Pharmacological and anatomical evidence implicates striatal dopamine receptors in Tourette syndrome (TS). Nevertheless, results of positron emission tomography (PET) studies of the dopamine system in TS have been inconsistent. We investigated striatal D2/3 dopamine receptors in TS using the radioligands [(11) C]raclopride and [(11) C]-(+)-PHNO, an agonist that binds preferentially to D3 receptors, thus allowing higher sensitivity and measurement of receptors in a high affinity state. Eleven adults with TS and 11 matched healthy control (HC) participants underwent [(11) C]raclopride and [(11) C]-(+)-PHNO PET scans. General linear model was used for voxelwise contrasts of striatal binding potentials (BPND ) between TS and HC participants. Analysis of variance was performed to investigate main effect of radioligand. In addition, BPND values were extracted for ventral, motor, and associative striatum. Finally, we examined the relationship between BPND measures and symptom severity in TS participants. Main effects analyses showed that [(11) C]-(+)-PHNO BPND was higher in ventral striatum, whereas [(11) C]raclopride BPND was higher in motor and associative striatum. There were no significant group differences between TS and HC. Furthermore, TS and HC participants had similar [(11) C]-(+)-PHNO and [(11) C]raclopride BPND in the three striatal subregions. Moreover, there was no significant correlation between BPND and symptom severity. TS and HC participants had similar striatal D2/3 receptor availability measures. These results challenge the assumption that striatal dopamine receptors have a major role in the pathophysiology of TS. Consistent with previous findings, [(11) C]-(+)-PHNO localized preferentially to ventral striatal, D3 receptor-rich regions, in contrast to [(11) C]raclopride, which localized preferentially in the dorsal striatum.
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http://dx.doi.org/10.1002/hbm.22793 | DOI Listing |
Biol Psychiatry
October 2024
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; The Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, Connecticut. Electronic address:
Ann Nucl Med
April 2023
Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University, 2-1, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Objective: C-PHNO is a PET radioligand most specific to dopamine D receptor (DR). The long scan duration of 120 min used in quantification of C-PHNO binding to DR in previous studies is challenging to subjects. The main objective of this study was to investigate the effects of shorter scan times on the binding of C-PHNO to DR and test-retest reliability using the latest digital whole-body PET system.
View Article and Find Full Text PDFMethods Mol Biol
December 2022
Department of Internal Medicine, Division of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
Noninvasive quantitative imaging of beta-cells can provide information on changes in cellular transporters, receptors, and signaling proteins that may affect function and/or loss of mass, both of which contribute to the loss of insulin secretion and glucose regulation of patients with type 1 or type 2 diabetes (T1D/T2D). We have developed and optimized the use of two positron emission tomography (PET) radioligands, [F]FP-(+)-DTBZ and [C](+)-PHNO, targeting beta-cell VMAT2 and dopamine (D2/D3) receptors, respectively. Here we describe our optimized methodology for the clinical use of these two tracers for quantitative PET imaging of beta-cell biomarkers in vivo.
View Article and Find Full Text PDFSynapse
January 2023
Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
The brain plays a major role in controlling the desire to eat. This meta-analysis aimed to assess the association between dopamine receptor (DR) availability and dopamine transporter (DAT) availability, measured using positron emission tomography, and obesity. We performed a systematic search of MEDLINE (from inception to November 2020) and EMBASE (from inception to November 2020) for articles published in English using the keywords "dopamine receptor," "dopamine transporter," "obesity," and "neuroimaging.
View Article and Find Full Text PDFMol Psychiatry
August 2022
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported.
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