Van der Krogt J A, Pauwels E K, Van Doremalen P A, Wijnhoven G, Reiffers S, Van Valkenburg C F, Buruma O J
Department of Pharmacology, University of Leiden, The Netherlands.
Int J Rad Appl Instrum B. 1992 Oct;19(7):759-63. doi: 10.1016/0883-2897(92)90137-n.
Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4-[123I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [3H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.
放射性碘化螺哌隆对于通过单光子发射计算机断层扫描（SPECT）在活体人脑中进行多巴胺（DA）受体研究具有重要意义。受[11C]-N-甲基螺哌隆所获数据的启发，我们合成了4-[123I]碘螺哌隆，并研究了该配体与大鼠纹状体膜的体外结合特性以及在大鼠脑不同区域的体内分布。体外结合实验表明，这种放射性配体对DA受体的亲和力比螺哌隆低约10倍，且未观察到如[3H]螺哌隆所示的特异性结合。未观察到布他拉莫的置换作用。体内研究表明，4-[123I]碘螺哌隆和[3H]螺哌隆分别在纹状体组织中富集，其浓度分别是小脑组织中的1.9倍和3.5倍。氟哌啶醇预处理在很大程度上阻止了这种积累。然而，鉴于所获得的靶标与非靶标比率，我们认为这种在富含DA受体的脑区中的积累对于SPECT临床受体成像并无前景。
