18F-FAPI-74 Positron Emission Tomography/Computed Tomography Noninvasively Monitoring the Fibrosis of Cardiac Allograft Vasculopathy.

BACKGROUND

Cardiac allograft vasculopathy (CAV) is the primary cause of limited long-term survival among heart transplant recipients. This study aimed to evaluate the feasibility of 18F-FAPI-74 positron emission tomography/computed tomography (PET/CT) imaging for monitoring the fibrosis of CAV.

METHODS

Rat models of CAV were established and 1 hour dynamic PET/CT imaging was performed in the 15th week postoperation. Serial static 18F-FAPI-74 PET/CT imaging in the allograft and isograft groups were performed from week 3 to 17. Blocking experiments were performed on allograft rats to confirm the tracer's targeting specificity. In vivo PET/CT imaging findings were further corroborated by ex vivo PET/CT imaging and biodistribution studies. Histological examination was conducted to validate the model's effectiveness, and the correlation between FAP expression levels and imaging results was ascertained.

RESULTS

Dynamic PET/CT imaging revealed peak graft heart (Ht) uptake in the allograft group at 60 minutes post 18F-FAPI-74 injection. PET/CT imaging and biodistribution studies at all time points confirmed significantly higher radioactivity uptake in Ht of the allograft group, as compared with both their native hearts and Ht of the isograft group, and peaking at week 15. There was almost no radioactive accumulation of Ht in the allograft rats blocked by FAPI. Histological analysis confirmed significantly elevated FAP expression in Ht of the allograft group compared with the isograft group, consistent with the severity of CAV.

CONCLUSIONS

We successfully achieved molecular imaging of activated fibroblasts in CAV rat models, indicating that 18F-FAPI-74 PET/CT may be a valuable means of evaluating fibrosis progression of CAV.