Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

Martínez, Diana; Slifstein, Mark; Nabulsi, Nabeel; Grassetti, Alexander; Urban, Nina; Perez, Audrey; Liu, Fei; Lin, Shu-fei; Ropchan, Jim; Mao, Xiangling; Kegeles, Lawrence S.; Shungu, Dikoma C.; Carson, Richard E.; Huang, Yiyun

doi:10.1016/j.biopsych.2013.06.026

Cited by 70 publications

(53 citation statements)

References 47 publications

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“…In vivo blocking study is not yet available for [ 18 F]FPEB. Similarly, for [ 11 C]ABP688 studies [24–26], CGM has been used as a reference region, but studies indicate the presence of specific binding of [ 11 C]ABP688 in CGM [20, 27, 28]. Thus, based on our findings and other published data, it appears that there is specific mGluR5 binding in the cerebellum.…”

Section: Discussionsupporting

confidence: 75%

Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

Park

Sullivan

Planeta

et al. 2015

Eur J Nucl Med Mol Imaging

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Purpose [18F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [18F]FPEB in the human brain. Methods Seven healthy male subjects were scanned twice, 3–11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162±32 MBq [18F]FPEB. Four methods were used to estimate volume of distribution (VT): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and two-tissue compartment model (2T). Binding potential (BPND) was also estimated using cerebellar white matter (CWM) or grey matter (CGM) as a reference region using EQ, 2T and MA1. Absolute test-retest variability (aTRV) of VT and BPND were calculated for each method. Venous blood measurements (CV) were compared with arterial input (CA) to examine their usability for EQ analysis. Results Regional VT estimated by the four methods displayed a high degree of agreement (r2 ranging from 0.83 to 0.99 between methods), although EQA and EQV overestimated VT by a mean of 9% and 7%, respectively, compared to 2T. Mean aTRV of VT were 11% by EQA, 12% by EQV, 14% by MA1 and 14% by 2T. Regional BPND also agreed well between methods and mean aTRV of BPND was 8–12% (CWM) and 7–9% (CGM). Venous and arterial blood concentrations of [18F]FPEB were well matched during equilibrium (CV=1.01·CA, r2=0.95). Conclusion [18F]FPEB binding shows good test-retest variability with minor differences between analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [18F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.

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Section: Discussionsupporting

confidence: 75%

Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

Park

Sullivan

Planeta

et al. 2015

Eur J Nucl Med Mol Imaging

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“…Similar data were obtained with cocaine in imaging studies in humans (Martinez et al 2014;Milella et al 2014).…”

Section: Brain Imaging Expression Studiessupporting

confidence: 83%

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

2016

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RationaleMost habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor.Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. ObjectiveThe purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. ResultsImaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. ConclusionsAlthough mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off target" effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

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“…As a potent excitatory neurotransmitter GLU has modulatory effects on DA and has actions in striatum and reward pathways. Clinical studies on metabotropic GLU receptor subtype 5 (mGluR5) report GLU differences in cocaine and nicotine addiction and other psychiatric disorders [56 – 59]. GLU is recognized as integral in modulating other neurotransmitters and neuropeptides [60].…”

Section: Molecular Imagingmentioning

confidence: 99%

Corticotropin releasing hormone and imaging, rethinking the stress axis

Contoreggi

2015

Nuclear Medicine and Biology

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The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems has surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we’ve seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and pharmacology. Stress modulates the myriad of neurochemical and networks within and controlled through the central and peripheral nervous system and the effects of stress activation on imaging will be highlighted.

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Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

Cited by 70 publications

References 47 publications

Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Corticotropin releasing hormone and imaging, rethinking the stress axis

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