Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective agonist [(11)C]E-55888

Hanne D Hansen; Valdemar Lykke Andersen; Szabolcs Lehel; Janus H. Magnussen; Agnete Dyssegaard; Nikolas Stroth; Jesper L Kristensen; Gitte M Knudsen; Matthias M Herth

doi:10.1016/j.bmcl.2015.03.039

Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective agonist [(11)C]E-55888

Hanne D Hansen, Valdemar Lykke Andersen, Szabolcs Lehel, Janus H. Magnussen, Agnete Dyssegaard, Nikolas Stroth, Jesper L Kristensen, Gitte M Knudsen, Matthias M Herth

12 Citationer (Scopus)

Abstract

E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging. [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60 °C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo.

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	25
Udgave nummer	9
Sider (fra-til)	1901-4
Antal sider	4
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2015.03.039
Status	Udgivet - 1 maj 2015

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title = "Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective agonist [(11)C]E-55888",

abstract = "E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging. [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60 °C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo.",

author = "Hansen, \{Hanne D\} and \{Lykke Andersen\}, Valdemar and Szabolcs Lehel and Magnussen, \{Janus H.\} and Agnete Dyssegaard and Nikolas Stroth and Kristensen, \{Jesper L\} and Knudsen, \{Gitte M\} and Herth, \{Matthias M\}",

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doi = "10.1016/j.bmcl.2015.03.039",

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AU - Hansen, Hanne D

AU - Lykke Andersen, Valdemar

AU - Lehel, Szabolcs

AU - Magnussen, Janus H.

AU - Dyssegaard, Agnete

AU - Stroth, Nikolas

AU - Kristensen, Jesper L

AU - Knudsen, Gitte M

AU - Herth, Matthias M

PY - 2015/5/1

Y1 - 2015/5/1

N2 - E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging. [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60 °C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo.

AB - E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging. [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60 °C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo.

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DO - 10.1016/j.bmcl.2015.03.039

M3 - Journal article

C2 - 25857944

SN - 0960-894X

VL - 25

SP - 1901

EP - 1904

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 9

ER -

Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective agonist [(11)C]E-55888

Abstract

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