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

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.

SUBMITTER: van der Hoek S 

PROVIDER: S-EPMC8631709 | biostudies-literature |

REPOSITORIES: biostudies-literature