Exploring the Potential Value of [68Ga]Ga-FAPI-46 PET/CT for Molecular Assessment of Fibroblast Activation in Interstitial Lung Disease
Authors: Bahtouee Mehrzad , Jafari Esmail , Khazaei Mehdi , Aram Nahid , Amini Azam , Jokar Narges , Ahmadzadehfar Hojjat , Gholamrezanezhad Ali , Assadi Majid 
Published: October 2024

Background
The aim of the study was to evaluate the association of high-resolution computed tomography (HRCT) findings with pulmonary fibrotic activity in the corresponding regions using [68Ga]Ga–fibroblast activation fibroblast inhibitor (FAPI) PET/CT in patients with interstitial lung disease (ILD). Additionally, the potential of [68Ga]Ga-FAPI-46 PET/CT for evaluating the active fibrosis process and 99mTc-MIBI scintigraphy for assessing the inflammatory process in ILD patients was also assessed.

Methods
In this pilot study, 20 ILD patients underwent [68Ga]Ga-FAPI-46 PET/CT and 99mTc-MIBI SPECT/CT. Additionally, 10 patients without lung or thoracic involvement who were undergoing [68Ga]Ga-FAPI PET/CT for cancer detection were enrolled in the control group. The images were evaluated both visually and semiquantitatively and also compared with HRCT and pulmonary function tests. Multiple quantitative parameters were derived from the lung segments in the PET scan, including SUVmax, SUVmean, maximum target-to-liver ratio, mean target-to-liver ratio (TLRmean), and total lesion FAPI expression for the entire lung, as well as its lobes and zones. Additionally, the maximum Hounsfield unit (HU) and mean HU in HRCT were calculated for the whole lung as well as its lobes and zones. Furthermore, an HRCT fibrosis score (HFS) was defined according to the HRCT findings.

Results
Twenty ILD patients with a mean age of 58.70 (SD, 11.09) years were enrolled. Additionally, 10 control patients were enrolled with a mean age of 57.70 (SD, 15.19) years. Based on visual assessment, the FAPI scan was positive in 12 (60%) patients. Similarly, the MIBI scan was positive in 12 (60%) patients. In the 20 ILD cases, both scans were positive in 6 cases, and both were negative in 2 cases. Six cases showed FAPI-negative and MIBI-positive results, whereas another 6 cases showed FAPI-positive and MIBI-negative results. Comparing the control and ILD patients, there was a significant difference in SUVmax, SUVmean, total lesion FAPI expression, TLRmean, maximum HU, and mean HU (P < 0.05). When comparing HFS with PET-derived parameters in zones, a significant positive correlation was found between HFS and SUVmean, SUVmax, maximum target-to-liver ratio, and TLRmean (P < 0.05). Additionally, a significant difference was noted between FAPI results and HFS (P = 0.003). An ancillary finding, 9 of 20 (45%) ILD patients showed intense FAPI uptakes in gallbladder, whereas none of the 10 in the control group showed such uptake.

Conclusion
The present study may suggest that combining [68Ga]Ga-FAPI PET/CT and 99mTc-MIBI SPECT/CT yields an additive effect for evaluating ILD-related fibrosis and inflammatory processes over using either modality alone. Furthermore, it appears that [68Ga]Ga-FAPI PET/CT has the potential to ascertain levels of fibrotic activity from population of resident fibroblasts, active fibroblasts, and scar maturation among ILD patients based on their HRCT patterns.