In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors

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Standard

In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors. / Donat, Cornelius K.; Hansen, Henrik H.; Hansen, Hanne D.; Mease, Ronnie C.; Horti, Andrew G.; Pomper, Martin G.; L’Estrade, Elina T.; Herth, Matthias M.; Peters, Dan; Knudsen, Gitte M.; Mikkelsen, Jens D.

In: Molecules, Vol. 25, No. 6, 1425, 01.01.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Donat, CK, Hansen, HH, Hansen, HD, Mease, RC, Horti, AG, Pomper, MG, L’Estrade, ET, Herth, MM, Peters, D, Knudsen, GM & Mikkelsen, JD 2020, 'In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors', Molecules, vol. 25, no. 6, 1425. https://doi.org/10.3390/molecules25061425

APA

Donat, C. K., Hansen, H. H., Hansen, H. D., Mease, R. C., Horti, A. G., Pomper, M. G., L’Estrade, E. T., Herth, M. M., Peters, D., Knudsen, G. M., & Mikkelsen, J. D. (2020). In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors. Molecules, 25(6), [1425]. https://doi.org/10.3390/molecules25061425

Vancouver

Donat CK, Hansen HH, Hansen HD, Mease RC, Horti AG, Pomper MG et al. In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors. Molecules. 2020 Jan 1;25(6). 1425. https://doi.org/10.3390/molecules25061425

Author

Donat, Cornelius K. ; Hansen, Henrik H. ; Hansen, Hanne D. ; Mease, Ronnie C. ; Horti, Andrew G. ; Pomper, Martin G. ; L’Estrade, Elina T. ; Herth, Matthias M. ; Peters, Dan ; Knudsen, Gitte M. ; Mikkelsen, Jens D. / In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors. In: Molecules. 2020 ; Vol. 25, No. 6.

Bibtex

@article{064650bb8d5f4e2082d41e0ddfd2b231,
title = "In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors",
abstract = "The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in several cognitive and physiologic processes; its expression levels and patterns change in neurologic and psychiatric diseases, such as schizophrenia and Alzheimer{\textquoteright}s disease, which makes it a relevant drug target. Development of selective radioligands is important for defining binding properties and occupancy of novel molecules targeting the receptor. We tested the in vitro binding properties of [125I]Iodo-ASEM [(3-(1,4-diazabycyclo[3.2.2]nonan-4-yl)-6-(125I-iododibenzo[b,d]thiopentene 5,5-dioxide)] in the mouse, rat and pig brain using autoradiography. The in vivo binding properties of [18F]ASEM were investigated using positron emission tomography (PET) in the pig brain. [125I]Iodo-ASEM showed specific and displaceable high affinity (~1 nM) binding in mouse, rat, and pig brain. Binding pattern overlapped with [125I]α-bungarotoxin, specific binding was absent in α7 nAChR gene-deficient mice and binding was blocked by a range of α7 nAChR orthosteric modulators in an affinity-dependent order in the pig brain. Interestingly, relative to the wild-type, binding in β2 nAChR gene-deficient mice was lower for [125I]Iodo-ASEM (58% ± 2.7%) than [125I]α-bungarotoxin (23% ± 0.2%), potentially indicating different binding properties to heteromeric α7β2 nAChR. [18F]ASEM PET in the pig showed high brain uptake and reversible tracer kinetics with a similar spatial distribution as previously reported for α7 nAChR. Blocking with SSR-180,711 resulted in a significant decrease in [18F]ASEM binding. Our findings indicate that [125I]Iodo-ASEM allows sensitive and selective imaging of α7 nAChR in vitro, with better signal-to-noise ratio than previous tracers. Preliminary data of [18F]ASEM in the pig brain demonstrated principal suitable kinetic properties for in vivo quantification of α7 nAChR, comparable to previously published data.",
keywords = "Alpha 7, Autoradiography, NAChR, Nicotinic acetylcholine receptors, PET",
author = "Donat, {Cornelius K.} and Hansen, {Henrik H.} and Hansen, {Hanne D.} and Mease, {Ronnie C.} and Horti, {Andrew G.} and Pomper, {Martin G.} and L{\textquoteright}Estrade, {Elina T.} and Herth, {Matthias M.} and Dan Peters and Knudsen, {Gitte M.} and Mikkelsen, {Jens D.}",
year = "2020",
month = jan,
day = "1",
doi = "10.3390/molecules25061425",
language = "English",
volume = "25",
journal = "Molecules (Print Archive Edition)",
issn = "1431-5157",
publisher = "M D P I AG",
number = "6",

}

RIS

TY - JOUR

T1 - In vitro and in vivo characterization of dibenzothiophene derivatives [125I]iodo-ASEM and [18F]ASEM as radiotracers of homo- And heteromeric α7 nicotinic acetylcholine receptors

AU - Donat, Cornelius K.

AU - Hansen, Henrik H.

AU - Hansen, Hanne D.

AU - Mease, Ronnie C.

AU - Horti, Andrew G.

AU - Pomper, Martin G.

AU - L’Estrade, Elina T.

AU - Herth, Matthias M.

AU - Peters, Dan

AU - Knudsen, Gitte M.

AU - Mikkelsen, Jens D.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in several cognitive and physiologic processes; its expression levels and patterns change in neurologic and psychiatric diseases, such as schizophrenia and Alzheimer’s disease, which makes it a relevant drug target. Development of selective radioligands is important for defining binding properties and occupancy of novel molecules targeting the receptor. We tested the in vitro binding properties of [125I]Iodo-ASEM [(3-(1,4-diazabycyclo[3.2.2]nonan-4-yl)-6-(125I-iododibenzo[b,d]thiopentene 5,5-dioxide)] in the mouse, rat and pig brain using autoradiography. The in vivo binding properties of [18F]ASEM were investigated using positron emission tomography (PET) in the pig brain. [125I]Iodo-ASEM showed specific and displaceable high affinity (~1 nM) binding in mouse, rat, and pig brain. Binding pattern overlapped with [125I]α-bungarotoxin, specific binding was absent in α7 nAChR gene-deficient mice and binding was blocked by a range of α7 nAChR orthosteric modulators in an affinity-dependent order in the pig brain. Interestingly, relative to the wild-type, binding in β2 nAChR gene-deficient mice was lower for [125I]Iodo-ASEM (58% ± 2.7%) than [125I]α-bungarotoxin (23% ± 0.2%), potentially indicating different binding properties to heteromeric α7β2 nAChR. [18F]ASEM PET in the pig showed high brain uptake and reversible tracer kinetics with a similar spatial distribution as previously reported for α7 nAChR. Blocking with SSR-180,711 resulted in a significant decrease in [18F]ASEM binding. Our findings indicate that [125I]Iodo-ASEM allows sensitive and selective imaging of α7 nAChR in vitro, with better signal-to-noise ratio than previous tracers. Preliminary data of [18F]ASEM in the pig brain demonstrated principal suitable kinetic properties for in vivo quantification of α7 nAChR, comparable to previously published data.

AB - The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in several cognitive and physiologic processes; its expression levels and patterns change in neurologic and psychiatric diseases, such as schizophrenia and Alzheimer’s disease, which makes it a relevant drug target. Development of selective radioligands is important for defining binding properties and occupancy of novel molecules targeting the receptor. We tested the in vitro binding properties of [125I]Iodo-ASEM [(3-(1,4-diazabycyclo[3.2.2]nonan-4-yl)-6-(125I-iododibenzo[b,d]thiopentene 5,5-dioxide)] in the mouse, rat and pig brain using autoradiography. The in vivo binding properties of [18F]ASEM were investigated using positron emission tomography (PET) in the pig brain. [125I]Iodo-ASEM showed specific and displaceable high affinity (~1 nM) binding in mouse, rat, and pig brain. Binding pattern overlapped with [125I]α-bungarotoxin, specific binding was absent in α7 nAChR gene-deficient mice and binding was blocked by a range of α7 nAChR orthosteric modulators in an affinity-dependent order in the pig brain. Interestingly, relative to the wild-type, binding in β2 nAChR gene-deficient mice was lower for [125I]Iodo-ASEM (58% ± 2.7%) than [125I]α-bungarotoxin (23% ± 0.2%), potentially indicating different binding properties to heteromeric α7β2 nAChR. [18F]ASEM PET in the pig showed high brain uptake and reversible tracer kinetics with a similar spatial distribution as previously reported for α7 nAChR. Blocking with SSR-180,711 resulted in a significant decrease in [18F]ASEM binding. Our findings indicate that [125I]Iodo-ASEM allows sensitive and selective imaging of α7 nAChR in vitro, with better signal-to-noise ratio than previous tracers. Preliminary data of [18F]ASEM in the pig brain demonstrated principal suitable kinetic properties for in vivo quantification of α7 nAChR, comparable to previously published data.

KW - Alpha 7

KW - Autoradiography

KW - NAChR

KW - Nicotinic acetylcholine receptors

KW - PET

U2 - 10.3390/molecules25061425

DO - 10.3390/molecules25061425

M3 - Journal article

C2 - 32245032

AN - SCOPUS:85082034504

VL - 25

JO - Molecules (Print Archive Edition)

JF - Molecules (Print Archive Edition)

SN - 1431-5157

IS - 6

M1 - 1425

ER -

ID: 240942537