Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
J Med Chem. 2021 Nov 25;64(22):16641-16649. doi: 10.1021/acs.jmedchem.1c01269. Epub 2021 Nov 8.
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.
在 2 型糖尿病中，通过钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂卡格列净治疗会导致临床反应的患者间个体差异较大。为了更好地理解这种变异性，通过其硼酸酯前体的 Cu 介导的 F-氟化作用，开发了正电子发射断层扫描（PET）示踪剂 [F]卡格列净，放射化学产率为 2.0 ± 1.9%，纯度 >95%。符合 GMP 标准的自动化合成方法使 [F]卡格列净的产率达到 0.5-3%（ = 4），纯度 >95%。放射自显影显示，在含有 SGLT2 的人肾切片中存在 [F]卡格列净结合。由于 [F]卡格列净是经过广泛特征描述的药物卡格列净的同位素类似物，因此具有相同的毒理学和药理学特征，可立即在患者中使用。
