New PET Tracer Targets Inflammation in Pulmonary Sarcoidosis, Proof-of-Concept Study Shows
Finland: Researchers have demonstrated the potential of a novel positron emission tomography (PET) imaging approach that targets vascular adhesion protein-1 (VAP-1) to visualize pulmonary sarcoidosis more specifically than currently available techniques.
The proof-of-concept study, published in Respiratory Research, was led by Prince Dadson, MD, PhD, from the Turku PET Centre at the University of Turku, Finland, and colleagues.
Sarcoidosis is a chronic multisystem inflammatory disorder characterized by granuloma formation, with lung involvement being the most frequent and clinically significant manifestation. Molecular imaging, particularly F-18 fluorodeoxyglucose (FDG) PET/CT, is commonly used to assess disease activity. However, FDG uptake reflects general metabolic activity and is therefore nonspecific, making it difficult to distinguish inflammatory lesions from malignancy or other metabolically active tissues.
To address this limitation, the investigators explored the feasibility of a new PET radiotracer, [⁶⁸Ga]Ga-DOTA-Siglec-9, which selectively binds to VAP-1. VAP-1 is expressed on vascular endothelial cells during inflammation and plays a key role in leukocyte recruitment to inflamed tissues. By targeting this pathway, the researchers aimed to achieve more disease-specific imaging of sarcoidosis-related inflammation.
In this first-in-human evaluation, six patients with stage II pulmonary sarcoidosis (mean age 50.5 years) underwent [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT imaging. Their findings were compared with scans from six healthy male volunteers. Tracer uptake was quantified using standardized uptake values (SUVs) in the lungs, mediastinal lymph nodes, and other organs associated with systemic inflammation.
The study led to the following notable findings:
- Patients with pulmonary sarcoidosis showed significantly higher uptake of the VAP-1–targeted PET tracer in the lungs and mediastinal lymph nodes compared with healthy controls, indicating active pulmonary inflammation.
- Increased tracer uptake was also detected in the liver, spleen, bone marrow, and bone, pointing to systemic inflammatory involvement beyond the lungs.
- The observed uptake pattern reflected the multisystem nature of sarcoidosis and demonstrated the potential of VAP-1–targeted imaging to more accurately capture overall inflammatory burden.
The researchers noted that this targeted approach could potentially overcome key shortcomings of FDG-PET/CT. By focusing on endothelial inflammation rather than general glucose metabolism, VAP-1–based imaging may improve differentiation between inflammatory and malignant lesions and offer a more specific tool for assessing disease activity and monitoring treatment response.
However, the authors emphasized that the findings are preliminary. The study involved a small number of participants and lacked ethnic diversity, an important consideration given that sarcoidosis severity and pulmonary involvement are known to vary across populations. They stressed the need for larger, more diverse cohorts to validate the diagnostic performance and clinical utility of this imaging technique.
Despite these limitations, the study adds to the growing body of evidence supporting VAP-1 as a relevant molecular target in inflammatory diseases.
The authors concluded that [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT shows promise as a novel imaging modality for pulmonary sarcoidosis and warrants further investigation in larger clinical studies to better define its role in routine practice.
Reference:
Dadson, P., Ylä-Outinen, H., Kalliokoski, K. et al. Proof-of-concept PET imaging of pulmonary sarcoidosis using VAP-1-targeted radiotracer [68Ga]Ga-DOTA-Siglec-9. Respir Res (2025). https://doi.org/10.1186/s12931-025-03455-8
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