99mTc-Labeled FAPI SPECT and 18F-FDG PET imaging for visualization and evaluation of connective tissue disease-associated interstitial lung disease.

BACKGROUND: The pathogenesis of connective tissue disease-associated interstitial lung disease (CTD-ILD) involves complex interactions between inflammatory cell infiltration and fibroblast activation, which are pivotal in driving the disease progression. The aim of the study was to assess the feasibility of 99mTc-HFAPI imaging for visualizing active fibrotic process and 18F-FDG imaging for visualizing inflammatory process in CTD-ILD patients. RESULTS: A total of 54 CTD-ILD patients were enrolled. Visual analysis revealed that nearly half of the patients exhibited high tracer uptake on 99mTc-HFAPI imaging, whereas most patients showed low or moderate uptake on 18F-FDG imaging. 8 patients showed high uptake in both scans. 15 patients showed low or moderate 18F-FDG uptake but high 99mTc-HFAPI uptake. No patients demonstrated high 18F-FDG uptake coupled with low 99mTc-HFAPI uptake were observed among these 54 patients. Correlation analysis between 99mTc-HFAPI parameters and pulmonary function testing (PFT) results showed 99mTc-HFAPI uptake was significantly negatively correlated with forced vital capacity (FVC) [whole lung (wl) SUVmean: R=-0.45, p < 0.005; metabolic active volume (MAV): R=-0.41, p < 0.005; total lesion (TL): R=-0.45, p < 0.005] and diffusion capacity for carbon monoxide (DLCO) (wlSUVmean: R=-0.58, p < 0.005; MAV: R=-0.62, p < 0.005; TL: R=-0.65, p < 0.005). Significantly positive correlations were observed between 99mTc-HFAPI parameters and disease extent on HRCT (wlSUVmean: R = 0.51, p < 0.005; MAV: R = 0.53, p < 0.005; TL: R = 0.64, p < 0.005). In contrast, 18F-FDG parameters demonstrated weak or mild correlations with both PFT results and disease extent on HRCT. CONCLUSION: 99mTc-HFAPI imaging shows promising utility in assessing active fibrosis in CTD-ILD patients, demonstrating superior performance over 18F-FDG. The potential added value of dual-tracer imaging for characterization fibrotic and inflammatory processes might provide more insights of CTD-ILD.