Comparison of [18F]F-CNBI and [18F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice

Heather M. Stein; Surendra R. Gundam; Aditya Bansal; Nicholas R. Nelson; Geoffry L. Curran; Timothy R. DeGrado; Mark A. Frye; John D. Port; Val J. Lowe; Melissa E. Murray; Mukesh K. Pandey

doi:10.1002/ejoc.202201031

Comparison of [¹⁸F]F-CNBI and [¹⁸F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice

Heather M. Stein, Surendra R. Gundam, Aditya Bansal, Nicholas R. Nelson, Geoffry L. Curran, Timothy R. DeGrado, Mark A. Frye, John D. Port, Val J. Lowe, Melissa E. Murray, Mukesh K. Pandey

Research output: Contribution to journal › Article › peer-review

Abstract

Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, [¹⁸F]F-CNBI and [¹⁸F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. [¹⁹F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC₅₀=19.4±2.5 nM; n=3, for GSK-3α, IC₅₀=19.4±3.8 nM; n=3, for GSK-3β) compared to [¹⁹F]F-CNBI (IC₅₀=107.6±26.0 nM; n=4, for GSK-3α, IC₅₀=105.3±18.2 nM; n=3, for GSK-3β). [¹⁸F]F-CNPIFE showed 9.5-fold higher brain uptake than [¹⁸F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of [¹⁹F]F-CNPIFE with respect to [¹⁸F]F-CNBI. Overall, [¹⁸F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model.

Original language	English (US)
Article number	e202201031
Journal	European Journal of Organic Chemistry
Volume	26
Issue number	3
DOIs	https://doi.org/10.1002/ejoc.202201031
State	Published - Jan 17 2023

Keywords

Glycogen synthase kinase
Positron emission tomography
Radiolabeling
[F]F-CNBI
[F]F-CNPIFE

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.1002/ejoc.202201031

Cite this

Stein, H. M., Gundam, S. R., Bansal, A., Nelson, N. R., Curran, G. L., DeGrado, T. R., Frye, M. A., Port, J. D., Lowe, V. J., Murray, M. E., & Pandey, M. K. (2023). Comparison of [¹⁸F]F-CNBI and [¹⁸F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice. European Journal of Organic Chemistry, 26(3), Article e202201031. https://doi.org/10.1002/ejoc.202201031

Stein, HM, Gundam, SR, Bansal, A, Nelson, NR, Curran, GL, DeGrado, TR, Frye, MA , Port, JD , Lowe, VJ , Murray, ME & Pandey, MK 2023, 'Comparison of [¹⁸F]F-CNBI and [¹⁸F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice', European Journal of Organic Chemistry, vol. 26, no. 3, e202201031. https://doi.org/10.1002/ejoc.202201031

@article{7b8deb8a200b47e7886f9ffae949ff84,

title = "Comparison of [18F]F-CNBI and [18F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice",

abstract = "Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, [18F]F-CNBI and [18F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. [19F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC50=19.4±2.5 nM; n=3, for GSK-3α, IC50=19.4±3.8 nM; n=3, for GSK-3β) compared to [19F]F-CNBI (IC50=107.6±26.0 nM; n=4, for GSK-3α, IC50=105.3±18.2 nM; n=3, for GSK-3β). [18F]F-CNPIFE showed 9.5-fold higher brain uptake than [18F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of [19F]F-CNPIFE with respect to [18F]F-CNBI. Overall, [18F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model.",

keywords = "Glycogen synthase kinase, Positron emission tomography, Radiolabeling, [F]F-CNBI, [F]F-CNPIFE",

author = "Stein, {Heather M.} and Gundam, {Surendra R.} and Aditya Bansal and Nelson, {Nicholas R.} and Curran, {Geoffry L.} and DeGrado, {Timothy R.} and Frye, {Mark A.} and Port, {John D.} and Lowe, {Val J.} and Murray, {Melissa E.} and Pandey, {Mukesh K.}",

note = "Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2023",

month = jan,

day = "17",

doi = "10.1002/ejoc.202201031",

language = "English (US)",

volume = "26",

journal = "European Journal of Organic Chemistry",

issn = "1434-193X",

publisher = "Wiley-VCH Verlag",

number = "3",

}

TY - JOUR

T1 - Comparison of [18F]F-CNBI and [18F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice

AU - Stein, Heather M.

AU - Gundam, Surendra R.

AU - Bansal, Aditya

AU - Nelson, Nicholas R.

AU - Curran, Geoffry L.

AU - DeGrado, Timothy R.

AU - Frye, Mark A.

AU - Port, John D.

AU - Lowe, Val J.

AU - Murray, Melissa E.

AU - Pandey, Mukesh K.

PY - 2023/1/17

Y1 - 2023/1/17

N2 - Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, [18F]F-CNBI and [18F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. [19F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC50=19.4±2.5 nM; n=3, for GSK-3α, IC50=19.4±3.8 nM; n=3, for GSK-3β) compared to [19F]F-CNBI (IC50=107.6±26.0 nM; n=4, for GSK-3α, IC50=105.3±18.2 nM; n=3, for GSK-3β). [18F]F-CNPIFE showed 9.5-fold higher brain uptake than [18F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of [19F]F-CNPIFE with respect to [18F]F-CNBI. Overall, [18F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model.

AB - Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, [18F]F-CNBI and [18F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. [19F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC50=19.4±2.5 nM; n=3, for GSK-3α, IC50=19.4±3.8 nM; n=3, for GSK-3β) compared to [19F]F-CNBI (IC50=107.6±26.0 nM; n=4, for GSK-3α, IC50=105.3±18.2 nM; n=3, for GSK-3β). [18F]F-CNPIFE showed 9.5-fold higher brain uptake than [18F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of [19F]F-CNPIFE with respect to [18F]F-CNBI. Overall, [18F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model.

KW - Glycogen synthase kinase

KW - Positron emission tomography

KW - Radiolabeling

KW - [F]F-CNBI

KW - [F]F-CNPIFE

UR - http://www.scopus.com/inward/record.url?scp=85144964291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85144964291&partnerID=8YFLogxK

U2 - 10.1002/ejoc.202201031

DO - 10.1002/ejoc.202201031

M3 - Article

AN - SCOPUS:85144964291

SN - 1434-193X

VL - 26

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 3

M1 - e202201031

ER -