Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

Marner, Lisbeth; Gillings, Nic; Madsen, Karine; Erritzoe, David; Baaré, William F.C.; Svarer, Claus; Hasselbalch, Steen G.; Knudsen, Gitte M.

doi:10.1016/j.neuroimage.2010.01.054

Cited by 79 publications

(85 citation statements)

References 35 publications

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“…No sex or age effects on the 5-HT 4 receptor density have been described in the human postmortem studies (Bonaventure et al, 2000;Reynolds et al, 1995;Varnas et al, 2003). In an earlier PET study with [ 11 C]SB207145 in a smaller younger cohort, we found that 5-HT 4 receptor binding declined with age, and a post hoc analysis suggested that women have lower binding in the hippocampus than men (Marner et al, 2010). The aim of this study was to evaluate age and sex effects on 5-HT 4 receptor binding in a larger cohort of healthy subjects, also including older individuals.…”

Section: Introductionmentioning

confidence: 39%

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Madsen

Haahr

Marner

et al. 2011

J Cereb Blood Flow Metab

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Experimental studies indicate that the 5-HT 4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT 4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [ 11 C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BP ND , was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT 4 receptor binding in the limbic system. The lower limbic 5-HT 4 receptor binding in women supports a role for 5-HT 4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT 4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.

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Section: Introductionmentioning

confidence: 39%

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Madsen

Haahr

Marner

et al. 2011

J Cereb Blood Flow Metab

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“…11 C]SB207145 might not be displaceable by acute, dynamic changes in 5-HT availability (Marner et al 2009(Marner et al , 2010, the current findings point to the potential of such radioligands for detecting changes in 5-HT availability which are gradual and long-lasting.…”

Section: Discussionmentioning

confidence: 60%

“…11 C]SB207145, has recently been developed for human use (Marner et al 2009(Marner et al , 2010, thereby offering the prospect of correlating individual 5-HTT binding with that of 5-HT 4 receptors. Indeed, a recent PET study examining 5-HT 2A receptor and 5-HTT binding in parallel demonstrated a strong correlative relationship between the two , thereby adding clinical relevance to the idea that 5-HTT variation influences 5-HT receptor subtypes.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

Jennings

Licht

Bruce³

et al. 2011

Int. J. Neuropsychopharm.

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Genetic variation in 5-HT transporter (5-HTT) expression is a key risk factor for psychiatric disorder and has been linked to changes in the expression of certain 5-HT receptor subtypes. This study investigated the effect of variation in 5-HTT expression on 5-HT 4 receptor levels in both 5-HTT knockout (KO) and overexpressing (OE) mice using autoradiography with the selective 5-HT 4 receptor radioligand,

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“…Previous studies using Göttingen minipigs and 11 C-SB207145, a potent radiotracer for imaging 5HT4R in the brain, reported BP ND s in the striatum of around 2.0 (17). In humans, 11 C-SB207145 BP ND s in the striatum and hippocampus were determined to be around 2.6-4.2 and 0.8-1.1, respectively (18,27). 123 I-SB207711 BP ND s in rodents and cynomolgus monkeys were found to be approximately 2.4 and 3.0, respectively (19).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Evaluation of ¹⁸F-MNI698: An ¹⁸F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain

et al. 2014

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Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a novel therapeutic approach to multiple brain disorders, including Alzheimer and Huntington disease. In vivo imaging of these receptors with selective 5HT4R radiotracers and PET would be valuable to investigate alterations in 5HT4R in different brain disorders and to assist drug discovery. In this study, 18 F-MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the brain. Methods: Eighteen PET studies were performed in 3 adult rhesus monkeys. The radiotracer was administered as a bolus intravenous injection or bolus plus constant infusion (time that would be required to inject the bolus at the infusion rate 5 60 min), and arterial blood was collected for data quantification. Kinetic models were used to estimate distribution volumes and binding potentials, for which the cerebellum was used as a reference region. 18 F-MNI698 test-retest variability and upper mass dose limits were determined. Preblocking studies using several doses of SB204070, a selective 5HT4R antagonist, were performed. Results: 18 F-MNI698 avidly entered the monkey brain (peak percentage injected dose of ∼6.6%), and its brain distribution was consistent with known 5HT4R densities. At 120 min after bolus injection and after the start of radiotracer infusion, only less than 5% and approximately 10% parent compound was present in blood, respectively. Measured binding potentials were underestimated by 22%-36% when noninvasive methods were used for data quantification in comparison with invasive methods. A good agreement was found between test-retest measurements. The radiotracer upper mass dose limit (,5% occupancy) was determined to be 13.1 μg per 70 kg of body weight. SB204070 blocked the radiotracer binding in a dose-dependent manner. Conclusion: Data indicate that 18 F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in the brain, and human studies are warranted based on these study results.

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Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

Cited by 79 publications

References 35 publications

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

In Vivo Evaluation of ¹⁸F-MNI698: An ¹⁸F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain

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Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

Cited by 79 publications

References 35 publications

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

Genetic variation in 5-hydroxytryptamine transporter expression causes adaptive changes in 5-HT4 receptor levels

In Vivo Evaluation of 18F-MNI698: An 18F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain

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Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

In Vivo Evaluation of ¹⁸F-MNI698: An ¹⁸F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain