Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5

Burger, Cyrill; Deschwanden, Alexandra; Ametamey, Simon M.; Johayem, Anass; Mancosu, Bruno; Wyss, Matthias T.; Hasler, Gregor; Buck, Alfred

doi:10.1016/j.nucmedbio.2010.04.107

Cited by 44 publications

(53 citation statements)

References 8 publications

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“…V norm is equivalent to BP ND +1=((V T -V ND )/V ND )+1). 51 mGluR5 has been successfully quantified with this approach in previous studies 46,52,53 and a preclinical study showed that the cerebellum is relatively devoid of mGluR5 and thus suitable as a reference region. 54 …”

Section: Image Acquisition and Data Analysesmentioning

confidence: 99%

“…Before the PET acquisition, a catheter was placed in the left antecubital vein for tracer injection and a low-dose CT was conducted for attenuation correction. In order to avoid inconvenient arterial blood sampling, we relied on a previously evaluated equilibrium paradigm 46,47 based on the premise that a steady-state between tracer concentration in tissue and blood can be obtained. 48 To verify that steady-state of receptor binding was reached after 45min (frames 17 to 19), timeactivity curves were generated for high (ACC, putamen), medium (thalamus), and low receptor density regions (cerebellum) in both hemispheres for all participants.…”

Section: Image Acquisition and Data Analysesmentioning

confidence: 99%

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Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

et al. 2013

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Long-lasting neuroadaptations in the glutamatergic corticostriatal circuitry have been suggested to be responsible for the persisting nature of drug addiction. In particular, animal models have linked the metabotropic glutamate receptor 5 (mGluR5) to drug-seeking behavior and extinction learning. Accordingly, blocking mGluR5s attenuated self-administration of cocaine and other addictive drugs in rats. How these animal findings extend to humans remains unclear. Therefore, we investigated if human cocaine users (CU) exhibit altered mGluR5 availability compared with drug-naïve control subjects. Seventeen male controls (11 smokers) and 18 male cocaine users (13 smokers) underwent positron emission tomography with 11C-ABP688 to quantify mGluR5 availability in 12 volumes of interest in addiction-related brain areas. Drug use was assessed by self-report and quantitative hair toxicology. CU and controls did not significantly differ in regional mGluR5 availability. In contrast, smokers (n=24) showed significantly lower mGluR5 density throughout the brain (mean 20%) compared with non-smokers (n=11). In terms of effect sizes, lower mGluR5 availability was most pronounced in the caudate nucleus (d=1.50, 21%), insula (d=1.47, 20%), and putamen (d=1.46, 18%). Duration of smoking abstinence was positively associated with mGluR5 density in all brain regions of interest, indicating that lower mGluR5 availability was particularly pronounced in individuals who had smoked very recently. Specifically tobacco smoking was associated with lower mGluR5 availability in both CU and controls, while cocaine use was not linked to detectable mGluR5 alterations. These findings have important implications regarding the development of novel pharmacotherapies aimed at facilitating smoking cessation. AbstractLong-lasting neuroadaptations in the glutamatergic corticostriatal circuitry have been suggested to be responsible for the persisting nature of drug addiction. In particular, animal models have linked the metabotropic glutamate receptor 5 (mGluR5) to drug-seeking behavior and extinction learning. Accordingly, blocking mGluR5s attenuated self-administration of cocaine and other addictive drugs in rats. How these animal findings extend to humans remains unclear. Therefore, we investigated if human cocaine users exhibit altered mGluR5 availability compared to drug-naïve control subjects.Seventeen male controls (11 smokers) and 18 male cocaine users (13 smokers) underwent positron emission tomography with 11 C-ABP688 to quantify mGluR5 availability in 12 volumes of interest in addiction-related brain areas. Drug use was assessed by self-report and quantitative hair toxicology.Cocaine users and controls did not significantly differ in regional mGluR5 availability. In contrast, smokers (n=24) showed significantly lower mGluR5 density throughout the brain (mean 20%) compared to non-smokers (n=11). In terms of effect sizes, lower mGluR5 availability was most pronounced in the caudate nucleus (d=1.50, 21%), insula (d=1.47, 20%), and putamen ...

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Section: Image Acquisition and Data Analysesmentioning

confidence: 99%

Section: Image Acquisition and Data Analysesmentioning

confidence: 99%

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

et al. 2013

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“…11 C]ABP688 (Burger et al, 2010). Our method allowed for reliable measurement of the relative distribution volume (DVR), and reduced potential bias due to arterial blood sampling required for absolute quantification.…”

Section: Positron Emission Tomographymentioning

confidence: 99%

“…Our method allowed for reliable measurement of the relative distribution volume (DVR), and reduced potential bias due to arterial blood sampling required for absolute quantification. Equilibrium between the tracer in tissue and blood is achieved 40 min after commencing the radio-ligand infusion (Burger et al, 2010 was administered using an infusion pump (half was given as a bolus over 2 min and the other half infused over the next 58 min). Image acquisition and reconstruction were performed as described earlier (Akkus et al, 2014;Ametamey et al, 2006;Deschwanden et al, 2011;Treyer et al, 2007), using the cerebellum as the reference region.…”

Section: Positron Emission Tomographymentioning

confidence: 99%

Metabotropic glutamate receptor 5 neuroimaging in schizophrenia

Akkus

Treyer

Ametamey

et al. 2017

Schizophrenia Research

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The metabotropic glutamate receptor 5 (mGluR5) is a promising drug target for the treatment of schizophrenia. In this study, we compared mGluR5 distribution volume ration (DVR) in subjects with schizophrenia and healthy controls. Given our previous findings, we matched samples for gender, age, and smoking status. Binding to mGluR5 was determined using positron emission tomography and [ 11 C]ABP688, which binds to an allosteric site with high selectivity. DVR in the 15 individuals with schizophrenia did not differ from that of the 15 controls. In both groups, smoking was associated with marked global reductions in mGluR5 availability (on average 23.8%). In nonsmoking subjects with schizophrenia, there was a positive correlation between mGluR5 DVR in the medial orbitofrontal cortex and the use of antipsychotic drugs (r = 0.9, p =0.019). Because antipsychotic drugs such as clozapine appeared to have indirect effects on mGluR5 signaling, our findings may be clinically relevant. They also provide promising leads for elucidating the high comorbidity between schizophrenia and tobacco addiction. Low mGluR5 DVR in smokers my represent a risk factor for schizophrenia. Alternatively, smoking may counteract the potential upregulation of mGluR5 by antipsychotic drugs.

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“…Furthermore, in several studies, the cerebellum was used as a reference region for the ratio analysis in [ 11 C]ABP688 PET human brain studies using a bolus-infusion protocol. 39,40 Noise in Reference Region Data In this study, we assumed the cerebellar TAC (Supplementary Figure E3) as almost noiseless reference region input function because of its large size. However, in general, the noise level of the reference TAC may change depending on several factors such as size of the region and injection dose.…”

Section: Reference Region For [ 11 C]abp688mentioning

confidence: 99%

Comparative Assessment of Parametric Neuroreceptor Mapping Approaches Based on the Simplified Reference Tissue Model Using [¹¹C]ABP688 PET

Seo

Kim

et al. 2015

J Cereb Blood Flow Metab

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In recent years, several linearized model approaches for fast and reliable parametric neuroreceptor mapping based on dynamic nuclear imaging have been developed from the simplified reference tissue model (SRTM) equation. All the methods share the basic SRTM assumptions, but use different schemes to alleviate the effect of noise in dynamic-image voxels. Thus, this study aimed to compare those approaches in terms of their performance in parametric image generation. We used the basis function method and MRTM2 (multilinear reference tissue model with two parameters), which require a division process to obtain the distribution volume ratio (DVR). In addition, a linear model with the DVR as a model parameter (multilinear SRTM) was used in two forms: one based on linear least squares and the other based on extension of total least squares (TLS). Assessment using simulated and actual dynamic [ 11 C]ABP688 positron emission tomography data revealed their equivalence with the SRTM, except for different noise susceptibilities. In the DVR image production, the two multilinear SRTM approaches achieved better image quality and regional compatibility with the SRTM than the others, with slightly better performance in the TLS-based method. Keywords: neuroreceptor imaging; parametric image; simplified reference tissue model; total least squares; tracer kinetic modeling INTRODUCTIONThe simplified reference tissue model (SRTM) 1 has been used extensively in quantitative studies of a reversibly binding radiotracer using dynamic positron emission tomography (PET) and single photon emission computed tomography, owing to its noninvasiveness and robustness in the estimation of kinetic parameters. [2][3][4][5] The model parameters have been estimated mainly using nonlinear least squares (NLS), which can provide unbiased solutions for parameter estimation from time-activity curves (TACs) with low-or moderate-level noise. In the use of NLS, however, highly noisy data may bring several limitations such as dependency on initial values, long computation time, and a high level of uncertainty. 2,4,6-8 Therefore, the NLS-based standard SRTM (NLS-SRTM) is undesirable for parametric image generation (voxelby-voxel analysis) characterized by large amounts of voxel data with high-level noise. Consequently, the application of NLS-SRTM is limited to the analysis of regional average TACs that are much less noisy than voxel TACs. 2,4

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Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5

Cited by 44 publications

References 8 publications

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

Metabotropic glutamate receptor 5 neuroimaging in schizophrenia

Comparative Assessment of Parametric Neuroreceptor Mapping Approaches Based on the Simplified Reference Tissue Model Using [¹¹C]ABP688 PET

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Evaluation of a bolus/infusion protocol for 11C-ABP688, a PET tracer for mGluR5

Cited by 44 publications

References 8 publications

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans

Metabotropic glutamate receptor 5 neuroimaging in schizophrenia

Comparative Assessment of Parametric Neuroreceptor Mapping Approaches Based on the Simplified Reference Tissue Model Using [11C]ABP688 PET

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Product

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Comparative Assessment of Parametric Neuroreceptor Mapping Approaches Based on the Simplified Reference Tissue Model Using [¹¹C]ABP688 PET