Pulmonary [¹⁸F]FDG uptake demonstrates phenotypic PET behaviour in non-specific interstitial pneumonitis and refines risk stratification.

Abstract

Effective prognostic biomarkers in Non-specific Interstitial Pneumonitis (NSIP) are limited. To investigate the potential of [¹⁸F]FDG PET/CT to predict mortality in NSIP and to assess its relationship with physiological indices and the Interstitial Lung Disease - Gender-Age-Physiology (ILD-GAP) score. Ninety-six patients with a multidisciplinary team-confirmed diagnosis of NSIP (40 male, 56 female; mean age 59.8 ± 9.8 years) underwent baseline [¹⁸F]FDG PET/CT and 83 patients completed full pulmonary function testing. Pulmonary uptake of [¹⁸F]FDG was quantified using region-of-interest analysis as the maximum uptake in diseased lung (SUV_max) and the background uptake in visually normal lung (SUV_min). A target-to-background (TBR) ratio was calculated as SUV_max /SUV_min. Kaplan-Meier survival analysis examined associations between the [¹⁸F]FDG PET/CT metrics, the pulmonary function tests and ILD-GAP scores. Stepwise forward Wald multivariable Cox regression assessed independence of the significant [¹⁸F]FDG PET/CT parameters from the ILD-GAP index. The modified ILD-GAP (mGAP) models were generated by incorporating the [¹⁸F]FDG PET/CT data into the ILD-GAP index. 65 patients died during a mean follow up of 83.2 ± 48.2 months. Mean ± SD SUV_max, SUV_min and TBR were 3.2 ± 1.2, 0.6 ± 0.3 and 6.0 ± 2.4, respectively. Mortality was associated with higher SUV_max (median cutoff ≥ 2.9, p = 0.038) and higher SUV_min (optimised cutoff ≥ 0.675, p < 0.001), whereas TBR was not prognostic (p = 0.48). Multivariable Cox regression confirmed median SUV_max as independent of ILD-GAP index (p = 0.031), although optimised SUV_min was not independent. Incorporating either parameter into a modified ILD-GAP model improved survival stratification compared with ILD-GAP index alone (p < 0.01, log-rank test). High pulmonary [¹⁸F]FDG PET/CT uptake predicts increased mortality in NSIP. Median SUV_max is an independent predictor of mortality and adding [¹⁸F]FDG PET/CT parameters to the ILD-GAP index enhances prognostic discrimination. These findings support a disease-specific interpretation of [¹⁸F]FDG PET/CT metrics in ILD, where SUV_max and SUV_min are dominant prognostic markers in diffuse NSIP.