Novel tracer can identify lung lesions in those with connective tissue diseases

A positron emission tomography (PET) or computed tomography (CT) scan with a novel radiotracer may offer a sensitive, noninvasive tool for diagnosing interstitial lung disease (ILD) in patients with connective tissue disease, according to researchers at Sichuan Provincial People’s Hospital in Sichuan, China. The study, published in the journal Respiratory Research in November 2025, revealed that patients with connective tissue disease–associated ILD had significantly higher uptake of the ¹⁸F-FAPI-RGD tracer on PET/CT scans compared with those without lung involvement.

Connective tissue diseases impact connective tissues, such as cartilage and fat. More than 200 disorders impact connective tissues, including autoimmune diseases, genetic disorders, and even cancer.

Interstitial lung disease is a group of disorders where lung tissues are inflamed and damaged. This is most commonly seen in patients with the tissue disorders such as rheumatoid arthritis, systemic sclerosis, and idiopathic inflammatory myopathy, which impacts the muscles.

In the Respiratory Research paper, researchers, led by corresponding author Wubin Long from the hospital’s department of rheumatology and immunology, studied a cohort of 52 patients, including 35 with connective tissue disease-associated ILD and 17 with connective tissue disease but no evidence of ILD.

The entire cohort underwent standard clinical assessment, including lung function tests and high-resolution CT, as well as receiving ¹⁸F-FAPI-RGD PET/CT imaging.

“The goal was to assess whether uptake of the new tracer in the lungs correlates with ILD diagnosis,” Long told Managed Healthcare Executive.

Long explained that the imaging probe, ¹⁸F-FAPI-RGD, takes advantage of two biological targets linked to fibrotic and inflammatory processes in the lung: fibroblast activation protein and integrin receptors. Its dual-target design allows it to highlight areas of fibroblast activation and tissue remodeling, processes that precede overt fibrosis.

The results showed that patients with CTD-ILD displayed significantly higher uptake measured as maximum standardized uptake value (SUVmax) in both lungs compared with CTD patients without ILD. They also showed that the uptake in the spleen was lower among CTD-ILD patients, which caused the researchers to note it would need further investigation because it may reflect redistribution of inflammatory cells.

Additionally, bilateral lung SUVmax emerged as an independent predictor of CTD-ILD even after adjusting for age, lung function, and known biomarkers.

The results proved the tracer’s performance was strong, as the data reported an area under the receiver-operating-characteristic curve of 0.94 for distinguishing ILD from non-ILD, suggesting high diagnostic accuracy.

The authors believe the findings support ¹⁸F-FAPI-RGD PET/CT as a promising diagnostic tool in CTD-ILD, highlighting that current standard tools, especially high-resolution CT, often miss early or subtle lung involvement, while the PET/CT imaging with this new tracer could detect disease activity earlier by targeting cellular processes underlying fibrosis rather than relying solely on structural changes visible on conventional imaging.

“This may allow clinicians to detect ILD at a stage when intervention could be more effective or even prevent progression,” Long said.

Still, the research team noted that the study is small and preliminary, and the pilot nature of the study means that larger studies are required to validate the findings, assess how tracer uptake correlates with long-term disease progression or response to therapy, and truly determine whether the approach can reliably distinguish ILD from other lung conditions such as infection or pulmonary hypertension.

Nevertheless, the authors concluded that ¹⁸F-FAPI-RGD PET/CT has the potential to transform the approach to diagnosing CTD-associated ILD, offering a noninvasive and biologically grounded method that could improve early detection, guide treatment decisions, and monitor disease activity over time. If future work confirms these results, the imaging method could become an important addition to standard diagnostic tools for patients with connective tissue diseases at risk of ILD.