[18F]FDG PET signal correlates with markers of neo-angiogenesis in patients with fibrotic interstitial lung disease who underwent lung biopsy: Implication for the use of PET/CT in diffuse lung diseases

Abstract

Purpose The potential to use FDG PET/CT in diffuse lung diseases is becoming increasingly recognised. To understand the potential of the technique better, we investigated the correlation between [18F]FDG lung uptake with microvessel density (MVD) on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods We recruited 18 patients with fILD who underwent [18F]FDG PET before lung biopsy. We derived target-to-background ratio (TBR) of maximum pulmonary uptake of FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded sections obtained from biopsy were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD; CD31 and CD105/ endoglin) and glucose transporter 1 (GLUT-1). MVD was expressed as vessel area % per high-power field (Va%/hpf); Statistical analysis was carried out using SPSS. Results 18 patients were followed for an average of 41.36 months (range 5.69-132.46 months; median 30.07 months). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with low CD105-MVD (score of < 12 Va%/hpf) and/or low CD31-MVD (score of < 34 Va%/hpf) had a significantly better prognosis (no deaths during follow-up) than patients with higher scores of CD105-MVD (median survival < 35 months, p = 0.041, n = 13) or CD31-MVD (median survival < 30 months, p = 0.037, n = 13). However, only CD105-MVD showed a significantly positive correlation with [18F]FDG TBR (rs = 0.556, p < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of GLUT-1. Conclusion Previous work has used FDG-PET as a biomarker in fILD. Here we highlight a correlation between angiogenesis and FDG TBR, both of which predict mortality in patients with fILD. These data set the scene to investigate the potential role of the vasculature and angiogenesis in fibrosis.

Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting

“…17 18 We have previously shown that FDG uptake on PET/CT is a prognostic biomarker in IPF 19 and showed TBR to be predictive of 3 year mortality. In patients with fibrotic ILD, we have observed that TBR correlates with neoangiogenesis markers, 20 and in patients with NSIP we observed that a high pulmonary background signal (SUVmin) negatively correlated with mortality. 21 Others have investigated the utility of FDG uptake in ILD subtype differentiation 22 and in determining disease activity in ILDs associated with rheumatological conditions.…”

“…19 More recently, we have also shown TBR to correlate with biomarkers of new vessel angiogenesis, which itself is predictive of poorer survival. 20 In 27 patients with IPF, SUVmax was shown to be predictive of FVC, TLCO and physiological decline at 12 months. 18 A larger study of 89 patients reported baseline SUVmax to be predictive of TLCO decline at 6 months, but no relationship was observed with survival outcomes.…”