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

• Published in: Journal of medicinal chemistry Vol. 64; no. 22; pp. 16641 - 16649
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.11.2021; Amer Chemical Soc
• Subjects: Canagliflozin - chemical synthesis; Chemistry, Medicinal; Fluorine Radioisotopes; Humans; Life Sciences & Biomedicine; Molecular Imaging - methods; Pharmacology & Pharmacy; Positron-Emission Tomography - methods; Radioactive Tracers; Science & Technology; Sodium-Glucose Transporter 2 - analysis; Sodium-Glucose Transporter 2 Inhibitors - chemical synthesis; POSITRON-EMISSION-TOMOGRAPHY; DAPAGLIFLOZIN; INHIBITOR; THIOPHENE; DISCOVERY; MEDIATED F-18-FLUORINATION
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.1c01269

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.