Systemic sclerosis–associated interstitial lung disease (SSc-ILD) is a life-threatening complication of systemic sclerosis, characterised by variable progression and challenging prognosis. While pulmonary function tests (PFTs) and high-resolution CT (HRCT) are the standard tools for monitoring disease, they often fall short in predicting outcomes, especially at early stages. Conventional assessments are frequently hindered by the multisystem nature of systemic sclerosis, which can impact patient performance and skew functional results.
Against this backdrop, the use of metabolic imaging with [18F]FDG PET/CT offers a novel approach to evaluate disease activity at a cellular level. A recent prospective study has explored how PET/CT-derived markers, particularly the standardised uptake values SUVmax and SUVmin, can predict survival in patients with SSc-ILD. The results suggest that combining these imaging biomarkers with established physiological indices such as ILD-GAP could enhance risk stratification and support more timely treatment decisions.
PET/CT Metrics Offer Insight into Disease Activity
[18F]FDG PET/CT enables non-invasive imaging of metabolic processes in vivo, offering a window into inflammatory and fibrotic activity within the lungs. In this study, a cohort of 45 patients with confirmed SSc-ILD underwent PET/CT imaging as part of a comprehensive assessment that also included HRCT and PFTs. The analysis focused on SUVmax, the highest level of FDG uptake in affected lung areas, and SUVmin, the lowest uptake measured in normal-appearing lung tissue. The ratio of these two values, termed the target-to-background ratio (TBR), was also considered.
Findings showed that increased SUVmax and SUVmin were both associated with poorer overall survival, although SUVmin stood out as an independent predictor when considered alongside the ILD-GAP index. SUVmin may reflect subtle, widespread metabolic changes within lung tissue that has not yet undergone visible structural damage, capturing early inflammatory or fibrotic processes missed by HRCT.
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This capability is particularly important in SSc-ILD, where disease progression is often diffuse rather than focal. While SUVmax highlights localised regions of intense activity, SUVmin may serve as a surrogate for global low-grade inflammation. Such insights offer a more nuanced understanding of disease biology and may assist in identifying patients who appear clinically stable yet harbour early signs of progression.
Combining Clinical Scores and Imaging for Improved Prognosis
The ILD-GAP index is widely used to estimate mortality risk in interstitial lung diseases. It incorporates sex, age, forced vital capacity and diffusing capacity for carbon monoxide to produce a score correlated with patient outcomes. However, its reliability depends on patients being able to perform PFTs adequately, which is not always feasible in systemic sclerosis due to joint stiffness, muscle weakness or pulmonary hypertension. In this context, PET/CT biomarkers provide complementary information that does not rely on patient effort. In this study, SUVmin remained prognostically significant even after adjusting for ILD-GAP scores. A modified scoring system (mGAP) was constructed by integrating SUVmin into the ILD-GAP framework, improving its ability to stratify patients according to survival risk.
Patients with SUVmin above the identified threshold had substantially lower two- and five-year survival rates, despite no significant abnormalities on HRCT. This highlights the potential of metabolic imaging to detect clinically important changes earlier than structural imaging or functional testing. Furthermore, TBR also demonstrated prognostic relevance, although it did not retain independence in multivariate analyses. Nonetheless, TBR may prove useful in situations where PFT data are unavailable or unreliable, offering a normalised metric of FDG uptake that adjusts for baseline metabolic activity.
Clinical Relevance and Future Applications
The identification of SUVmin as an independent prognostic marker carries significant clinical implications. It opens the possibility of earlier intervention in patients who might otherwise not qualify for treatment escalation based on traditional assessments. Present guidelines often delay changes in therapy until clear evidence of progression is established through PFTs or HRCT, which can take many months to emerge. Incorporating PET/CT findings could support a more proactive approach, selecting patients for closer monitoring, enrolment in clinical trials or initiation of second-line therapies. This approach could be particularly beneficial for individuals who are not responsive to initial immunosuppressive treatment or those who may benefit from antifibrotic therapies currently reserved for more advanced disease stages.
Although the study cohort was relatively small, it is the largest prospective PET/CT investigation in SSc-ILD to date. The findings contribute to a growing body of evidence that supports the use of functional imaging in interstitial lung disease. In future, combining PET/CT data with serum biomarkers and advanced imaging techniques could enhance diagnostic precision and therapeutic targeting. Functional imaging may also serve as a valuable tool in assessing treatment response, especially in trials evaluating novel anti-inflammatory or antifibrotic agents.
The study reinforced the prognostic value of [18F]FDG PET/CT in systemic sclerosis–associated interstitial lung disease. Among the various PET-derived markers, SUVmin—reflecting uptake in normal-appearing lung—was shown to be an independent predictor of mortality, adding significant value to established clinical scoring systems. When incorporated into a modified ILD-GAP index, PET/CT data improved risk stratification and offered a more refined approach to guiding clinical decisions. These findings highlight the potential role of metabolic imaging in bridging the gap between structural assessments and functional tests, supporting earlier intervention and more tailored treatment in patients with SSc-ILD.
Source: The Journal of Nuclear Medicine
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