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

Area of Science:

• Radiochemistry
• Molecular Imaging
• Biochemistry

Background:

• Development of novel radiotracers for Positron Emission Tomography (PET) imaging is crucial for disease diagnosis.
• Glucose analogs labeled with Fluorine-18 ((18)F) are widely used, but their synthesis can be time-consuming and inefficient.
• Click chemistry presents a promising alternative for rapid radiolabeling.

Purpose of the Study:

• To synthesize and evaluate a novel (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), using click chemistry.
• To assess the in vitro cellular uptake and transport of [(18)F]1 via glucose transporter 1 (Glut-1).
• To determine if [(18)F]1 serves as a substrate for hexokinase.

Main Methods:

• Synthesis of [(18)F]1 using a click labeling reaction.
• Comparison of click labeling with conventional radiolabeling methods in terms of yield, specific activity, and synthesis time.
• In vitro evaluation of cellular uptake in SNU-C5 cells.
• Assessment of hexokinase substrate potential.

Main Results:

• The click labeling method yielded a higher decay-corrected radiochemical yield (30% vs. 21%) and specific activity (59.9 GBq/μmol vs. 23.5 GBq/μmol) compared to conventional methods.
• Synthesis time was reduced using click chemistry (75–80 min vs. 95–100 min).
• In vitro studies showed that [(18)F]1 is not a hexokinase substrate and exhibits low, non-specific cellular uptake.

Conclusions:

• Click chemistry provides a rapid, efficient, and functional group-tolerant method for synthesizing (18)F-labeled compounds.
• The triazole moiety at the C1 position of [(18)F]1 hinders its utility as a substrate for hexokinase and its transport via Glut-1.
• This novel tracer is not suitable for imaging processes relying on hexokinase phosphorylation or Glut-1 facilitated diffusion.