Noradrenaline transporter availability on [11C]MRB PET predicts weight loss success in highly obese adults

Vettermann, Franziska; Rullmann, Michael; Becker, Georg; Luthardt, Julia; Zientek, Franziska; Patt, Marianne; Meyer, Philipp; McLeod, Anke; Brendel, Matthias; Blüher, Matthias; Stümvoll, Michael; Hilbert, Anja; Ding, Yu‐Shin; Sabri, Osama; Hesse, Swen

doi:10.1007/s00259-018-4002-7

Cited by 7 publications

(29 citation statements)

References 43 publications

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“…Consequently, the researchers using 11 C-MRB PET have come to mutual conclusions that the NET availability in the thalamus region of obese adults is decreased when compared to healthy controls (Li et al 2014;Bresch et al 2017). In addition, by measuring the CNS NET availability, it is possible to predict the result of a dietary intervention, and is helpful for adjusting treatment options of highly obese adults (Vettermann et al 2018). BAT plays a role in energy balance and is also regulated by the SNS.…”

Section: C-mrbmentioning

confidence: 99%

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

et al. 2020

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The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used 123/131 I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. 11 C-HED and 18 F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed.

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Section: C-mrbmentioning

confidence: 99%

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

et al. 2020

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“…Despite being the most effective treatment for severe obesity, the understanding of how RYGB affects central neurotransmission, specifically the function of brain monoamines, is still at its beginning. Own previous study using PET and the NAT-selective radiotracer [ 11 C]MRB indicated that NAT availability is a marker of the integrity of the LC-NA system, and that its tone is altered in relation to changes in BMI and BW [16,18,24]. Based on these data, we hypothesized that NAT availability changes 6 months after RYGB surgery in relation to changes in BMI.…”

Section: Discussionmentioning

confidence: 95%

“…A direct relationship, however, between the NA system and changes in body weight (BW) following surgical intervention, i.e., RYGB, has not yet been explored. Based on own previous studies with dietary intervention and a normal weight control group [16,17] and a study by Li et al [18], our general assumption is that NAT availability as a marker of the central noradrenergic tone significantly decreases with reduction in BMI from severe (BMI > 35 kg/ m 2 ) to moderate obesity (BMI 30-35 kg/m 2 ) but increases with reduction from moderate obesity to normal body weight (BMI 18.5-25 kg/m 2 ) describing a U-shaped curve, specifically in the hypothalamus, the insula, and the prefrontal brain area.…”

Section: Introductionmentioning

confidence: 99%

Central Noradrenergic Neurotransmission and Weight Loss 6 Months After Gastric Bypass Surgery in Patients with Severe Obesity

et al. 2021

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Purpose Roux-en-Y gastric bypass (RYGB) surgery is currently the most efficient treatment to achieve long-term weight loss in individuals with severe obesity. This is largely attributed to marked reductions in food intake mediated in part by changes in gut-brain communication. Here, we investigated for the first time whether weight loss after RYGB is associated with alterations in central noradrenaline (NA) neurotransmission. Materials and Methods We longitudinally studied 10 individuals with severe obesity (8 females; age 43.9 ± 13.1 years; body mass index (BMI) 46.5 ± 4.8 kg/m2) using (S,S)-[11C]O-methylreboxetine and positron emission tomography to estimate NA transporter (NAT) availability before and 6 months after surgery. NAT distribution volume ratios (DVR) were calculated by volume-of-interest analysis and the two-parameter multilinear reference tissue model (reference region: occipital cortex). Results The participants responded to RYGB surgery with a reduction in BMI of 12.0 ± 3.5 kg/m2 (p < 0.001) from baseline. This was paralleled by a significant reduction in DVR in the dorsolateral prefrontal cortex (pre-surgery 1.12 ± 0.04 vs. post-surgery 1.07 ± 0.04; p = 0.019) and a general tendency towards reduced DVR throughout the brain. Furthermore, we found a strong positive correlation between pre-surgery DVR in hypothalamus and the change in BMI (r = 0.78; p = 0.01). Conclusion Reductions in BMI after RYGB surgery are associated with NAT availability in brain regions responsible for decision-making and homeostasis. However, these results need further validation in larger cohorts, to assess whether brain NAT availability could prognosticate the outcome of RYGB on BMI. Graphical abstract

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“…The potential implication of changes in the dopaminergic system has been broadly discussed and is reviewed in this special issue [ 2 , 3 ]. The specific role of the other central biogenic amines, i.e., serotonin (5-hydroxytryp-tamine, 5-HT) and noradrenaline (NA), in the pathogenesis of overweight and obesity have, however, been relatively less well explored [ 2 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, carbon-11-labeled methylreboxetine ([ 11 C]MRB) is the clinically most applied radiotracer to visualize and quantify NAT availability in vivo in order to assess whether changes of NA/NAT are associated with excessive weight gain and obesity. Our own previous research on the relationship between NAT availability and BMI indicated a rather reciprocal relationship in the hypothalamus with the lowest BP ND in individuals with modest to high BMI [ 5 , 6 , 7 , 8 ]. Diminished hypothalamic NAT availability in overweight and obesity and an impaired turnover of NA could explain the associated hyperphagia.…”

Section: Introductionmentioning

confidence: 99%

Central Serotonin/Noradrenaline Transporter Availability and Treatment Success in Patients with Obesity

et al. 2022

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Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.

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Noradrenaline transporter availability on [11C]MRB PET predicts weight loss success in highly obese adults

Cited by 7 publications

References 43 publications

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

Central Noradrenergic Neurotransmission and Weight Loss 6 Months After Gastric Bypass Surgery in Patients with Severe Obesity

Central Serotonin/Noradrenaline Transporter Availability and Treatment Success in Patients with Obesity

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