GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2

Sjoukje van der Hoek; Inês F Antunes; Khaled A Attia; Olivier Jacquet; Andre Heeres; Marian Bulthuis; Rolf Zijlma; Hendrikus H Boersma; Harry van Goor; Ton J Visser; Hiddo J L Heerspink; Philip H Elsinga; Jasper Stevens

doi:10.1021/acs.jmedchem.1c01269

GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2

Sjoukje van der Hoek, Inês F Antunes, Khaled A Attia, Olivier Jacquet, Andre Heeres, Marian Bulthuis, Rolf Zijlma, Hendrikus H Boersma, Harry van Goor, Ton J Visser, Hiddo J L Heerspink, Philip H Elsinga, Jasper Stevens^*

^*Corresponding author for this work

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

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Abstract

Inhibition of the sodium-glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [18F]canagliflozin was developed via a Cu-mediated 18F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [18F]canagliflozin with a yield of 0.5-3% (n = 4) and a purity of >95%. Autoradiography showed [18F]canagliflozin binding in human kidney sections containing SGLT2. Since [18F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.

Original language	English
Pages (from-to)	16641-16649
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	64
Issue number	22
Early online date	8-Nov-2021
DOIs	https://doi.org/10.1021/acs.jmedchem.1c01269
Publication status	Published - 25-Nov-2021

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GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET TracerFinal publisher's version, 4.06 MBLicence: CC BY-NC-ND

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van der Hoek, S., Antunes, I. F., Attia, K. A., Jacquet, O., Heeres, A., Bulthuis, M., Zijlma, R., Boersma, H. H., van Goor, H., Visser, T. J., Heerspink, H. J. L., Elsinga, P. H., & Stevens, J. (2021). GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2. Journal of Medicinal Chemistry, 64(22), 16641-16649. https://doi.org/10.1021/acs.jmedchem.1c01269

van der Hoek, Sjoukje ; Antunes, Inês F ; Attia, Khaled A ; Jacquet, Olivier ; Heeres, Andre ; Bulthuis, Marian ; Zijlma, Rolf ; Boersma, Hendrikus H ; van Goor, Harry ; Visser, Ton J ; Heerspink, Hiddo J L ; Elsinga, Philip H ; Stevens, Jasper. / GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2. In: Journal of Medicinal Chemistry. 2021 ; Vol. 64, No. 22. pp. 16641-16649.

@article{ac16ee37b2494ecb88541bab6994a07c,

title = "GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2",

abstract = "Inhibition of the sodium-glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [18F]canagliflozin was developed via a Cu-mediated 18F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [18F]canagliflozin with a yield of 0.5-3% (n = 4) and a purity of >95%. Autoradiography showed [18F]canagliflozin binding in human kidney sections containing SGLT2. Since [18F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.",

author = "{van der Hoek}, Sjoukje and Antunes, {In{\^e}s F} and Attia, {Khaled A} and Olivier Jacquet and Andre Heeres and Marian Bulthuis and Rolf Zijlma and Boersma, {Hendrikus H} and {van Goor}, Harry and Visser, {Ton J} and Heerspink, {Hiddo J L} and Elsinga, {Philip H} and Jasper Stevens",

year = "2021",

month = nov,

day = "25",

doi = "10.1021/acs.jmedchem.1c01269",

language = "English",

volume = "64",

pages = "16641--16649",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "AMER CHEMICAL SOC",

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van der Hoek, S , Antunes, IF, Attia, KA, Jacquet, O, Heeres, A, Bulthuis, M, Zijlma, R, Boersma, HH , van Goor, H, Visser, TJ, Heerspink, HJL , Elsinga, PH & Stevens, J 2021, 'GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2', Journal of Medicinal Chemistry, vol. 64, no. 22, pp. 16641-16649. https://doi.org/10.1021/acs.jmedchem.1c01269

GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2. / van der Hoek, Sjoukje ; Antunes, Inês F; Attia, Khaled A; Jacquet, Olivier; Heeres, Andre; Bulthuis, Marian; Zijlma, Rolf; Boersma, Hendrikus H ; van Goor, Harry; Visser, Ton J; Heerspink, Hiddo J L ; Elsinga, Philip H ; Stevens, Jasper.

In: Journal of Medicinal Chemistry, Vol. 64, No. 22, 25.11.2021, p. 16641-16649.

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

TY - JOUR

T1 - GMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium-Glucose Cotransporter 2

AU - van der Hoek, Sjoukje

AU - Antunes, Inês F

AU - Attia, Khaled A

AU - Jacquet, Olivier

AU - Heeres, Andre

AU - Bulthuis, Marian

AU - Zijlma, Rolf

AU - Boersma, Hendrikus H

AU - van Goor, Harry

AU - Visser, Ton J

AU - Heerspink, Hiddo J L

AU - Elsinga, Philip H

AU - Stevens, Jasper

PY - 2021/11/25

Y1 - 2021/11/25

N2 - Inhibition of the sodium-glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [18F]canagliflozin was developed via a Cu-mediated 18F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [18F]canagliflozin with a yield of 0.5-3% (n = 4) and a purity of >95%. Autoradiography showed [18F]canagliflozin binding in human kidney sections containing SGLT2. Since [18F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.

AB - Inhibition of the sodium-glucose cotransporter 2 (SGLT2) by canagliflozin in type 2 diabetes mellitus results in large between-patient variability in clinical response. To better understand this variability, the positron emission tomography (PET) tracer [18F]canagliflozin was developed via a Cu-mediated 18F-fluorination of its boronic ester precursor with a radiochemical yield of 2.0 ± 1.9% and a purity of >95%. The GMP automated synthesis originated [18F]canagliflozin with a yield of 0.5-3% (n = 4) and a purity of >95%. Autoradiography showed [18F]canagliflozin binding in human kidney sections containing SGLT2. Since [18F]canagliflozin is the isotopologue of the extensively characterized drug canagliflozin and thus shares its toxicological and pharmacological characteristics, it enables its immediate use in patients.

U2 - 10.1021/acs.jmedchem.1c01269

DO - 10.1021/acs.jmedchem.1c01269

M3 - Article

C2 - 34748702

VL - 64

SP - 16641

EP - 16649

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 22

ER -