Mass dose effects and in vivo affinity in brain PET receptor studies — a study of cerebral 5-HT4 receptor binding with [11C]SB207145

Madsen, Karine; Marner, Lisbeth; Haahr, Mette E.; Gillings, Nic; Knudsen, Gitte M.

doi:10.1016/j.nucmedbio.2011.04.006

Cited by 49 publications

(42 citation statements)

References 25 publications

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“…An intravenous bolus injection of [ 11 C]SB207145 (injected radioactivity: mean± s.d.=508± 133 MBq, range=206-617 MBq) was given over 20 s. Immediately following injection, a 2-hour dynamic emission scan including 38 time frames (6×5, 10×15, 4×30, 5×120, 5×300, and 8×600 s) was acquired using one of two scanners: 1) an eighteen-ring GE-Advance scanner (GE, Milwaukee, WI) operating in 3D-acquisition mode with an approximate in-plane resolution of 6 mm or 2) a Siemens ECAT HRRT scanner operating in 3D-acquisition mode with an approximate inplane resolution of 2 mm. The injected mass given (average=2.06± 1.65 μg; range=0.14-5.91 μg) was within previously established tracer dose limits for this compound (Madsen et al, 2011b). Dynamic PET images acquired on the GE-Advance scanner were reconstructed using filtered back projection and corrected for attenuation, dead-time and scatter.…”

Section: Magnetic Resonance Imaging Data Acquisitionmentioning

confidence: 93%

“…Exclusion criteria for all participants included 1) primary psychiatric disease, 2) substance or drug abuse and 3) severe systemic or neurological disease based on history and physical/neurological examination. Thirty datasets included in the current study have been included in studies published previously (Madsen et al, 2011a(Madsen et al, ,2011bMarner et al, 2009Marner et al, , 2010.…”

Section: Participantsmentioning

confidence: 99%

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5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

et al. 2012

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Section: Magnetic Resonance Imaging Data Acquisitionmentioning

confidence: 93%

Section: Participantsmentioning

confidence: 99%

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

et al. 2012

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“…Arterial blood samples were collected each 45 s until 6 min after injection and then at 8,10,15,20,25,30,45,60,90, and 120 min. With the exception of the samples collected for metabolite analysis (3.5 mL each), all blood samples were 1 mL each.…”

Section: Pet Studiesmentioning

confidence: 99%

“…The methodology used to estimate the radiotracer ID 50 and to calculate the upper mass dose limits that will result in 5% or 10% receptor occupancy (D 5 or D 10 , respectively) was based on previously published literature (supplemental materials) (25).…”

Section: Pet Studiesmentioning

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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“…Scans were reconstructed using the iterative point-spread function reconstruction with attenuation map improvements (Sureau et al, 2008). All doses were below the recommended limits, ensuring tracer conditions (Madsen et al, 2011). …”

Section: Pet Data Acquisitionmentioning

confidence: 99%

Fluctuations in [11C]SB207145 PET Binding Associated with Change in Threat-Related Amygdala Reactivity in Humans

Fisher

Haahr

Jensen

et al. 2015

Neuropsychopharmacol

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Serotonin critically affects the neural processing of emotionally salient stimuli, including indices of threat; however, how alterations in serotonin signaling contribute to changes in brain function is not well understood. Recently, we showed in a placebo-controlled study of 32 healthy males that brain serotonin 4 receptor (5-HT4) binding, assessed with [(11)C]SB207145 PET, was sensitive to a 3-week intervention with the selective serotonin reuptake inhibitor fluoxetine, supporting it as an in vivo model for fluctuations in central serotonin levels. Participants also underwent functional magnetic resonance imaging while performing a gender discrimination task of fearful, angry, and neutral faces. This offered a unique opportunity to evaluate whether individual fluctuations in central serotonin levels, indexed by change in [(11)C]SB207145 binding, predicted changes in threat-related reactivity (ie, fear and angry vs neutral faces) within a corticolimbic circuit including the amygdala and medial prefrontal and anterior cingulate cortex. We observed a significant association such that decreased brain-wide [(11)C]SB207145 binding (ie, increased brain serotonin levels) was associated with lower threat-related amygdala reactivity, whereas intervention group status did not predict change in corticolimbic reactivity. This suggests that in the healthy brain, interindividual responses to pharmacologically induced and spontaneously occurring fluctuations in [(11)C]SB207145 binding, a putative marker of brain serotonin levels, affect amygdala reactivity to threat. Our finding also supports that change in brain [(11)C]SB207145 binding may be a relevant marker for evaluating neurobiological mechanisms underlying sensitivity to threat and serotonin signaling.

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Mass dose effects and in vivo affinity in brain PET receptor studies — a study of cerebral 5-HT4 receptor binding with [11C]SB207145

Cited by 49 publications

References 25 publications

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

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

Fluctuations in [11C]SB207145 PET Binding Associated with Change in Threat-Related Amygdala Reactivity in Humans

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Mass dose effects and in vivo affinity in brain PET receptor studies — a study of cerebral 5-HT4 receptor binding with [11C]SB207145

Cited by 49 publications

References 25 publications

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

5-HTTLPR status predictive of neocortical 5-HT4 binding assessed with [11C]SB207145 PET in humans

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

Fluctuations in [11C]SB207145 PET Binding Associated with Change in Threat-Related Amygdala Reactivity in Humans

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