Development of PET/SPECT Ligands for the Serotonin Transporter

Scheffel, Ursula; Dannals, R. F.; Suehiro, Makiko; Ga, Ricaurte; Fi, Carroll; Kuhar, MJ; Hn, Wagner

doi:10.1037/e495902006-009

Cited by 8 publications

(7 citation statements)

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“…It has already been suggested that damage to the serotoninergic central raphe neurons of the brain stem might underlie CFS [86], although the evidence reviewed here supports the idea that more laterally situated brain stem lesions might be responsible. MRI of the highest quality is needed, followed up by more detailed SPECT scans, perhaps with the use of one of the new imaging agents for serotonin receptors [168]. Possibly magnetic resonance spectroscopy, if the spatial resolution can be sufficiently improved, might provide clues to a metabolic disorder.…”

Section: Discussionmentioning

confidence: 99%

Chronic fatigue syndrome—aetiological aspects

Dickinson

1997

Eur J Clin Investigation

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The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition there are no consistently abnormal physical signs or abnormalities on laboratory investigation. Many physicians remain convinced that the symptoms are psychological rather than physical in origin. This view is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms between CFS and depression remains a source of confusion and difficulty. But even if all CFS patients were rediagnosed as depressives, this would not negate the possibility of an underlying organic cause for the condition, in view of the growing evidence that depression itself has a physical cause and responds best to physical treatments. There is some evidence both for active viral infection and for an immunological disorder in the CFS. Many observations suggest that the syndrome could derive from residual damage to the reticular activating system (RAS) of the upper brain stem and/or to its cortical projections. Such damage could be produced by a previous viral infection, leaving functional defects unaccompanied by any gross histological changes. In animal experiments activation of the RAS can change sleep state and activate or stimulate cortical functions. RAS lesions can produce somnolence and apathy. Studies by modern imaging techniques have not been entirely consistent, but many magnetic resonance imaging (MRI) studies already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS. Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis--in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to treatment can already be envisaged.

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Section: Discussionmentioning

confidence: 99%

Chronic fatigue syndrome—aetiological aspects

Dickinson

1997

Eur J Clin Investigation

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“…While studies of SERT binding in depression have been attempted using 11 C and 18 F-labeled fluoxetine, sertraline, citalopram and paroxetine (Dannals et al, 1990; Suehiro et al, 1991; Das and Mukherjee, 1993), these agents were not suitable for imaging in humans (Scheffel et al, 1994). In contrast, the selective radioligand, [ 11 C](+)McN5652, has been used successfully to image SERT sites in humans (Suehiro et al, 1993; Szabo et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Low brain serotonin transporter binding in major depressive disorder

Newberg

Amsterdam

Wintering

et al. 2012

Psychiatry Research: Neuroimaging

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We examined midbrain, medial temporal lobe, and basal ganglia serotonin transporter (SERT) distribution volume ratio (DVR) values in subjects with major depressive disorder versus healthy volunteers using a selective SERT radioligand and single photon emission computed tomography (SPECT). We hypothesized that the DVR value for SERT binding would be lower in depressed versus non-depressed subjects. [123I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 10 drug free, healthy volunteers. The primary outcome measure was the DVR value for [123I]-ADAM uptake in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated significantly lower DVR values in the midbrain, right and left medial temporal lobe, and right and left basal ganglia. There was s significant probability that lower DVR values could distinguish between depressed and non-depressed subjects in the midbrain, medial temporal lobe, and the right and left basal ganglia. These findings confirm prior observations of lower SERT binding in depression, and suggest that low SERT binding may represent a putative biomarker of depression. Future studies are needed to confirm these observations.

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“…As the central site of action of many existing antidepressant drugs of the selective serotonin reuptake inhibitor (SSRI) type, the serotonin transporter (SERT) has been the focus of intense study for many years. − In vivo imaging of SERT in living human brain, either by positron emission tomography (PET) or by single photon emission computed tomography (SPECT), has also been pursued vigorously by many groups but has met with limited success . Most of the candidate radiotracers, while possessing high affinity for SERT in vitro, have shown poor ex vivo binding characteristics …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] In vivo imaging of SERT in living human brain, either by positron emission tomography (PET) or by single photon emission computed tomography (SPECT), has also been pursued vigorously by many groups but has met with limited success. 5 Most of the candidate radiotracers, while possessing high affinity for SERT in vitro, have shown poor ex vivo binding characteristics. 6 The most common defects have been poor signal-to-noise ratios and a lack of selectivity for SERT over other monoaminergic transporters: the dopamine transporter (DAT) and the norepinephrine transporter (NET).…”

Section: Introductionmentioning

confidence: 99%

Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of ¹¹C-Labeled 2-(Phenylthio)araalkylamines

et al. 2000

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A series of four 2-(phenylthio)araalkylamines have been radiolabeled with 11 C and evaluated as potential radiotracers for imaging the serotonin transporter (SERT) by positron emission tomography (PET). All four candidates display high affinity for SERT and low affinity for the dopamine or norepinephrine transporters using in vitro binding assays. Biodistribution studies in rats demonstrated that tail-vein injection of the 11 C-labeled radiotracers resulted in high brain uptake of radioactivity with a preferential distribution in brain regions known to be rich in SERT such as hypothalamus and thalamus. The most promising candidate, 16, had hypothalamus-to-cerebellum ratios of 9:1, 1 h postinjection, an indication of high specific to nonspecific binding. Ex vivo pharmacological studies demonstrated that uptake in SERT-rich brain regions was both saturable and selective for SERT. Two of the tested radiotracers, 15 and 16, have highly favorable properties for imaging SERT and will be used in pilot human PET imaging studies.

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Development of PET/SPECT Ligands for the Serotonin Transporter

Cited by 8 publications

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Chronic fatigue syndrome—aetiological aspects

Chronic fatigue syndrome—aetiological aspects

Low brain serotonin transporter binding in major depressive disorder

Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of ¹¹C-Labeled 2-(Phenylthio)araalkylamines

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Development of PET/SPECT Ligands for the Serotonin Transporter

Cited by 8 publications

References 0 publications

Chronic fatigue syndrome—aetiological aspects

Chronic fatigue syndrome—aetiological aspects

Low brain serotonin transporter binding in major depressive disorder

Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of 11C-Labeled 2-(Phenylthio)araalkylamines

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Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of ¹¹C-Labeled 2-(Phenylthio)araalkylamines