[18F]<scp>JNJ</scp>42259152 binding to phosphodiesterase 10A, a key regulator of medium spiny neuron excitability, is altered in the presence of cyclic <scp>AMP</scp>

Ooms, Maarten; Attili, Bala; Celen, Sofie; Verbruggen, Alfons; Laere, Koen Van; Bormans, Guy

doi:10.1111/jnc.13855

Cited by 15 publications

(23 citation statements)

References 43 publications

(88 reference statements)

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“…(d) Finally, the possibility of change in the number of PDE10 molecules per dendritic spine and a change in affinity of PDE10a for [ 11 C]IMA107 cannot be excuded as factors that led to the inability to detect an increase in MSN spine density in cocaine users. The latter is relevant as recent studies have shown that the concentration of cAMP alters the affinity of PDE10a for its ligand (Ooms et al, ).…”

Section: Discussionmentioning

confidence: 99%

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET

Tollefson

Gertler

Himes

et al. 2018

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Phosphodiesterase-10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self-administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder (“cocaine users”) compared to controls. PDE10a availability was measured with [11C]IMA107 and PET in 15 cocaine users and 15 controls matched for age, gender, and nicotine status. Cocaine users with no comorbid psychiatric, medical, or drug abuse disorders were scanned following two weeks of outpatient-monitored abstinence. [11C]IMA107 binding potential relative to nondisplaceable uptake (BPND) in the regions of interest were derived with the simplified reference tissue method. No significant effect of diagnosis on BPND was demonstrated using linear mixed modeling with [11C]IMA107 BPND as the dependent variable and regions of interest as a repeated measure. There were no significant relationships between BPND and clinical rating scales. To the extent that PDE10a is a valid proxy for MSN spine density, these results do not support its increase in recently abstinent cocaine users.

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Section: Discussionmentioning

confidence: 99%

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET

Tollefson

Gertler

Himes

et al. 2018

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“…Phosphodiesterase 10A (PDE10A), a member of phosphodiesterases (PDEs), is an enzyme involved in deactivation of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cAMP and cGMP, respectively). It is highly expressed in MSNs, where it regulates their excitability [70]. As mentioned earlier, MSNs are severely deregulated in various neurodegenerative pathologies, including HD.…”

Section: Phosphodiesterase 10amentioning

confidence: 93%

Huntington’s Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers

et al. 2020

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Huntington’s disease (HD) is a fatal neurodegenerative disease caused by a CAG expansion mutation in the huntingtin gene. As a result, intranuclear inclusions of mutant huntingtin protein are formed, which damage striatal medium spiny neurons (MSNs). A review of Positron Emission Tomography (PET) studies relating to HD was performed, including clinical and preclinical data. PET is a powerful tool for visualisation of the HD pathology by non-invasive imaging of specific radiopharmaceuticals, which provide a detailed molecular snapshot of complex mechanistic pathways within the brain. Nowadays, radiochemists are equipped with an impressive arsenal of radioligands to accurately recognise particular receptors of interest. These include key biomarkers of HD: adenosine, cannabinoid, dopaminergic and glutamateric receptors, microglial activation, phosphodiesterase 10 A and synaptic vesicle proteins. This review aims to provide a radiochemical picture of the recent developments in the field of HD PET, with significant attention devoted to radiosynthetic routes towards the tracers relevant to this disease.

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“…Later, Ooms et al have investigated the effect of alterations in cAMP levels on [ 18 F]JNJ-42259152 binding to PDE10A in the striatum homogenates. Increased affinity of this radiotracer for PDE10A was observed in the presence of cAMP, which seems to have an important role in the allosteric regulation of PDE10A [62]. Figure 14), and their in vivo evaluation in nonhuman primates [63].…”

Section: Phosphodiester-10a Enzyme Inhibitorsmentioning

confidence: 96%

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET)

Gomes

Silva

2020

Molecules

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The need for increasingly personalized medicine solutions (precision medicine) and quality medical treatments, has led to a growing demand and research for image-guided therapeutic solutions. Positron emission tomography (PET) is a powerful imaging technique that can be established using complementary imaging systems and selective imaging agents—chemical probes or radiotracers—which are drugs labeled with a radionuclide, also called radiopharmaceuticals. PET has two complementary purposes: selective imaging for diagnosis and monitoring of disease progression and response to treatment. The development of selective imaging agents is a growing research area, with a high number of diverse drugs, labeled with different radionuclides, being reported nowadays. This review article is focused on the use of pyrazoles as suitable scaffolds for the development of 18F-labeled radiotracers for PET imaging. A brief introduction to PET and pyrazoles, as key scaffolds in medicinal chemistry, is presented, followed by a description of the most important [18F]pyrazole-derived radiotracers (PET tracers) that have been developed in the last 20 years for selective PET imaging, grouped according to their specific targets.

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[18F]JNJ42259152 binding to phosphodiesterase 10A, a key regulator of medium spiny neuron excitability, is altered in the presence of cyclic AMP

Cited by 15 publications

References 43 publications

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET

Huntington’s Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET)

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[18F]JNJ42259152 binding to phosphodiesterase 10A, a key regulator of medium spiny neuron excitability, is altered in the presence of cyclic AMP

Cited by 15 publications

References 43 publications

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [11C]IMA107 and PET

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [11C]IMA107 and PET

Huntington’s Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET)

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Product

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Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET

Imaging phosphodiesterase‐10a availability in cocaine use disorder with [¹¹C]IMA107 and PET