A Macrophage-Specific PET Tracer for Grading Acute Liver Injury

Area of Science:

• Medical Imaging
• Biomarker Development
• Hepatology

Background:

• Accurate assessment of acute liver injury (ALI) is challenging due to a lack of reliable biomarkers.
• Activated macrophages are key players in ALI progression, but their quantification is difficult.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) tracer, [68Ga]Ga-VUIIS1008, for noninvasive imaging of hepatic macrophages in ALI.
• To assess the tracer's ability to correlate with disease severity and progression.

Main Methods:

• Synthesis and preclinical evaluation of the TSPO-targeting PET tracer [68Ga]Ga-VUIIS1008.
• In vivo PET imaging in healthy and ALI mouse models.
• Correlation analysis between tracer uptake and histopathological scores.

Main Results:

• [68Ga]Ga-VUIIS1008 demonstrated specific targeting of activated macrophages in ALI models.
• The tracer exhibited rapid hepatobiliary clearance in healthy mice, minimizing background.
• Significant correlation was observed between hepatic tracer retention and ALI severity (R² = 0.8155, p < 0.0001).

Conclusions:

• [68Ga]Ga-VUIIS1008 is a promising PET tracer for noninvasive, quantitative assessment of hepatic inflammation in ALI.
• The tracer's ability to reflect disease severity suggests its potential for clinical translation in ALI diagnosis and grading.