Advancing diagnostics in sarcoidosis and ILD: FDG-PET and immuno-PET innovations

Sarcoidosis and interstitial lung diseases (ILDs) are heterogeneous pulmonary disorders in which the interplay between inflammation and fibrosis determines both prognosis and treatment strategy. Traditional diagnostic methods such as high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) provide important structural and physiological insights but often fail to distinguish active inflammation from irreversible fibrotic changes. Molecular imaging using positron emission tomography (PET) may offer complementary information.

This thesis investigates the clinical value of two PET-based imaging modalities, FDG-PET and immuno-PET with [89Zr]Zr-rituximab, in assessing disease activity, guiding therapy, and improving phenotypic characterization in sarcoidosis and ILD.

In Part I, we explore the role of FDG-PET/CT in pulmonary sarcoidosis and fibrotic ILD. FDG uptake was found to reflect active inflammation and correlated better with clinical markers than anatomical imaging alone. A novel volumetric PET method was validated to quantify global lung inflammation and demonstrated better reproducibility and correlation with disease activity than conventional SUVmax-based metrics. Additionally, we examined the value of integrating quantitative CT histogram features with metabolic PET parameters to improve ILD subtyping. This integrated radiomics approach enhanced disease characterization and may support precision diagnostics in clinical practice.

Part II focuses on immuno-PET using [89Zr]Zr-rituximab, a radiolabeled anti-CD20 monoclonal antibody. This technique visualizes in vivo B-cell activity and was evaluated in the RITUX-IP study, a prospective, investigator-initiated trial in patients with therapy-refractory fibrotic ILD. The results showed that [89Zr]Zr-rituximab PET/CT can detect variable pulmonary and systemic CD20+ uptake, which corresponded with functional treatment response in certain patients. Interestingly, altered splenic uptake patterns were found in non-responders, suggesting a possible role of the spleen in treatment resistance via systemic immune mechanisms.

Together, the studies presented in this thesis demonstrate that PET imaging can go beyond morphology and function to reveal immunopathological activity in vivo. FDG-PET captures active inflammation, while [89Zr]Zr-rituximab immuno-PET enables visualization of disease-driving immune cell populations. These insights support a shift toward personalized imaging biomarkers in ILD, helping to select patients for anti-inflammatory or antifibrotic therapy, monitor response, and understand disease heterogeneity at a molecular level.

Future research should validate these findings in larger cohorts and focus on integrating PET data with clinical, serological, and molecular parameters. Such efforts will be crucial to developing predictive models that support individualized treatment decisions and improve outcomes in patients with complex interstitial lung diseases.