Characterization of the serotonin 2A receptor selective PET tracer (R)-[18F]MH.MZ in the human brain

Vasko Kramer; Agnete Dyssegaard; Jonathan Flores; Cristian Soza-Ried; Frank Rösch; Gitte Moos Knudsen; Horacio Amaral; Matthias M. Herth

doi:10.1007/s00259-019-04527-w

Characterization of the serotonin 2A receptor selective PET tracer (R)-[¹⁸F]MH.MZ in the human brain

Vasko Kramer^*, Agnete Dyssegaard, Jonathan Flores, Cristian Soza-Ried, Frank Rösch, Gitte Moos Knudsen, Horacio Amaral, Matthias M. Herth

^*Corresponding author for this work

Department of Clinical Medicine

1 Citation (Scopus)

Abstract

Purpose: The serotonin receptor subtype 2A antagonist (5-HT_2AR) (R)-[¹⁸F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT_2ARs. It displays a very similar selectivity profile as [¹¹C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT_2AR. As [¹¹C]MDL 100907, (R)-[¹⁸F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT_2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[¹⁸F]MH.MZ PET to image and quantify the 5-HT_2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[¹⁸F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[¹⁸F]MH.MZ 5-HT_2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT_2AR rich regions with a BP_ND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[¹⁸F]MH.MZ binding conformed to the known distribution of 5-HT_2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[¹⁸F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT_2AR system in humans. In comparison with [¹¹C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[¹⁸F]MH.MZ. We believe that (R)-[¹⁸F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT_2AR system.

Original language	English
Journal	European Journal of Nuclear Medicine and Molecular Imaging
ISSN	1619-7070
DOIs	https://doi.org/10.1007/s00259-019-04527-w
Publication status	Published - 1 Feb 2020

Keywords

5-HT receptor
Kinetic modeling
MDL 100907
Positron emission tomography (PET)
[F]MH.MZ

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10.1007/s00259-019-04527-w

Cite this

@article{a6ac9d3331a44017808bfb3334638a5c,

title = "Characterization of the serotonin 2A receptor selective PET tracer (R)-[18F]MH.MZ in the human brain",

abstract = "Purpose: The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.",

keywords = "5-HT receptor, Kinetic modeling, MDL 100907, Positron emission tomography (PET), [F]MH.MZ",

author = "Vasko Kramer and Agnete Dyssegaard and Jonathan Flores and Cristian Soza-Ried and Frank R{\"o}sch and Knudsen, {Gitte Moos} and Horacio Amaral and Herth, {Matthias M.}",

year = "2020",

month = feb,

day = "1",

doi = "10.1007/s00259-019-04527-w",

language = "English",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer",

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TY - JOUR

T1 - Characterization of the serotonin 2A receptor selective PET tracer (R)-[18F]MH.MZ in the human brain

AU - Kramer, Vasko

AU - Dyssegaard, Agnete

AU - Flores, Jonathan

AU - Soza-Ried, Cristian

AU - Rösch, Frank

AU - Knudsen, Gitte Moos

AU - Amaral, Horacio

AU - Herth, Matthias M.

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Purpose: The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.

AB - Purpose: The serotonin receptor subtype 2A antagonist (5-HT2AR) (R)-[18F]MH.MZ has in preclinical studies been identified as a promising PET imaging agent for quantification of cerebral 5-HT2ARs. It displays a very similar selectivity profile as [11C]MDL 100907, one of the most selective compounds identified thus far for the 5-HT2AR. As [11C]MDL 100907, (R)-[18F]MH.MZ also displays slow brain kinetics in various animal models; however, the half-life of fluorine-18 allows for long scan times and consequently, a more precise determination of 5-HT2AR binding could still be feasible. In this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ PET to image and quantify the 5-HT2AR in the human brain in vivo. Methods: Nine healthy volunteers underwent (R)-[18F]MH.MZ PET at baseline and four out of these also received a second PET scan, after ketanserin pretreatment. Regional time–activity curves of 17 brain regions were analyzed before and after pretreatment. We also investigated radiometabolism, time-dependent stability of outcomes measures, specificity of (R)-[18F]MH.MZ 5-HT2AR binding, and performance of different kinetic modeling approaches. Results: Highest uptake was determined in 5-HT2AR rich regions with a BPND of approximately 1.5 in cortex regions. No radiometabolism was observed. 1TCM and 2TCM resulted in similar outcome measure, whereas reference tissue models resulted in a small, but predictable bias. (R)-[18F]MH.MZ binding conformed to the known distribution of 5-HT2AR and could be blocked by pretreatment with ketanserin. Moreover, outcomes measures were stable after 100–110 min. Conclusion: (R)-[18F]MH.MZ is a suitable PET tracer to image and quantify the 5-HT2AR system in humans. In comparison with [11C]MDL 100907, faster and more precise outcome measure could be obtained using (R)-[18F]MH.MZ. We believe that (R)-[18F]MH.MZ has the potential to become the antagonist radiotracer of choice to investigate the human 5-HT2AR system.

KW - 5-HT receptor

KW - Kinetic modeling

KW - MDL 100907

KW - Positron emission tomography (PET)

KW - [F]MH.MZ

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U2 - 10.1007/s00259-019-04527-w

DO - 10.1007/s00259-019-04527-w

M3 - Journal article

C2 - 31606832

AN - SCOPUS:85074607537

SN - 1619-7070

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

ER -