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: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

University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology
University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular imaging
Symeres BV
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology

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
Number of pages	9
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

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
van der Loo, C., Kaniraj, J. P., Wang, T., Pouwer, K., Broekman, O., Borst, M., Heeres, A., Deuss, P. & Minnaard, A., 5 Oct 2023, In: Organic and Biomolecular Chemistry. 21, 41, p. 8372-8378 7 p.
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 8 p.
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

De biobased/circulaire transitie (Hanze) - Konnect-lezing Eemshaven
Heeres, A. (Speaker)
8 Feb 2023
Activity: Talk or presentation › Invited talk
Kick-off Interreg EMPATHI: End-of-life options for PHA‘s
Heeres, A. (Speaker)
19 Apr 2023
Activity: Talk or presentation › Invited talk
Biobased/circular chemistry at the Hanze.
Heeres, A. (Speaker) & Keller, E. (Speaker)
2 Jun 2023
Activity: Talk or presentation › Invited talk

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

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

language = "English",

volume = "64",

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publisher = "American Chemical Society",

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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 - 10.1021/acs.jmedchem.1c01269

DO - 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

Access to Document

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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

De biobased/circulaire transitie (Hanze) - Konnect-lezing Eemshaven

Kick-off Interreg EMPATHI: End-of-life options for PHA‘s

Biobased/circular chemistry at the Hanze.

Cite this