Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers

Matuskey, David; Dias, Mark; Naganawa, Mika; Pittman, Brian; Henry, Shannan; Li, Songye; Gao, Hong; Ropchan, Jim; Nabulsi, Nabeel; Carson, Richard E.; Huang, Yiyun

doi:10.1038/s41386-019-0379-7

Cited by 27 publications

(11 citation statements)

References 68 publications

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“…First, a nonlinear transformation grid was estimated between the AAL template and each subject's magnetic resonance (MR) image, using BioImage Suite software (v2.5; http://www.bioimagesuite.com). This nonlinear coregistration algorithm is a method first described in 2001 and subsequently used in multiple studies . Then, the subject's summed PET image (0–10 minutes postinjection) was coregistered to their MR image using a 6‐parameter rigid (linear) registration estimated with a mutual information algorithm (FMRIB's Linear Image Registration Tool, FMRIB Software Library).…”

Section: Methodsmentioning

confidence: 99%

“…This nonlinear coregistration algorithm is a March 2020 331 method first described in 2001 30 and subsequently used in multiple studies. 29,[31][32][33][34][35] Then, the subject's summed PET image (0-10 minutes postinjection) was coregistered to their MR image using a 6-parameter rigid (linear) registration estimated with a mutual information algorithm (FMRIB's Linear Image Registration Tool, FMRIB Software Library). Please see Figure 1 for a diagram of image registration processing.…”

Section: Imagingmentioning

confidence: 99%

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Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging

Matuskey

Tinaz

Wilcox

et al. 2020

Annals of Neurology

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140

109

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Objective Parkinson disease is characterized by motor and nonmotor symptoms, reduced striatal dopamine signaling, and loss of dopamine neurons in the substantia nigra. It is now known that the pathological process in Parkinson disease may begin decades before the clinical diagnosis and include a variety of neuronal alterations in addition to the dopamine system. Methods This study examined the density of all synapses with synaptic vesicle glycoprotein 2A (SV2A) in Parkinson disease subjects with mild bilateral disease (n = 12) and matched normal controls (n = 12) using in vivo high‐resolution positron emission tomographic imaging as well as postmortem autoradiography in an independent sample with Parkinson disease (n = 15) and normal controls (n = 13) in the substantia nigra and putamen. Results A group‐by‐brain region interaction effect (F10, 22 = 3.52, p = 0.007) was observed in the primary brain areas with in vivo SV2A binding. Post hoc analyses revealed that the Parkinson disease group exhibited lower SV2A in the substantia nigra (−45%; p < 0.001), red nucleus (−31%; p = 0.03), and locus coeruleus (−17%; p = 0.03). Exploratory analyses also revealed lower SV2A binding in clinically relevant cortical areas. Using autoradiography, we confirmed lower SV2A in the substantia nigra (−17%; p < 0.005) and nonsignificant findings in the putamen (−4%; p = 0.06). Interpretation This work provides the first evidence of synaptic loss in brainstem nuclei involved in the pathogenesis of Parkinson disease in living patients. SV2A imaging holds promise for understanding synaptic changes central to the disease. Ann Neurol 2020;87:329–338

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Section: Methodsmentioning

confidence: 99%

Section: Imagingmentioning

confidence: 99%

Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging

Matuskey

Tinaz

Wilcox

et al. 2020

Annals of Neurology

Self Cite

140

109

View full text Add to dashboard Cite

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“…Only recently have radiotracers been developed to target KOP receptors, including the agonist tracers [ 11 C]GR103545 and [ 11 C]EKAP and the antagonist tracer [ 11 C]LY2795050. These radiotracers have been evaluated in primates (237–240) and humans (241–244).…”

Section: The Opioid Receptor Systemmentioning

confidence: 99%

Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders

et al. 2019

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Opioid use in the United States has steadily risen since the 1990s, along with staggering increases in addiction and overdose fatalities. With this surge in prescription and illicit opioid abuse, it is paramount to understand the genetic risk factors and neuropsychological effects of opioid use disorder (OUD). Polymorphisms disrupting the opioid and dopamine systems have been associated with increased risk for developing substance use disorders. Molecular imaging studies have revealed how these polymorphisms impact the brain and contribute to cognitive and behavioral differences across individuals. Here, we review the current molecular imaging literature to assess how genetic variations in the opioid and dopamine systems affect function in the brain’s reward, cognition, and stress pathways, potentially resulting in vulnerabilities to OUD. Continued research of the functional consequences of genetic variants and corresponding alterations in neural mechanisms will inform prevention and treatment of OUD.

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“…A pilot PET study with the κOR-ligand [ 11 C]GR103545 ( 25 ) did not reveal any binding differences between healthy control and patients suffering from major depression [190]. However, a [ 11 C]EKAP ( 27 ) κOR study in healthy volunteers showed an inverse correlation between social status and [ 11 C]salvinorin A ( 33 ) binding in widespread brain areas, with a special association occurring in brain regions mediating reward or aversion [191]. Given the association between social stress and depression, one might have expected covariance κORs in the two studies.…”

Section: Clinical Studiesmentioning

confidence: 99%

A Survey of Molecular Imaging of Opioid Receptors

et al. 2019

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The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as μ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-11C]morphine, -codeine and -heroin did not show significant binding in vivo. [11C]Diprenorphine ([11C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the μ-preferring agonist [11C]carfentanil ([11C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [11C]DPN or [11C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate μ-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of μORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the δ-preferring endogenous opioid enkephalin, have been used in PET studies of δORs, and [11C]GR103545 is validated for studies of κORs. Structures such as [11C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of δ-, κ-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry.

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Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers

Cited by 27 publications

References 68 publications

Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging

Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging

Molecular Imaging of Opioid and Dopamine Systems: Insights Into the Pharmacogenetics of Opioid Use Disorders

A Survey of Molecular Imaging of Opioid Receptors

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