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 ^99m Tc-HFAPI imaging for visualizing the active fibrotic process and ¹⁸ F-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 ^99m Tc-HFAPI imaging, whereas most patients showed slight or mild tracer uptake on ¹⁸ F-FDG imaging. 8 patients showed severe uptake in both scans. 15 patients showed slight or mild ¹⁸ F-FDG uptake but severe ^99m Tc-HFAPI uptake. No instances of severe ¹⁸ F-FDG uptake coupled with low ^99m Tc-HFAPI uptake were observed among these 54 patients. When comparing the ^99m Tc-HFAPI parameters and pulmonary function testing (PFT) results, ^99m Tc-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 ^99m Tc-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, ¹⁸ F-FDG parameters demonstrated weak or mild correlations with both PFT results and disease extent on HRCT. Conclusion ^99m Tc-HFAPI imaging shows promising utility in assessing active fibrosis in CTD-ILD patients. Combining ^99m Tc-HFAPI with ¹⁸ F-FDG imaging enables concurrent visualization and differentiation of fibrotic and inflammatory processes, potentially informing personalized management strategies.