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

    Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
    Pages (from-to)16641–16649
    Number of pages9
    JournalJournal of Medicinal Chemistry
    Volume64
    Issue number22
    DOIs
    Publication statusPublished - 8 Nov 2021

    Keywords

    • PET tracer
    • glucose
    • canagliflozin

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