Open AccessGMP Compliant Synthesis of [18F]Canagliflozin, a Novel PET Tracer for the Sodium–Glucose Cotransporter 2
Author(s) -
Sjoukje van der Hoek,
Inês Farinha Antunes,
Khaled Attia,
Olivier Jacquet,
André Heeres,
Marian Bulthuis,
Rolf Zijlma,
Hendrikus H. Boersma,
Harry van Goor,
T. Visser,
Hiddo J.L. Heerspink,
Philip H. Elsinga,
Jasper Stevens
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c01269
Subject(s) - canagliflozin , chemistry , tracer , sodium , empagliflozin , radiochemistry , pharmacology , endocrinology , diabetes mellitus , type 2 diabetes , medicine , organic chemistry , physics , nuclear physics
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 [ 18 F]canagliflozin was developed via a Cu-mediated 18 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 [ 18 F]canagliflozin with a yield of 0.5-3% ( n = 4) and a purity of >95%. Autoradiography showed [ 18 F]canagliflozin binding in human kidney sections containing SGLT2. Since [ 18 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.