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

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

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

André Heeres, Sjoukje van der Hoek, Inês F. Antunes, Khaled A. Attia, Olivier Jacquet, 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

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

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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	Dutch
Journal	Journal of Medicinal Chemistry
Publication status	Published - 8 Nov 2021

Keywords

sodium–glucose cotransporter
sodium
glucose
diabetes

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acs.jmedchem.1c01269Final published version, 4.06 MBLicence: CC BY-NC-ND

Cite this

@article{ac3a9150ca874674add4fdf20ac170a3,

title = "GMP Compliant Synthesis of 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 = "natrium-glucose-cotransporter, natrium, glucose, diabetes, sodium–glucose cotransporter, sodium, glucose, diabetes",

author = "Andr{\'e} Heeres and {van der Hoek}, Sjoukje and Antunes, {In{\^e}s F.} and Attia, {Khaled A.} and Olivier Jacquet 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 = "8",

language = "Dutch",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

}

TY - JOUR

T1 - GMP Compliant Synthesis of Canagliflozin, a Novel PET Tracer for the Sodium−Glucose Cotransporter 2

AU - Heeres, André

AU - van der Hoek, Sjoukje

AU - Antunes, Inês F.

AU - Attia, Khaled A.

AU - Jacquet, Olivier

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 - natrium-glucose-cotransporter

KW - natrium

KW - glucose

KW - diabetes

KW - sodium–glucose cotransporter

KW - sodium

KW - glucose

KW - diabetes

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

M3 - Article

SN - 0022-2623

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

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

Abstract

Keywords

Access to Document

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Cite this

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

Abstract

Keywords

Access to Document

Other files and links

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

Sustainable building blocks at the Hanze

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

Biobased/circular chemistry at the Hanze.

Cite this