Deuterium- and Fluorine-18-Labeled Glutaminea PET Imaging Agent with Enhanced In Vivo Stability

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Molecular Imaging

Background:

• Glutamine metabolism is crucial in various physiological and pathological processes, including cancer.
• Current imaging agents for glutamine metabolism may have limitations in in vivo stability.
• Development of novel radiotracers with enhanced stability is needed for accurate in vivo assessment.

Purpose of the Study:

• To design, synthesize, and evaluate a novel deuterium and fluorine-18 dual-isotope labeled fluoroglutamine, (2S,4R)-[4-18F-3,3,4-d3]-fluoroglutamine (4-[18F]-FGln-d3).
• To assess the potential of 4-[18F]-FGln-d3 as a glutamine metabolic imaging agent with improved in vivo stability.
• To compare the performance of 4-[18F]-FGln-d3 with its parent compound, 4-[18F]-FGln.

Main Methods:

• Synthesis of a tetradeuterated homoserine intermediate via a six-step pathway including chiral HPLC.
• Preparation of a (2S,4S)-tosylate precursor.
• Semiautomated production of 4-[18F]-FGln-d3 and subsequent in vitro cell uptake and in vivo murine imaging studies.

Main Results:

• Successful synthesis and preparation of 4-[18F]-FGln-d3.
• 4-[18F]-FGln-d3 demonstrated similar cell uptake and comparable tumor uptake and tumor-to-muscle ratios as 4-[18F]-FGln.
• A notable finding was the moderately decreased radioactivity bone uptake for 4-[18F]-FGln-d3 at 120 min postinjection.

Conclusions:

• Preliminary data suggest enhanced in vivo stability for 4-[18F]-FGln-d3 compared to 4-[18F]-FGln.
• The improved stability warrants further investigation of 4-[18F]-FGln-d3 as a PET imaging agent.
• This novel radiotracer holds promise for probing glutamine metabolism in vivo with greater stability.