Mapping Arginase Expression with ¹⁸F-Fluorinated Late-Generation Arginase Inhibitors Derived from Quaternary α-Amino...

Area of Science:

• Biomedical imaging
• Radiochemistry
• Molecular imaging

Background:

• Arginase enzyme activity is linked to inflammation and cancer.
• Developing effective PET tracers for arginase is crucial for disease staging and treatment monitoring.

Purpose of the Study:

• To synthesize and evaluate novel ¹⁸F-labeled arginase inhibitors as PET tracers.
• To assess the in vitro and in vivo performance of these radiotracers for imaging arginase expression.

Main Methods:

• Copper-mediated fluorodeboronation was used to radiolabel arginase inhibitors.
• Binding assays, autoradiography, and small-animal PET imaging were employed for evaluation.
• PC3 and LNCaP cells, a guinea pig asthma model, and xenografted mice were utilized.

Main Results:

• Two ¹⁸F-labeled inhibitors, ¹⁸F-FMARS and ¹⁸F-FBMARS, were successfully synthesized.
• Specific binding was observed in cells and lung tissues, with up to 75% blockade by inhibitors.
• PET imaging revealed rapid clearance, arginase-mediated uptake, and selective tumor accumulation of the tracers.

Conclusions:

• ¹⁸F-FMARS and ¹⁸F-FBMARS are potential PET tracers for mapping arginase-related pathologies.
• ¹⁸F-FBMARS demonstrated superior performance in PET imaging, warranting further investigation for clinical applications.
• These tracers may help identify patients eligible for arginase inhibitor therapies.