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C Halldin

Publications and source records attributed to C Halldin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Reproducibility of [11 C]FLB 457 binding in extrastriatal regions.

Extrastriatal D2 dopamine receptors represent an important target of research into the pathophysiology and pharmacotherapy of psychiatric disorders. The high affinity radioligand [11C]FLB 457 makes possible the measurement of low concentrations of D2 receptors in extrastriatal regions using positron emission tomography (PET). The aim of this study was to assess the test/retest variability and reliability of [11C]FLB 457 binding using a reference tissue model. Eight healthy male subjects (aged 20-33 years) underwent two [11C]FLB 457 PET examinations. Radioactivity in the cerebellum was used as the reference. The binding potentials (BPs) for five cortical regions of interest (ROIs) were calculated using the reference tissue model. The BP was also calculated for each pixel in the form of parametric images. Reproducibility was assessed both for the ROI method and for the parametric images. The test/retest reproducibility for [11C]FLB 457 binding was good, with a mean variability ranging from 4.5% for the thalamus to 15.5% for the hippocampus. The parametric images also demonstrated good reproducibility. These results support the suitability of using [11C]FLB 457 for the quantitative evaluation of extrastriatal D2 receptors and for protocols requiring repeated measurements in the same individual.

Adult↗
PubMed2001

No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopride and [(11)C]FLB 457.

OBJECTIVE: The authors' goal was to test the hypothesis of extrastriatal D(2) receptor selectivity as the mechanism of action of clozapine. METHOD: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D(2) receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [(11)C]raclopride was used for determination of D(2) receptor occupancy in the striatum. The radioligand [(11)C]FLB 457 was chosen for determination of D(2) receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex. RESULTS: In patients treated with haloperidol the D(2) receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D(2) receptor occupancy was relatively low in both the striatum and the extrastriatal regions. CONCLUSIONS: The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine.

Adult↗
PubMed2001

PET studies with carbon-11 radioligands in neuropsychopharmacological drug development.

A basic problem in the discovery and development of novel drugs to be used in the treatment of neurological and psychiatric disorders is the absence of relevant in vitro or in vivo animal models that can yield results which can be extrapolated to man. Drug research now benefits from the fast development of functional imaging techniques such as positron emission tomography (PET) which trace radiolabelled molecules directly in the human brain. PET uses molecules that are labelled with short-lived radionuclides and injected intravenously into experimental animals, human volunteers or patients. The most frequent approach is to study how an unlabelled drug inhibits specific binding of a well characterised selective PET radioligand. The alternative direct approach is to radiolabel a new potential drug and to trace its uptake, anatomical distribution and binding in brain. Furthermore, the effects of a novel drug on physiological-biochemical parameters, such as glucose metabolism or blood flow, can also be assessed. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action, to correlate pharmacological and physiological effects, and to optimise clinical treatment.

Animals↗
PubMed2001

Brain radioligands--state of the art and new trends.

Non-invasive radioligand imaging methods for brain receptor studies use either short-lived positron-emitting radionuclides such as 11C and 18F for positron emission tomography (PET) or single photon-emitting radionuclides such as 123I for single photon emission computed tomography (SPECT). PET and SPECT use radioligands which are injected intravenously into experimental animals, human volunteers or patients. The main applications of radioligands in brain research concern human neuropsychopharmacology and the discovery and development of novel drugs to be used in thetherapy of neurological and psychiatric disorders. A basic problem in PET and SPECT brain receptor studies is the lack of useful radioligands with appropriate binding characteristics. Prerequisite criteria need to be satisfied for a radioligand to reveal target binding sites in vivo. This section will discuss these important criteria and also review recent examples in neuroreceptor radioligand development such as selective radioligands for brain monoamine transporters.

Animals↗
PubMed2000

Autoradiographic localization of 5-HT(2A) receptors in the human brain using [(3)H]M100907 and [(11)C]M100907.

M100907 (MDL 100907, R-(+)-alpha-(2, 3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol++ +) is a new selective antagonist of 5-HT(2A) receptors. The compound has been labeled with (11)C and proved useful for in vivo studies of 5-HT(2A) receptors using positron emission tomography (PET). In the present study the distribution of 5-HT(2A) receptors was examined in the postmortem human brain using whole hemisphere autoradiography and [(3)H]M100907 and [(11)C]M100907. The autoradiograms showed very dense binding to all neocortical regions, whereas the hippocampus was only weakly labeled with [(3)H]M100907. Other central brain regions, such as the basal ganglia and thalamus, showed low [(3)H]M100907 binding, reflecting low densities of 5-HT(2A) receptors. The cerebellum or structures of the brain stem were virtually devoid of 5-HT(2A) receptors. [(11)C]M100907 gave images qualitatively similar to those of [(3)H]M100907, although with lower spatial resolution. The labeling of human 5-HT(2A) receptors with [(3)H]M100907 was inhibited by the addition of the 5-HT(2A) receptor blockers ketanserin or SCH 23390 (10 microM), leaving a very low background of nonspecific binding. The 5-HT(1A) receptor antagonist WAY-100635 and the D(2)-dopamine receptor antagonist raclopride had no effect on the binding of [(3)H]M100907. The selective labeling of 5-HT(2A) receptors with [(3)H]M100907 clearly shows that this compound is suitable for further studies of the human 5-HT(2A) receptor subtype in vitro. The in vitro autoradiography of the distribution of 5-HT(2A) receptors obtained with radiolabeled M100907 provides detailed qualitative and quantitative information on the distribution of 5-HT(2A)-receptors in the human brain as well as reference information for the interpretation of previous initial results at much lower resolution in humans in vivo with PET and [(11)C]M100907.

Adult↗
PubMed2000

Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.

The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.

Adult↗
PubMed2000

Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson's disease.

OBJECTIVE: To investigate whether dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the caudate-putamen are affected in PD. BACKGROUND: Alterations in striatal D2-like dopamine receptors in PD have been extensively demonstrated using PET, but there are no studies focusing on extrastriatal D2/3Rs. METHODS: Fourteen unmedicated patients with idiopathic early PD with predominantly left-sided symptoms, 14 levodopa-medicated patients with advanced PD, and 20 normal age-matched controls were examined using PET. PET scanning was performed with a novel high-affinity D2/3R radioligand ([11C]FLB 457) and a PET scanner in three-dimensional mode. RESULTS: In advanced PD, the binding potential of [11C]FLB 457 in the dorsolateral prefrontal cortex was decreased by 40% (p < 0.01), in the anterior cingulate cortex by 20% (p < 0.01), and in the medial thalamus by 17% (p < 0.05) compared with healthy controls. In early PD, the extrastriatal [11C]FLB 457 binding potentials were not significantly different compared with the control group. However, the binding potential in the anterior cingulate cortex (29%; p < 0. 05) was higher in early PD compared with advanced PD. CONCLUSIONS: These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.

Brain↗
PubMed2000

Effects of chronic 17beta-estradiol treatment on the serotonin 5-HT(1A) receptor mRNA and binding levels in the rat brain.

Acute 17beta-estradiol treatment had been shown to downregulate the 5-HT(1A) receptor mRNA expression in limbic areas of the female rat brain. The aim of the present study was to determine the effects of chronic 17beta-estradiol treatment on 5-HT(1A) receptor mRNA expression and 5-HT(1A) receptor binding in ovariectomized female rats. Using in situ hybridization histochemistry, no alterations were found on the 5-HT(1A) receptor mRNA levels after the estradiol treatment (2 weeks). Radioligand autoradiographic studies using the selective 5-HT(1A) receptor antagonist [(3)H]WAY-100635 revealed reduced receptor binding in the amygdala, hippocampus, perirhinal cortex, and motor cortex after estradiol treatment, whereas no changes were observed in the piriform or retrosplenial cortex. Thus, the previous findings together with the present results indicate that estradiol-induced alterations in 5-HT(1A) receptor mRNA expression appears within hours, but diminishes with chronic treatment when significant changes on the receptor-protein level are apparent. The effects of estradiol treatment on the 5-HT(1A) receptor binding in the limbic areas suggest that estrogen can modulate functions such as learning, memory, cognition, emotional processing, and social behavior. Consequently, estradiol modulation of 5-HT(1A) receptor circuits might be a possible pathway for the estrogen influence in the expression of psychiatric and neurological disorders such as Alzheimer's disease, affective disorders, and schizophrenia.

Animals↗
PubMed2000

Effect of amphetamine on extrastriatal D2 dopamine receptor binding in the primate brain: a PET study.

[(11)C]raclopride binding to D2 dopamine receptors in the striatum is sensitive to drug-induced changes of endogenous dopamine concentration. We recently developed the new radioligand [(11)C]FLB 457, which is suitable for positron emission tomography (PET) studies of extrastriatal D2 dopamine receptors. The purpose of this PET study was to examine the effect of amphetamine on [(11)C]FLB 457 binding in extrastriatal regions. Each of three cynomolgus monkeys was examined at baseline conditions, 15 min and 3 h after I.V. injection of amphetamine (2 mg/kg). The effect of amphetamine was calculated from the ratio of specific [(11)C]FLB 457 binding to the binding in the cerebellum, a region which was used as reference for free and nonspecific binding in the brain. The changes of the ratio in the striatum, the thalamus, and the neocortex were between -1.2% and -15.5% at 15 min and -2.1% and -16.3% at 3 h, respectively, after amphetamine administration. The reductions of the binding ratios in the extrastriatal regions are similar to those reported for [(11)C]raclopride binding in the striatum. These data in a limited series of monkeys suggest that [(11)C]FLB 457 binding to D2 dopamine receptors in extrastriatal regions is sensitive to changes in the concentration of endogenous dopamine.

Amphetamine↗
PubMed2000

High 5HT2A receptor occupancy in M100907-treated schizophrenic patients.

RATIONALE: Selective drugs are required to test the hypothesis whether antipsychotic effects may be induced or modulated by 5HT(2A) receptor antagonism. M100907 (previously known as MDL 100,907) is a highly selective 5HT(2A) antagonist in clinical development. OBJECTIVE: To test if the suggested clinical dose of 20 mg M100907 daily induces high 5HT(2A) receptor occupancy in patients with schizophrenia. METHODS: The 5HT(2A) receptor occupancy was determined in two patients with schizophrenia treated with M100907, 20 mg once a day. Positron emission tomography (PET) with (11)C-labeled M100907, was performed prestudy and under steady state conditions. Clinical ratings were performed weekly. RESULTS: Clinical treatment with M100907, 20 mg daily induced a very high 5HT(2A) receptor occupancy in the frontal cortex of both patients (>90%). M100907 was well tolerated. One patient improved minimally and one patient became minimally worse during treatment. CONCLUSIONS: The results confirm that an oral dose of 20 mg per day ensures adequate 5HT(2A) receptor occupancy for clinical proof of concept. The sample is too small to allow conclusions about the clinical effect.

Adult↗
PubMed2000

Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease.

RATIONALE: The density of the M2 subtype of muscarinic acetylcholine receptors (mAChR) has been shown to be reduced in the brain of patients with Alzheimer's disease (AD). It is therefore of interest to develop a brain imaging method for diagnostic purposes. Z-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo1-propen-3-yl)-alpha-phenylacetat e (Z-IQNP) is a muscarinic antagonist with high affinity for the M2 subtype. OBJECTIVE: The pharmacological characteristics and topographic distribution of radiolabelled Z-IQNP as a radioligand for the M2 mAChR subtype were examined in vitro and in vivo. METHODS: Z-IQNP was labelled with 1251 and 123I. Autoradiography was performed on whole-hemisphere cryosections from human post mortem brains. SPECT was performed in a cynomolgus monkey. RESULTS: Autoradiography showed binding of [125I]Z-IQNP in all brain regions, which was inhibited by the non-selective muscarinic antagonist scopolamine. The addition of BIBN 99, a compound with high affinity for the M2 subtype, inhibited [125I]Z-IQNP binding particularly in the cerebellum, which has a high density of the M2 subtype. SPECT demonstrated high uptake of [123I]Z-IQNP in all brain regions. The binding was markedly reduced in all brain regions after pretreatment with the non-selective muscarinic antagonist dexetimide and also the M1 antagonist biperiden. Dexetimide markedly inhibited [123I]Z-IQNP binding in the cerebellum, which is consistent with a high density of M2-receptors in this region. The sigma receptor binding compound DuP 734 had no effect on Z-IQNP binding either in vitro or in vivo. CONCLUSIONS: This study indicates that radiolabelled Z-IQNP has high specificity for mAChR with higher affinity for the M2 than the M1 subtype and negligible affinity for sigma recognition sites both in vitro and in vivo. [123I]Z-IQNP should be useful for future SPECT studies in AD for examination of the density of M2 receptors particularly in the cerebellum.

Alzheimer Disease↗
PubMed2000

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography.

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D2 receptors with SPET using [123I]epidepride.

Adult↗
PubMed2000

PET-Determination of robalzotan (NAD-299) induced 5-HT(1A) receptor occupancy in the monkey brain.

The serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor subtype is of central interest in research, particularly in the area of pathophysiology and pharmacological treatment of psychiatric disorders. Robalzotan (generic name for NAD-299) is a new putative drug that binds with high selectivity and affinity to 5-HT(1A)-receptors in the rodent brain in vitro and in vivo. The aim of this positron emission tomography study was to determine 5-HT(1A) receptor occupancy in the cynomolgus monkey brain in vivo after IV injection of robalzotan. Two healthy monkeys were examined with Positron Emission Tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635, the first after IV administration of 2 microg/kg and 20 microg/kg, and the second after 10 microg/kg and 100 microg/kg IV. 5-HT(1A) receptor occupancy was calculated using an equilibrium-ratio analysis. Robalzotan occupied 5-HT(1A) receptors in a dose-dependent and saturable manner. The highest 5-HT(1A) receptor occupancy (70-80%) was attained after 100 microg/kg. The relationship between robalzotan drug concentration and 5-HT(1A) receptor occupancy could be described by a hyperbolic function, which can be used to guide the selection of appropriate doses for the initial studies in man. The study further corroborates that quantitative neuroimaging of receptor binding has potentials for the evaluation and dose finding of new CNS drugs.

Animals↗
PubMed2000

High specific radioactivity (1R,2S)-4-[(18)F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart.

The radiolabeled catecholamine analogue (1R, 2S)-6-[(18)F]fluorometaraminol (6-[(18)F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[(18)F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[(18)F]fluorometaraminol (4-[(18)F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/micromol). In the present study, we demonstrate in rats that 4-[(18)F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[(18)F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[(18)F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[(18)F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[(18)F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[(18)F]FMR is a promising alternative to 6-[(18)F]FMR for myocardial neuronal mapping with PET in humans.

Adrenergic Uptake Inhibitors↗
PubMed2000

Radioligands for the study of brain 5-HT(1A) receptors in vivo--development of some new analogues of way.

[Carbonyl-(11)C]WAY-100635 (WAY) has proved to be a very useful radioligand for the imaging of brain 5-HT(1A) receptors in human brain in vivo with positron emission tomography (PET). WAY is now being applied widely for clinical research and drug development. However, WAY is rapidly cleared from plasma and is also rapidly metabolised. A comparable radioligand, with a higher and more sustained delivery to brain, is desirable since these properties might lead to better biomathematical modelling of acquired PET data. There are also needs for other types of 5-HT(1A) receptor radioligands, for example, ligands sensitive to elevated serotonin levels, ligands labelled with longer-lived fluorine-18 for distribution to "satellite" PET centres, and ligands labelled with iodine-123 for single photon emission computerised tomography (SPECT) imaging. Here we describe our progress toward these aims through the exploration of WAY analogues, including the development of [carbonyl-(11)C]desmethyl-WAY (DWAY) as a promising, more brain-penetrant radioligand for PET imaging of human 5-HT(1A) receptors, and (pyridinyl-6-halo)-analogues as promising leads for the development of radiohalogenated ligands.

Animals↗
PubMed2000

Use of PET and the radioligand [carbonyl-(11)C]WAY-100635 in psychotropic drug development.

Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine(1A) (5-HT(1A)) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT(1A) receptor now benefits from the highly selective radioligand [carbonyl-(11)C]WAY-100635 (WAY) for quantitative determination of 5-HT(1A) receptors in the primate and human brain in vivo using PET. In this paper, three studies are reviewed to demonstrate the suitability of WAY as radioligand for quantification of central 5-HT(1A) receptors in brain and as an applicable tool for drug development. In the first study a monkey model was used to characterize WAY binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive drugs such as buspirone and pindolol occupies 5-HT(1A) receptors in the primate brain. Pindolol is an beta-adrenoreceptor antagonist with a high affinity to 5-HT(1A) receptors. This drug has been suggested in combination with selective serotonin reuptake inhibitors for the treatment of depression and was given to healthy males in the second study. Pindolol induced a marked inhibition of central 5-HT(1A) receptors as calculated by the ratio-analysis method and simplified reference tissue model, 2 h after administration of 10 mg as a single oral dose. This observation suggests that pindolol may have a role for the suggested potentiation of selective serotonin reuptake inhibitor treatment of depression. The third study was on robalzotan (NAD-299), a recently developed 5-HT(1A) receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 microg/kg IV occupied 5-HT(1A) receptors in a dose-dependent and saturable manner with a maximal calculated occupancy of 70-80%. The relationship between robalzotan plasma concentration and 5-HT(1A) receptor occupancy could be described by a hyperbolic function that was used to guide the selection of appropriate doses in man. In a subsequent PET study of robalzotan binding to 5-HT(1A) receptors in the living human brain, similar results have been replicated recently. These studies reviewed here illustrate and corroborate that quantitative neuroimaging of receptor binding has potential for the evaluation and dose finding of new central nervous system drugs.

Animals↗
PubMed2000

Carbon-11 pb-12: an attempt to visualize the dopamine d(4) receptor in the primate brain with positron emission tomography.

The dopamine D(4) receptor (D(4)R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a novel, high-affinity ( K(i)=0.040 nM) and selective D(4)R ligand. We radiolabeled PB-12 with carbon-11 (t(1/2) 20.4 min) by O-methylation of the corresponding desmethyl analogue N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-hydroxybenzamide (LM-190) with [(11)C]methyl triflate. Derivative LM-190 was prepared by condensing 3-hydroxybenzoic acid with the appropriate amine. For the radiolabeling, the incorporation yield was >90% and the total synthesis time including high performance liquid chromatography (HPLC) purification was about 35 min. The specific radioactivity of [(11)C]PB-12 at time of injection was 67-118 GBq x micromol(-1). PET studies in a cynomolgus monkey showed a high uptake and widespread distribution of radioactivity in the brain, including the neocortex and thalamus. About 40% of total radioactivity in plasma represented unchanged radioligand at 60 min after injection as determined by HPLC. Pretreatment with the D(4)R ligand 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrollo[2,3-b]pyridine (L-745,870) prior to radioligand injection failed to demonstrate receptor-specific binding in the monkey brain. Furthermore, the brain radioactivity distribution was left unaffected by pretreating with unlabeled PB-12. This failure to detect a D(4)R-specific signal may be related to a very low density of the D(4)R in primate brain, insufficient binding affinity of the radioligand, and a high background of nonspecific binding. It can be concluded from these findings that [(11)C]PB-12 is not suitable to visualize the D(4)R in the primate brain with PET.

Animals↗