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

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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 languageDutch
JournalJournal of Medicinal Chemistry
Publication statusPublished - 8 Nov 2021

Keywords

  • sodium–glucose cotransporter
  • sodium
  • glucose
  • diabetes

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