title: 4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Leiden, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Van der Krogt
authors.forename: E K
authors.initials: EK
authors.lastname: Pauwels
authors.forename: P A
authors.initials: PA
authors.lastname: Van Doremalen
authors.forename: G
authors.initials: G
authors.lastname: Wijnhoven
authors.forename: S
authors.initials: S
authors.lastname: Reiffers
authors.forename: C F
authors.initials: CF
authors.lastname: Van Valkenburg
authors.forename: O J
authors.initials: OJ
authors.lastname: Buruma
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism*; D014316:Tritium
chemical_list: D007457:Iodine Radioisotopes; D011954:Receptors, Dopamine; D014316:Tritium; D013134:Spiperone; C042868:4-iodospiperone