Imaging Kappa Opioid Receptors in the Living Brain with Positron Emission Tomography

The regional binding of N1′ -([11C]methyl)naltrindole (MeNTI), a selective δ-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two-and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of δ-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of δ receptor binding in the human brain with 11C-labeled MeNTI.

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Data-driven analysis of kappa opioid receptor binding in major depressive disorder measured by positron emission tomography

Translational Psychiatry ◽

10.1038/s41398-021-01729-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kelly Smart ◽

Ashley Yttredahl ◽

Maria A. Oquendo ◽

J. John Mann ◽

Ansel T. Hillmer ◽

...

Keyword(s):

Positron Emission Tomography ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Rating Scale ◽

Kappa Opioid Receptor ◽

Anterior Cingulate ◽

Emission Tomography ◽

Kappa Opioid ◽

Major Depressive ◽

Positron Emission

AbstractPreclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [11C]GR103545 in 10 unmedicated, currently depressed individuals with major depressive disorder (MDD; 32.6 ± 6.5 years, 5 women) and 13 healthy volunteers (34.8 ± 10 years, 6 women). Independent component analysis was performed to identify spatial patterns of coherent variance in KOR binding (tracer volume of distribution, VT) across all subjects. Expression of each component was compared between groups and relationships to symptoms were explored using the 17-item Hamilton Depression Rating Scale (HDRS). Three components of variation in KOR availability across ROIs were identified, spatially characterized by [11C]GR103545 VT in (1) bilateral frontal lobe; (2) occipital and parietal cortices, right hippocampus, and putamen; and (3) right anterior cingulate, right superior frontal gyrus and insula, coupled to negative loading in left middle cingulate. In MDD patients, component 3 was negatively associated with symptom severity on the HDRS (r = −0.85, p = 0.0021). There were no group-wise differences in expression of any component between patients and controls. These preliminary findings suggest that KOR signaling in cortical regions relevant to depression, particularly right anterior cingulate, could reflect MDD pathophysiology.

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