5-HT, and the measurement of the binding of [3H]cyanoimipramine ([3H]CYI), a specific 5-HT transporter ligand, in adjacent slices of adult rat neostriatum. The experiments were conducted in normal, decreased (after 5,7-dihydroxytryptamine lesions in adults) or increased (after 6-hydroxydopamine lesions in neonates) states of neostriatal 5-HT innervation.
In normal tissue, the regional density of [3H]CYI binding faithfully reproduced rostrocaudal variations in the number of [3H]5-HT-labeled axonal varicosities. Pairs of values from all three experimental groups showed a highly significant linear correlation (r = 0.93) between the density of [3H]CYI binding and the number of 5-HT varicosities per cubic millimeter of tissue. The intercept of the regression line was close to zero; this confirmed the selectivity of the ligand.
Under drug-free conditions, specific [3H]CYI binding is a good quantitative index of 5-HT innervation density in brain tissue and is not significantly up- or downregulated on 5-HT denervation or hyperinnervation. When it is adequately labeled, such a ligand might therefore be appropriate to quantify regional 5-HT innervation in vivo by PET or SPECT. The present approach should also be useful to select ligands to quantify 5-HT and monoamine systems.
单胺转运体的放射性标记配体已被用于通过组织放射自显影以及体内正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）来可视化脑内单胺神经支配。
开发了一种采样技术，可对经[³H]5-羟色胺（5-HT）摄取和储存标记的5-羟色胺能轴突膨体进行放射自显影计数，并测量[³H]氰米帕明（[³H]CYI，一种特异性5-羟色胺转运体配体）在成年大鼠新纹状体相邻切片中的结合情况。实验在新纹状体5-羟色胺能神经支配正常、减少（成年后经5,7-二羟基色胺损伤）或增加（新生鼠经6-羟基多巴胺损伤）的状态下进行。
在正常组织中，[³H]CYI结合的区域密度如实地再现了[³H]5-羟色胺标记的轴突膨体数量的前后变化。来自所有三个实验组的成对数值显示，[³H]CYI结合密度与每立方毫米组织中5-羟色胺膨体数量之间存在高度显著的线性相关性（r = 0.93）。回归线的截距接近零；这证实了该配体的选择性。
在无药物条件下，特异性[³H]CYI结合是脑组织中5-羟色胺能神经支配密度的良好定量指标，在5-羟色胺能去神经支配或神经支配过强时不会显著上调或下调。因此，当它被充分标记时，这样的配体可能适合通过PET或SPECT在体内定量区域5-羟色胺能神经支配。本方法对于选择用于定量5-羟色胺和单胺系统的配体也应是有用的。
