| 1. |
- Freiburghaus, Tove, et al.
(författare)
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Low convergent validity of [11C]raclopride binding in extrastriatal brain regions : A PET study of within-subject correlations with [11C]FLB 457
- 2021
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 226
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [11C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers. Instead, the medium affinity radioligand [11C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [11C]raclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both [11C]raclopride and [11C]FLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [11C]raclopride and [11C]FLB 457 BPND extrastriatally (Pearson's R: 0.30-0.56), in contrast to very strong correlations between repeated [11C]FLB 457 measurements (Pearson's R: 0.82-0.98). In comparison, correlations between repeated [11C]raclopride measurements were low to moderate (Pearson's R: 0.28-0.75). These results are likely related to low signal to noise ratio of [11C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [11C]raclopride should be interpreted with caution.
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| 2. |
- Laurell, Gjertrud L, et al.
(författare)
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Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies.
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:3, s. 412-417
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Tidskriftsartikel (refereegranskat)abstract
- The PET ligand 11C-PBR28 (N-((2-(methoxy-11C)-phenyl)methyl)-N-(6-phenoxy-3-pyridinyl)acetamide) binds to the 18-kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, VT, is frequently the reported outcome measure. Since VT is the sum of the ligand-specific distribution volume (VS) and the nondisplaceable-binding distribution volume (VND), differences in VND across subjects and groups will have an impact on VTMethods: Here, we used a recently developed method for simultaneous estimation of VND (SIME) to disentangle contributions from VND and VS Data from 4 previously published 11C-PBR28 PET studies were included: before and after a lipopolysaccharide challenge (8 subjects), in alcohol use disorder (14 patients, 15 controls), in first-episode psychosis (16 patients, 16 controls), and in Parkinson disease (16 patients, 16 controls). In each dataset, regional VT estimates were obtained with a standard 2-tissue-compartment model, and brain-wide VND was estimated with SIME. VS was then calculated as VT - VND VND and VS were then compared across groups, within each dataset. Results: A lower VND was found for individuals with alcohol-use disorder (34%, P = 0.00084) and Parkinson disease (34%, P = 0.0032) than in their corresponding controls. We found no difference in VND between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change VNDConclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.
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| 3. |
- Lee, Maria, et al.
(författare)
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No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis
- 2021
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Ingår i: NPJ SCHIZOPHRENIA. - : Springer Nature. - 2334-265X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [C-11]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (beta = 0.013-0.074, partial r= -0.037-0.273, p = 0.131-0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3-8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.
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| 4. |
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| 5. |
- Svensson, Jonas E., et al.
(författare)
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Serotonin transporter availability increases in patients recovering from a depressive episode
- 2021
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Ingår i: Translational Psychiatry. - : Springer. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [C-11]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p<0.001). [C-11]MADAM binding in patients increased in the composite region after treatment (p=0.01), while no change was observed in the median raphe (p=0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p=0.97) or the median raphe (p=0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.
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