4-[ 123I]Iodospiperone as a ligand for dopamine DA receptors: In vitro and in vivo experiments in a rat model

• Published in: International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology Vol. 19; no. 7; pp. 759 - 763
• Main Authors: Van Der Krogt, J.A., Pauwels, E.K.J., Van Doremalen, P.A.P.M., Wijnhoven, G., Reiffers, S., Van Valkenburg, C.F.M., Buruma, O.J.S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.1992; Pergamon
• Subjects: Animals; Binding, Competitive; Biological and medical sciences; Brain - metabolism; Cell Membrane - metabolism; Contrast media. Radiopharmaceuticals; Corpus Striatum - metabolism; Iodine Radioisotopes; Male; Medical sciences; Organ Specificity; Pharmacology. Drug treatments; Rats; Rats, Wistar; Receptors, Dopamine - analysis; Receptors, Dopamine - metabolism; Spiperone - analogs & derivatives; Spiperone - metabolism; Tritium; In vivo; Dopamine; Ligand; Dopamine receptor; Animal; Brain (invertebrata); Exploration; In vitro; Positron emission tomography
• ISSN: 0883-2897
• 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.