[18 F] -FAPI-42 PET/CT assessment of Progressive right ventricle fibrosis under pressure overload

Background Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF.Methods Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18 F-labelled FAP inhibitor-42 ([(18) F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively.Results RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [(18) F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB.Conclusion RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [(18) F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.

Automated summary

The aim of this study was to develop effective approaches for early diagnosis and precise evaluation of right heart failure (RHF). Various tests were performed on rats with right ventricle pressure overload, including echocardiography, right heart catheterization, histological staining, etc. The results showed that RV function progressively declined and fibrosis occurred. RNA sequencing revealed gene changes caused by pressure overload and immunofluorescence indicated FAP as a marker for fibrosis. PET/CT was found to be as sensitive and accurate as histopathology in evaluating RV fibrosis.