Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

Borgers, Anke J; Alkemade, Anneke; Giessen, Elsmarieke van de; Drent, Madeleine L.; Booij, Jan; Bisschop, Peter H.; Fliers, Eric

doi:10.1186/2191-219x-3-34

Cited by 15 publications

(15 citation statements)

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“…In the hypothalamus, SERT has been shown to be ubiquitously present in controls in a postmortem human brain study (30). In line with this, PET studies using selective SERT tracers as well as an 123 I-FP-CIT SPECT study have shown specific hypothalamic binding in healthy controls (31,32). Moreover, 123 I-FP-CIT binding in the hypothalamus of rats could be blocked with an SSRI, but not with a DAT blocker (5).…”

Section: Discussionsupporting

confidence: 51%

Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

et al. 2016

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and 7 GE Healthcare, The Grove Centre, Amersham, United Kingdom 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) SPECT can visualize and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, 123 I-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. On the basis of previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson disease (PD), we hypothesized that, in addition to striatal DAT binding, there would be differences in extrastriatal 123 I-FP-CIT SPECT binding to SERT between MSA, PSP, and PD. Methods: We included patients with parkinsonian type MSA (multiple-system atrophy with predominantly parkinsonism [MSA-P], n 5 9), cerebellar type MSA (MSA-C, n 5 7), PSP (n 5 13), and PD (n 5 30). 123 I-FP-CIT binding was analyzed using region-of-interest (ROI)-as well as voxel-based methods in both the DAT-rich striatum (caudate nucleus and putamen) and the SERT-rich extrastriatal brain regions (thalamus, hypothalamus, and pons). For SERT analysis, patients on selective serotonin reuptake inhibitor were excluded (n 5 48 remained). Results: In the ROI analyses, extrastriatal 123 I-FP-CIT binding ratios in the hypothalamus were significantly lower in PSP than in MSA-C patients, and we observed significantly lower striatal 123 I-FP-CIT binding ratios in the caudate nucleus of PSP patients than in that of both PD and MSA-C patients. In the posterior putamen, binding ratios were significantly lower in MSA-P, PSP, and PD than MSA-C patients. Striatal ROI outcomes were confirmed by the voxel-based analyses that additionally showed a significantly lower hypothalamic binding in PSP and MSA-P than PD. Conclusion: Striatal 123 I-FP-CIT binding to DAT and hypothalamic 123 I-FP-CIT binding to SERT are significantly lower in MSA-P and PSP than in PD and MSA-C patients and might therefore be of interest for differential diagnosis.

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Section: Discussionsupporting

confidence: 51%

Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

et al. 2016

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“…In a second analysis, SERT binding in the hypothalamus was assessed using manually drawn ROIs on individual MRIs as described previously [22]. We used these manually drawn ROIs because it is not possible to identify the hypothalamus on SPECT images due to the limited spatial resolution.…”

Section: Methodsmentioning

confidence: 99%

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Versteeg

Koopman²,

Booij

et al. 2016

Neuroendocrinology

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Background: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. Methods: We performed a case-control study in insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using ¹²³I- FP-CIT single-photon emission computed tomography. We assessed insulin sensitivity using the homeostatic model assessment of insulin resistance. Results: BMI did not differ between the IRO and ISO subjects. SERT binding in the diencephalon was significantly lower in IRO than in ISO subjects, but was not different between lean and obese subjects. SERT binding in the hypothalamus tended to be reduced in obese versus lean subjects, but was not different between IRO and ISO subjects. Striatal DAT binding was similar between lean and obese subjects as well as between ISO and IRO subjects. Conclusions: We conclude that SERT binding in the diencephalon is reduced in insulin-resistant subjects independently of body weight, while hypothalamic SERT binding tends to be lower in obesity, with no difference between insulin-resistant and insulin-sensitive subjects. This suggests that the metabolic perturbations associated with obesity independently affect SERT binding within the diencephalon.

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“…Increasing or decreasing serotonin signalling affects heat or cold tolerance [10,11], peristalsis [9], urine storage [12,13], and blood pressure [14]. In rodents, stimulating serotonergic neurons in the hypothalamus alters energy metabolism and cardiovascular functioning [15,16]. Dopamine has also been found to play a role in the ANS [17].…”

Section: Introductionmentioning

confidence: 99%

Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies

et al. 2020

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Autonomic dysfunction is a common non-motor symptom in Parkinson's disease (PD). Dopamine and serotonin are known to play a role in autonomic regulation, and, therefore, PD-related degeneration of serotonergic and dopaminergic neurons in these regions may be associated with autonomic dysfunction. We sought to clarify the association between extrastriatal serotonergic and striatal dopaminergic degeneration and the severity of autonomic symptoms, including gastrointestinal, pupillomotor, thermoregulatory, cardiovascular, and urinary dysfunction. We performed hierarchical multiple regression analyses to determine the relationships between (extra)striatal serotonergic and dopaminergic degeneration and autonomic dysfunction in 310 patients with PD. We used [ 123 I]FP-CIT SPECT binding to presynaptic serotonin (SERT) and dopamine (DAT) transporters as a measure of the integrity of these neurotransmitter systems, and the SCOPA-AUT (Scales for Outcomes in Parkinson's Disease-Autonomic) questionnaire to evaluate the perceived severity of autonomic dysfunction. Motor symptom severity, medication status, and sex were added to the model as covariates. Additional analyses were also performed using five subdomains of the SCOPA-AUT: cardiovascular, gastrointestinal, urinary, thermoregulatory, and pupillomotor symptoms. We found that autonomic symptoms were most significantly related to lower [ 123 I]FP-CIT binding ratios in the right caudate nucleus and were mainly driven by gastrointestinal and cardiovascular dysfunction. These results provide a first look into the modest role of dopaminergic projections towards the caudate nucleus in the pathophysiology of autonomic dysfunction in PD, but the underlying mechanism warrants further investigation.

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Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

Cited by 15 publications

References 50 publications

Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies

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Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

Cited by 15 publications

References 50 publications

Analysis of Extrastriatal 123I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

Analysis of Extrastriatal 123I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Autonomic failure in Parkinson’s disease is associated with striatal dopamine deficiencies

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Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

Analysis of Extrastriatal ¹²³I-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases