A ¹⁸F-labeled glucose analog: Synthesis using a click labeling method and in vitro evaluation

A ¹⁸F-labeled glucose analog, 4-[(2-[¹⁸F]fluoroethyl) -1-(β-d-glucopyranosyl)]-1H-1,2,3-triazole ([¹⁸F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/μmol vs. 23.5 GBq/μmol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [¹⁸F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [¹⁸F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1.