Pet imaging of D2-like dopamine receptors in the human brain with [18F]desmethoxyfallypride

Gründer, Gerhard; Piel, Markus; Schirrmacher, Ralf; Hamkens, W.; Schmitt, Ulrich; Benz, P.; Hiemke, Christoph; Rösch, Frank

doi:10.1016/s0924-977x(99)80593-8

Cited by 25 publications

(39 citation statements)

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“…This is in line with the observation that striatal D 2 receptor occupancy is markedly underestimated when a high-affinity radiotracer ([ 76 Br]FLB-457) is used, and striatal and extrastriatal D 2 receptor occupancy is determined at the same early time after radiotracer injection (Xiberas et al, 2001;Vernaleken et al, 2004). On the other hand, it has been argued that cortical binding is underestimated with [ 11 C]FLB-457 (Gründer et al, 2003b;Mukherjee et al, 2001).…”

Section: Introductionsupporting

confidence: 83%

“…The [ 18 F]fallypride was synthesized as described for [ 18 F]desmethoxyfallypride (Gründer et al, 2003b). The tosylated precursor ((S)-N-[(1-allyl)-2-pyrrolidinyl)-methyl]-5-(3-toluenesulfonyloxy-propyl)-2,3-dimethoxybenzamide (5 mg, 10 mmol) was dissolved in 1 ml acetonitrile, treated for 5 min at 851C with potassium carbonate (5 mg, 36 mmol), and subsequently reacted with [ 18 F]fluoride for 20 min at 851C.…”

Section: Radiochemistrymentioning

confidence: 99%

“…BP were calculated on a voxelwise basis using the Lammertsma Simplified Reference Tissue Model, which is based on a two-tissue compartment model (Gründer et al, 2003b;Lammertsma and Hume, 1996). The cerebellum was chosen as a reference region, since it is generally considered dopamine receptor free.…”

Section: Data Acquisition and Analysismentioning

confidence: 99%

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The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Gründer

Landvogt²,

Vernaleken

et al. 2005

Neuropsychopharmacol

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Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D 2 /D 3 dopamine receptors in human striatum. Here, the occupancy of D 2 /D 3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [ 18 F]fallypride PET scan. Receptor occupancy was calculated as percent reduction in binding potential relative to unblocked values measured in seven normal volunteers. Mean D 2 /D 3 receptor occupancy was statistically significantly higher in cortical (inferior temporal cortex 55%) than in striatal regions (putamen 36%, caudate 43%, po0.005). While the maximum attainable receptor occupancy E max approached 100% both in the striatum and cortex, the plasma concentration at 50% of E max (ED 50 ) was much higher in the putamen (950 ng/ml) than in the inferior temporal cortex (333 ng/ml). Clozapine binds preferentially to cortical D 2 /D 3 receptors over a wide range of plasma concentrations. This selectivity is lost at extremely high plasma levels. Occupancy of cortical receptors approaches 60% with plasma clozapine in the range 350-400 ng/ml, which corresponds to the threshold for antipsychotic efficacy of clozapine. Extrastriatal binding of clozapine may be more relevant to its antipsychotic actions than striatal. However, further studies with an intraindividual comparison of untreated vs treated state are desirable to confirm this finding.

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Section: Introductionsupporting

confidence: 83%

Section: Radiochemistrymentioning

confidence: 99%

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The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Gründer

Landvogt²,

Vernaleken

et al. 2005

Neuropsychopharmacol

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“…13,14 In the present study, the sensitivity of the method may have been increased by using a higher-resolution PET scanner (HRRT), fallypride labelled with 18 F instead of 11 C, the lower intersubject variability, the nonpharmacological challenge used, and the behaviour-based division of subgroups. 28,30,64 and the present study confirms that informative data can be (C) The scatterplot shows the negative correlation between baseline SN/VTA BP ND and craving score. Path c and path c′ are, respectively, the "total effect" and the "direct effect" of X on Y.…”

Section: Limitationssupporting

confidence: 69%

Cocaine cue–induced dopamine release in the human prefrontal cortex

Milella

Fotros

Gravel

et al. 2016

jpn

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IntroductionThe prefrontal cortex (PFC) integrates and interprets sensory information, processing value, directing attention, and planning actions based on experience.1,2 In cocaine-dependent individuals, these regions and processes are engaged by drug-related cues, increasing the likelihood of craving and drug pursuit.3-5 For each of these effects, dopamine (DA) is a plausible contributing transmitter. Mesocortical DA transmission plays a critical role in cognitive and executive functions, 6 and, in laboratory animals, DA infusions into the PFC reinstate cocaine-seeking behaviours 7,8 while DA depletion or receptor antagonists reduce the drug's reinforcing efficacy. 9Based on these observations, it has been proposed that PFC abnormalities seen in cocaine-dependent individuals 10 are related at least in part to experience-dependent changes in DA transmission. 11,12 Dopamine release in the human PFC and striatum can be measured following an amphetamine challenge with positron emission tomography (PET) and the 18 F-labelled tracer fallypride. 13,14 More recently, the radioligand's PFC sensitivity to nonpharmacological manipulations of the DA system has also been demonstrated using psychological stressors.15-17 Here, we used [ 18 F]fallypride and high-resolution PET to assess the ability of drug-related cues to elicit DA release in the PFC of volunteers meeting criteria for current cocaine dependence. Given the role of DA in conditioned approach and incentive learning, 18 we hypothesized that exposure to familiar, drugrelated stimuli would enhance DA signalling in prefrontal and, in particular, orbitofrontal regions, contributing to the generation of motivational states that lead to drug seeking. 5,19Based on earlier reports identifying an association between PFC activation and self-reported craving, 3,20,21 a positive correlation between PFC DA release and craving was predicted. , 2015; Revised Sept. 9, 2015; Accepted Oct. 19, 2015; Early-released Feb. 23, 2016 DOI: 10.1503 Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods: We used highresolution positron emission tomography with [

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“…In this group, the following variable diagnoses were made: schizophrenia (n = 38), schizoaffective disorder (n = 9), transient psychosis (n = 2), cyclothymic disorder (n = 1), and personality disorder (n = 1). (Hamacher et al, 1986;Grü nder et al, 2003) by using the tosylated precursor ((S)-N-[(1-allyl)-2-pyrrolidinyl)methyl]-5-(3-toluenesulfonyloxy-propyl)-2-ethoxybenzamide. Quality control before injection included determination of chemical and radiochemical purity, specific activity, pH, and absence of pyrogens.…”

Section: Subjectsmentioning

confidence: 99%

The applicability of SRTM in [¹⁸F]fallypride PET investigations: Impact of scan durations

Vernaleken

Peters

Raptis

et al. 2011

J Cereb Blood Flow Metab

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The high-affinity radioligand [18 F]fallypride (FP) is frequently used for quantification of striatal/ extrastriatal D 2/3 receptors and the receptor occupancies of antipsychotics (APs). Its 110 minutes half-life allows long scan durations. However, the optimum scan duration is a matter of debate. This investigation focuses on scan-duration-related effects on simplified reference tissue model (SRTM) results and the time point of transient equilibrium in a large sample of dynamic FP positron emission tomography (PET) scans. Fifty drug-free and 50 AP-treated subjects underwent FP-PET scans (180 minutes scan duration). The binding potential (BP ND ) of the putamen, thalamus, and temporal cortex were calculated using the SRTM and the transient equilibrium model. Furthermore, receptor occupancies were calculated for AP-treated patients. Transient equilibrium in the unblocked putamen occurred after 121 ± 29.6 minutes. The transient equilibrium occurred much earlier in the extrastriatal regions or under AP treatment. Stepwise scan shortening caused BP ND underestimations of 0.58% for the first 10-minute reduction (putamen, SRTM), finally reaching 5.76% after 1 hour scan-time reduction. We observed preferential extrastriatal AP binding irrespective of the analytical method. [18 F]fallypride scan durations of 180 minutes reliably reach equilibrium even in D 2/3 -receptor-rich regions. Moderate reductions in FP scan durations only caused small changes to SRTM results even in receptor-rich regions. Apparently, the D 2/3 receptor occupancy results of APs, especially preferential extrastriatal binding observations, are not relevantly biased by inappropriate scan durations.

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Pet imaging of D2-like dopamine receptors in the human brain with [18F]desmethoxyfallypride

Cited by 25 publications

References 0 publications

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Cocaine cue–induced dopamine release in the human prefrontal cortex

The applicability of SRTM in [¹⁸F]fallypride PET investigations: Impact of scan durations

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Pet imaging of D2-like dopamine receptors in the human brain with [18F]desmethoxyfallypride

Cited by 25 publications

References 0 publications

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

Cocaine cue–induced dopamine release in the human prefrontal cortex

The applicability of SRTM in [18F]fallypride PET investigations: Impact of scan durations

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The applicability of SRTM in [¹⁸F]fallypride PET investigations: Impact of scan durations