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A Method for the In Vivo Investigation of the Serotonergic 5‐HT 2 Receptors in the Human Cerebral Cortex Using Positron Emission Tomography and 18 F‐Labeled Setoperone
Author(s) -
Blin Jerôme,
Sette Giuliano,
Fiorelli Marco,
Bletry Olivier,
Elghozi Jean Luc,
Crouzel Christian,
Baron Jean Claude
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb01229.x
Subject(s) - serotonergic , positron emission tomography , in vivo , cerebral cortex , human brain , 5 ht receptor , neuroscience , brain positron emission tomography , receptor , nuclear magnetic resonance , chemistry , positron , nuclear medicine , serotonin , preclinical imaging , physics , medicine , biology , biochemistry , nuclear physics , microbiology and biotechnology , electron
Following previous validation in baboons, we have studied the characteristics of [ 18 F]setoperone as a radioligand for investigating serotonergic 5‐hydroxytryptamine 2 (5‐HT 2 ) receptors in the normal, unmedicated human brain with positron emission tomography (PET); subjects orally pretreated with therapeutic amounts of ketanserin, sulpiride, or prazosin were also studied to evaluate the specificity and sensitivity of [ 18 F]setoperone brain specific binding. In controls (n = 10), the tracer showed a clear‐cut retention in both frontal cortex and striatum (known to contain a high density of 5‐HT 2 receptors) relative to cerebellum (known to be devoid of 5‐HT 2 receptors). In the seven young controls (20–39 years old), the frontal cortex/cerebellum and striatum/cerebellum ratios increased during the first hour to reach similar values of 2.53 ± 0.12 and 2.38 ± 0.11 (mean ± SEM), respectively, and were essentially stable during the second hour. Pretreatment with ketanserin (a 5‐HT 2 blocker) significantly reduced the frontal cortex/cerebellum ratio to 0.7–1.0 at 65 min, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. During sulpiride treatment (a D 2 blocker), the frontal cortex/cerebellum ratio was not altered, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. With prazosin pretreatment (an α 1 ‐adrenergic blocker), neither the frontal cortex/cerebellum nor the striatum/cerebellum ratio was modified. These data in humans with PET demonstrate that [ 18 F]setoperone labels with high sensitivity and selectivity 5‐HT 2 receptors in the frontal cortex; in striata, however, binding is to both 5‐HT 2 and D 2 receptors. The deproteinated‐to‐whole plasma radioactivity concentration ratio increased with time following injection. The mean percentage of intact [ 18 F]setoperone, in deproteinated plasma, was 82, 74, 53, 45, 30, and 22% at 5, 10, 20, 30, 60, and 110 min following injection, respectively. These data indicate that [ 18 F]setoperone (a) is significantly bound to plasma proteins and (b) is significantly metabolized into several labeled metabolites that are much more hydrophilic than setoperone and, hence, presumably do not cross the blood–brain barrier. These results suggest the suitability of [ 18 F]setoperone data for modeling of 5‐HT 2 receptor binding in brain.