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Evaluation of [18 F]2FP3 in pigs and non-human primates

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Hansen, Hanne D ; Constantinescu, Cristian C ; Barret, Olivier ; Herth, Matthias M ; Magnussen, Janus H ; Lehel, Szabolcs ; Dyssegaard, Agnete ; Colomb, Julie ; Billard, Thierry ; Zimmer, Luc ; Tamagnan, Gilles ; Knudsen, Gitte M. / Evaluation of [18 F]2FP3 in pigs and non-human primates. In: Journal of Labelled Compounds and Radiopharmaceuticals. 2019 ; Vol. 62, No. 1. pp. 34-42.

Bibtex

@article{10275605925a487785e96624f585ad4e,
title = "Evaluation of [18 F]2FP3 in pigs and non-human primates",
abstract = "So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.",
keywords = "5-HT receptor, autoradiography, PET, [ F]2FP3, [ H]SB-269970",
author = "Hansen, {Hanne D} and Constantinescu, {Cristian C} and Olivier Barret and Herth, {Matthias M} and Magnussen, {Janus H} and Szabolcs Lehel and Agnete Dyssegaard and Julie Colomb and Thierry Billard and Luc Zimmer and Gilles Tamagnan and Knudsen, {Gitte M}",
note = "{\textcopyright} 2018 John Wiley & Sons, Ltd.",
year = "2019",
month = jan,
day = "1",
doi = "10.1002/jlcr.3692",
language = "English",
volume = "62",
pages = "34--42",
journal = "Journal of Labelled Compounds and Radiopharmaceuticals",
issn = "0362-4803",
publisher = "John/Wiley & Sons Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Evaluation of [18 F]2FP3 in pigs and non-human primates

AU - Hansen, Hanne D

AU - Constantinescu, Cristian C

AU - Barret, Olivier

AU - Herth, Matthias M

AU - Magnussen, Janus H

AU - Lehel, Szabolcs

AU - Dyssegaard, Agnete

AU - Colomb, Julie

AU - Billard, Thierry

AU - Zimmer, Luc

AU - Tamagnan, Gilles

AU - Knudsen, Gitte M

N1 - © 2018 John Wiley & Sons, Ltd.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.

AB - So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.

KW - 5-HT receptor

KW - autoradiography

KW - PET

KW - [ F]2FP3

KW - [ H]SB-269970

UR - http://www.scopus.com/inward/record.url?scp=85058044223&partnerID=8YFLogxK

U2 - 10.1002/jlcr.3692

DO - 10.1002/jlcr.3692

M3 - Journal article

C2 - 30414212

VL - 62

SP - 34

EP - 42

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

SN - 0362-4803

IS - 1

ER -

ID: 56614646