A PROOF-OF-CONCEPT study suggests that a VAP-1–targeted sarcoidosis PET/CT tracer can detect pulmonary and systemic inflammatory activity more clearly than background uptake in healthy controls.
Sarcoidosis PET/CT Targets Inflammatory Pathways
Pulmonary sarcoidosis is the most common and clinically relevant manifestation of this multisystem granulomatous disease, yet imaging tools that accurately reflect inflammatory activity remain limited. Vascular adhesion protein-1 (VAP-1) is known to mediate leukocyte trafficking into inflamed tissue, making it an attractive molecular target. The novel radiotracer [⁶⁸Ga]Ga-DOTA-Siglec-9 binds specifically to VAP-1, enabling visualisation of inflammatory processes using PET/CT. In this study, investigators explored whether sarcoidosis PET/CT using this tracer could feasibly identify disease activity in the lungs and beyond, addressing a key unmet need in disease assessment and monitoring.
Sarcoidosis PET/CT Assessed in Small Clinical Trial
The study enrolled six patients with stage 2 pulmonary sarcoidosis, diagnosed using standard clinical, radiological, and histological criteria. Participants underwent [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT scanning, with tracer uptake quantified in lung tissue, mediastinal lymph nodes, and other organs associated with systemic inflammation. Control groups included six healthy volunteers and a patient with lung cancer, allowing comparison across inflammatory and non-inflammatory states. Although modest in size, the trial was designed to establish feasibility and generate early efficacy signals rather than to assess clinical outcomes.
Sarcoidosis PET/CT Shows Higher Uptake in Disease
Patients with sarcoidosis demonstrated significantly higher tracer uptake than healthy controls in both lungs and mediastinal lymph nodes, indicating active pulmonary inflammation. Importantly, increased uptake was also observed in the liver, spleen, bone marrow, and bone, supporting the ability of sarcoidosis PET/CT to detect systemic inflammatory involvement. The magnitude and consistency of these differences suggest that VAP-1–targeted imaging may provide a sensitive marker of inflammatory burden, with potential applications in disease phenotyping and treatment monitoring.
While limited by its small sample size, this study supports further investigation of [⁶⁸Ga]Ga-DOTA-Siglec-9 sarcoidosis PET/CT in larger cohorts. Future research will need to clarify its role in guiding clinical decision-making and assessing therapeutic response.
Reference
Dadson P et al. Proof-of-concept PET imaging of pulmonary sarcoidosis using VAP-1-targeted radiotracer [68Ga]Ga-DOTA-Siglec-9. Respir Res. 2025;DOI: 10.1186/s12931-025-03455-8.
