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

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 [F]canagliflozin was developed via a Cu-mediated 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 [F]canagliflozin with a yield of 0.5-3% ( = 4) and a purity of >95%. Autoradiography showed [F]canagliflozin binding in human kidney sections containing SGLT2. Since [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.