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

[Image: see text] 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 [(18)F]canagliflozin was dev...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631709/
https://www.ncbi.nlm.nih.gov/pubmed/34748702
http://dx.doi.org/10.1021/acs.jmedchem.1c01269
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author 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
author_facet 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
author_sort van der Hoek, Sjoukje
collection PubMed
description [Image: see text] 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 [(18)F]canagliflozin was developed via a Cu-mediated (18)F-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 [(18)F]canagliflozin with a yield of 0.5–3% (n = 4) and a purity of >95%. Autoradiography showed [(18)F]canagliflozin binding in human kidney sections containing SGLT2. Since [(18)F]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.
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spelling pubmed-86317092021-12-01 GMP Compliant Synthesis of [(18)F]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 J Med Chem [Image: see text] 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 [(18)F]canagliflozin was developed via a Cu-mediated (18)F-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 [(18)F]canagliflozin with a yield of 0.5–3% (n = 4) and a purity of >95%. Autoradiography showed [(18)F]canagliflozin binding in human kidney sections containing SGLT2. Since [(18)F]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. American Chemical Society 2021-11-08 2021-11-25 /pmc/articles/PMC8631709/ /pubmed/34748702 http://dx.doi.org/10.1021/acs.jmedchem.1c01269 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle 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 [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title GMP Compliant Synthesis of [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title_full GMP Compliant Synthesis of [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title_fullStr GMP Compliant Synthesis of [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title_full_unstemmed GMP Compliant Synthesis of [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title_short GMP Compliant Synthesis of [(18)F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
title_sort gmp compliant synthesis of [(18)f]canagliflozin, a novel pet tracer for the sodium–glucose cotransporter 2
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631709/
https://www.ncbi.nlm.nih.gov/pubmed/34748702
http://dx.doi.org/10.1021/acs.jmedchem.1c01269
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