Molecular imaging of fibroblast activation in systemic sclerosis using [¹⁸F]AlF-NOTA-FAPI-04 PET/CT: a prospective...

Area of Science:

• Radiology and Nuclear Medicine
• Immunology and Rheumatology
• Medical Imaging

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease characterized by widespread fibroblast activation and fibrosis.
• Accurate assessment of multi-organ involvement and disease severity in SSc is crucial for effective management.
• Current imaging modalities may not fully capture the extent of fibroblast activation across all affected organs.

Purpose of the Study:

• To evaluate the utility of [¹⁸F]AlF-NOTA-FAPI-04 Positron Emission Tomography/Computed Tomography (PET/CT) for whole-body assessment of fibroblast activation in SSc.
• To correlate organ-specific tracer uptake with clinical indicators of SSc severity and multi-organ dysfunction.
• To explore inter-organ metabolic correlations in SSc using this novel imaging tracer.

Main Methods:

• A prospective cohort study involving 31 SSc patients and 21 non-SSc controls.
• Total-body [¹⁸F]AlF-NOTA-FAPI-04 PET/CT imaging was performed on all participants.
• Quantitative uptake parameters (SUVmean, SUVmax) were measured in key organs (lungs, heart, kidneys, muscles, esophagus, skin), with clinical assessments performed concurrently.

Main Results:

• Elevated [¹⁸F]AlF-NOTA-FAPI-04 uptake was prevalent in SSc lungs (96.8%), heart (35.5%), kidneys, and skeletal muscles.
• SSc patients showed significantly higher lung and cardiac uptake compared to controls.
• Increased renal uptake correlated with renal impairment, and muscular uptake aligned with myopathy; esophageal and skin uptake were not significant.
• Significant metabolic coupling was observed between pulmonary, cardiac, and renal systems.

Conclusions:

• [¹⁸F]AlF-NOTA-FAPI-04 PET/CT serves as a noninvasive platform for mapping systemic fibroblast activation in SSc.
• The imaging demonstrates potential for detecting fibrotic burden and characterizing inter-organ metabolic profiles in SSc.
• Sensitivity for gastrointestinal and cutaneous involvement requires further optimization.