PET Tracers for Serotonin Receptors and Their Applications

Js, Kumar; Mann, J. John

doi:10.2174/1871524914666141030124316

Cited by 45 publications

(33 citation statements)

References 165 publications

(196 reference statements)

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“…In the central nervous system (CNS), 5-HT2AR are abundant in cortical and forebrain areas, whereas comparatively lower density is found in hippocampus; the least expression has been detected in striatum and cerebellum (9)(10)(11)(12)(13)(14)(15)(16). Positron emission tomography (PET) imaging enables quantification of 5-HT2AR and measurement of receptor occupancy by therapeutic drug candidates in vivo (17)(18).…”

Section: Introductionmentioning

confidence: 99%

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates

et al. 2019

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Purpose: 5-HT2AR exists in high and low affinity states. Agonist PET tracers measure binding to the active high affinity site and thus provide a functionally relevant measure of the receptor. Limited in vivo data have been reported so far for a comparison of agonist versus antagonist tracers for 5-HT2AR used as a proof of principle for measurement of high and low affinity states of this receptor. We compared the in vivo binding of [11C]CIMBI-5, a 5-HT2AR agonist, and of the antagonist [11C]M100907, in monkeys and baboons. Methods: [11C]CIMBI-5 and [11C]M100907 baseline PET scans were performed in anesthetized male baboons (n=2) and male vervet monkeys (n=2) with an ECAT EXACT HR+ and GE 64-slice PET/CT Discovery VCT scanners. Blocking studies were performed in vervet monkeys by pretreatment with MDL100907 (0.5 mg/kg, i.v.) 60 minutes prior to the scan. Regional distribution volumes and binding potentials were calculated for each ROI using the likelihood estimation in graphical analysis and Logan plot, with either plasma input function or reference region as input, and simplified reference tissue model approaches. Results: PET imaging of [11C]CIMBI-5 in baboons and monkeys showed the highest binding in 5-HT2AR-rich cortical regions, while the lowest binding was observed in cerebellum, consistent with the expected distribution of 5-HT2AR. Very low free fractions and rapid metabolism were observed for [11C]CIMBI-5 in baboon plasma. Binding potential values for [11C]CIMBI-5 were 25-33% lower than those for [11C]MDL100907 in the considered brain regions. Conclusion: The lower binding potential of [11C]CIMBI-5 in comparison to [11C]MDL100907 is likely due to the preferential binding of the former to the high affinity site in vivo in contrast to the antagonist, [11C]MDL100907, which binds to both high and low affinity sites.

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Section: Introductionmentioning

confidence: 99%

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates

et al. 2019

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“…The antagonist PET ligands developed so far are not proven successful for the quantification of high affinity confirmation of 5-HT 2A Rs. 12–14 [ 11 F]CIMBI-5 and [ 11 F]CIMBI-36, analogues of dimethoxyphenylethan-1-amine, are the two 5-HT 2A/2C agonist radiotracers tested in vivo in pigs and baboons. 15–20 So far, and only [ 11 F]CIMBI-36 is currently being investigated in human.…”

mentioning

confidence: 99%

In vivo evaluation of [ 18 F]FECIMBI-36, an agonist 5-HT 2A/2C receptor PET radioligand in nonhuman primate

Prabhakaran

Sai

Zanderigo

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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We recently reported the radiosynthesis and in vitro evaluation of [18F]-2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-(2-fluoroethoxy)benzyl)ethanamine, ([18F]FECIMBI-36) or ([18F]1), an agonist radioligand for 5HT2A/2C receptors in postmortem samples of human brain. Herein we describe the in vivo evaluation of [18F]FECIMBI-36 in vervet /African green monkeys by PET imaging. PET images show that [18F]FECIMBI-36 penetrates the blood-brain barrier and a low retention of radioactivity is observed in monkey brain. Although the time activity curves indicate a somehow heterogeneous distribution of the radioligand in the brain, the low level of [18F]FECIMBI-36 in brain may limit the use of this tracer for quantification of 5-HT2A/2C receptors by PET.

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“…subtypes in these diseases, intense research has been conducted during the last few years to develop selective radioligands of interest for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging [2,3]. Among those receptors, 5-HT4R are of particular interest.…”

mentioning

confidence: 99%

Synthesis and evaluation of novel serotonin 4 receptor radiotracers for single photon emission computed tomography

Lalut

Tournier

Cailly

et al. 2016

European Journal of Medicinal Chemistry

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Despite its implication in several physiological and pathological processes the serotonin subtype-4 receptor (5-HT4R) has seen limited effort for the development of radiolabeling agent especially concerning single photon emission computed tomography (SPECT). Bearing an ester function, the available ligands are rapidly susceptible to hydrolysis which limits their use in vivo. In this study the synthesis of iodinated benzamide and ketone analogs were described. Their affinity for the 5-HT4R and their lipophilicity were evaluated and the most promising derivatives were evaluated ex vivo for their binding to the receptor and for their ability to displace the reference ligand [(125)I]-SB207710.

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PET Tracers for Serotonin Receptors and Their Applications

Cited by 45 publications

References 165 publications

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates

In vivo PET Imaging of [11C]CIMBI-5, a 5-HT2AR Agonist Radiotracer in Nonhuman Primates

In vivo evaluation of [ 18 F]FECIMBI-36, an agonist 5-HT 2A/2C receptor PET radioligand in nonhuman primate

Synthesis and evaluation of novel serotonin 4 receptor radiotracers for single photon emission computed tomography

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