A Clinical PET Imaging Tracer ([¹⁸F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in...

Area of Science:

• Biochemistry
• Oncology
• Radiochemistry

Background:

• Pyruvate kinase M2 (PKM2) is crucial for cancer metabolism and overexpressed in glioblastoma (GBM).
• Targeting PKM2 offers a potential strategy for GBM treatment and monitoring.
• A specific PET tracer is needed to visualize PKM2 activity in vivo.

Purpose of the Study:

• To develop and validate a novel PET tracer, [18F]DASA-23, for imaging PKM2 in GBM.
• To assess the tracer's ability to detect GBM and differentiate it from healthy brain tissue.
• To evaluate the tracer's translation to human studies for clinical application.

Main Methods:

• Synthesis and radiochemical characterization of [18F]DASA-23.
• In vitro testing in GBM cell cultures and in vivo testing in mouse GBM xenograft models.
• Clinical evaluation in healthy human volunteers and a pilot cohort of GBM patients under FDA oversight.

Main Results:

• [18F]DASA-23 demonstrated high tumor-to-brain ratios in mouse models (3.6 ± 0.5).
• The tracer successfully crossed the blood-brain barrier in humans and was rapidly cleared.
• In GBM patients, [18F]DASA-23 outlined tumors, showed elevated uptake in GBMs versus normal brain, and identified metabolic nonresponders early.

Conclusions:

• [18F]DASA-23 is a novel PET tracer capable of visualizing aberrantly expressed PKM2 in human subjects for the first time.
• The tracer's ability to delineate GBM and assess metabolic response supports its clinical utility.
• Further clinical evaluation is warranted to confirm [18F]DASA-23's role in monitoring GBM therapy.