A Macrophage-Specific PET Tracer for Grading Acute Liver Injury

Accurate assessment of acute liver injury (ALI) is hindered by a lack of reliable biomarkers. Addressing this, we developed a PET tracer, [⁶⁸Ga]Ga-VUIIS1008, designed to specifically target the translocator protein (TSPO) on activated macrophages during ALI progression. The probe enabled noninvasive visualization and quantification of hepatic macrophages in preclinical models. In healthy mice, its low molecular weight facilitated rapid hepatobiliary clearance, yielding a minimal liver background (%ID/g _liver = 4.95 ± 0.49 at 0.5 h). Conversely, injured livers exhibited a pathology-driven shift to TSPO-mediated retention that correlated strongly with histopathological severity (R² = 0.8155, p <0.0001). This dynamic transition allowed sensitive discrimination of disease progression across two distinct ALI models. By providing an early, quantitative, and whole-organ measure of inflammatory burden, [⁶⁸Ga]Ga-VUIIS1008 demonstrates a strong translational potential to bridge the gap between preclinical liver injury assessment and clinical diagnosis, offering a promising tool for ALI grading.