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; André Heeres; Marian  Bulthuis; Rolf Zijlma; Hendrikus H.  Boersma; Harry van Goor; Ton J. Visser; Hiddo J. L.  Heerspink; Philip H.  Elsinga; Jasper  Stevens

doi:https://doi.org/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, André Heeres, Marian Bulthuis, Rolf Zijlma, Hendrikus H. Boersma, Harry van Goor, Ton J. Visser, Hiddo J. L. Heerspink, Philip H. Elsinga, Jasper Stevens

Biobased Chemistry & Refinery

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

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
Journal	Journal of Medicinal Chemistry
Volume	64
Issue number	22
DOIs	https://doi.org/10.1021/acs.jmedchem.1c01269
Publication status	Published - 8 Nov 2021

Keywords

PET tracer
glucose
canagliflozin

Access to Document

https://doi.org/10.1021/acs.jmedchem.1c01269Licence: CC BY-NC-ND

11 Article
1 Report
1 Poster
1 Patent

Substituted anilides from chitin-based 3-acetamido-furfural
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Research output: Contribution to journal › Article › Academic › peer-review

Open Access
Advantages of Producing Aromatics from Propene over Ethene Using Zeolite-Based Catalysts
Butolia, P. S., Xi, X., Winkelman, J. G. M., Stuart, M. C. A., van Akker, M., Heeres, A., Heeres, H. J. & Xie, J., 11 Oct 2022, In: Chemie Ingenieur Technik - CIT. 94, 11, p. 1845-1852
Research output: Contribution to journal › Article › Academic › peer-review

Open Access
A time- and space-resolved catalyst deactivation study on the conversion of glycerol to aromatics using H-ZSM-5
He, S., Goldhoorn, H. R., Tegudeer, Z., Chandel, A., Heeres, A., Stuart, M. C. A. & Heeres, H. J., 15 Apr 2022, In: Chemical Engineering Journal. 434, 134620.
Research output: Contribution to journal › Article › Academic › peer-review

Open Access

6 Invited talk
1 Oral presentation

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Activity: Talk or presentation › Invited talk
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16 Jan 2023
Activity: Talk or presentation › Invited talk
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Activity: Talk or presentation › Oral presentation

Cite this

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

@article{e8f3cd38c4d749efadb9b247fe2349d4,

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.",

keywords = "canagliflozine, PET tracer, glucose, canagliflozin",

author = "{van der Hoek}, Sjoukje and Antunes, {In{\^e}s F.} and Attia, {Khaled A.} and Olivier Jacquet and Andr{\'e} 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",

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month = nov,

day = "8",

doi = "https://doi.org/10.1021/acs.jmedchem.1c01269",

language = "English",

volume = "64",

pages = "16641–16649",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "22",

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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

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, André

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 - 2021/11/8

Y1 - 2021/11/8

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.

KW - canagliflozine

KW - PET tracer

KW - glucose

KW - canagliflozin

U2 - https://doi.org/10.1021/acs.jmedchem.1c01269

DO - https://doi.org/10.1021/acs.jmedchem.1c01269

M3 - Article

SN - 0022-2623

VL - 64

SP - 16641

EP - 16649

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 22

ER -

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

Abstract

Keywords

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Research output

Substituted anilides from chitin-based 3-acetamido-furfural

Advantages of Producing Aromatics from Propene over Ethene Using Zeolite-Based Catalysts

A time- and space-resolved catalyst deactivation study on the conversion of glycerol to aromatics using H-ZSM-5

Activities

Barn Talk Towards Renewable Molecules: Koppeling van de energiesector aan de chemische sector (materialentransitie)

IHOG Innovatiehub Oost-Groningen

Sustainable building blocks at the Hanze

Cite this