Labeling and preliminary in vivo evaluation of the 5-HT7 receptor selective agonist [(11)C]E-55888

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

doi:10.1016/j.bmcl.2015.03.039

Labeling and preliminary in vivo evaluation of the 5-HT7 receptor selective agonist [(11)C]E-55888

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

8 Citations (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 1.7-2.4GBq. 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.

Original language	English
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	25
Issue number	9
Pages (from-to)	1901-4
Number of pages	4
ISSN	0960-894X
DOIs	https://doi.org/10.1016/j.bmcl.2015.03.039
Publication status	Published - 1 May 2015

Access to Document

10.1016/j.bmcl.2015.03.039

Cite this

@article{55a9283309624acf8e55481785669231,

title = "Labeling and preliminary in vivo evaluation of the 5-HT7 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 1.7-2.4GBq. 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 Andersen, {Valdemar L} and Szabolcs Lehel and Magnussen, {Janus H} and Agnete Dyssegaard and Nikolas Stroth and Kristensen, {Jesper Langgaard} and Knudsen, {Gitte M} and Herth, {Matthias M}",

year = "2015",

month = may,

day = "1",

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

language = "English",

volume = "25",

pages = "1901--4",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Pergamon Press",

number = "9",

}

TY - JOUR

T1 - Labeling and preliminary in vivo evaluation of the 5-HT7 receptor selective agonist [(11)C]E-55888

AU - Hansen, Hanne D

AU - Andersen, Valdemar L

AU - Lehel, Szabolcs

AU - Magnussen, Janus H

AU - Dyssegaard, Agnete

AU - Stroth, Nikolas

AU - Kristensen, Jesper Langgaard

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 1.7-2.4GBq. 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 1.7-2.4GBq. 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.

U2 - 10.1016/j.bmcl.2015.03.039

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-HT7 receptor selective agonist [(11)C]E-55888

Abstract

Access to Document

Fingerprint

Cite this