99mTc-Labeled FAPI SPECT and 18F-FDG PET Imaging for Visualization and Evaluation of Connective Tissue Disease-associated Interstitial Lung Disease

Abstract 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 the active fibrotic process and ¹⁸F-FDG imaging for visualizing the 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 intense tracer uptake on 99mTc-HFAPI imaging, whereas most patients showed slight or mild tracer uptake on¹⁸F-FDG imaging. 8 patients showed severe uptake in both scans. 15 patients showed slight or mild ¹⁸F-FDG uptake but severe 99mTc-HFAPI uptake. No instances of severe ¹⁸F-FDG uptake coupled with low 99mTc-HFAPI uptake were observed among these 54 patients. When comparing the 99mTc-HFAPI parameters and pulmonary function testing (PFT) results, 99mTc-HFAPI uptake showed significantly negative correlation 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 the 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. Combining 99mTc-HFAPI with ¹⁸F-FDG imaging enables concurrent visualization and differentiation of fibrotic and inflammatory processes, potentially informing personalized management strategies.