Dual-tracer FDG and FAPI PET imaging for dynamic monitoring and early detection of chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of late mortality after lung transplantation, yet current diagnosis mainly depends on lung function decline. We investigated whether dual-tracer positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) and fibroblast activation protein inhibitor (FAPI) could noninvasively characterize the transition from inflammation to fibrosis during CLAD progression. Using a rat orthotopic lung transplantation model with longitudinal PET/CT from weeks 1 to 6, findings were correlated with histopathology, immune infiltration, cytokines, fibroblast activation, and collagen deposition. Clinical PET/CT data from transplant recipients were also analyzed. Histology showed progressive airway remodeling and fibrosis. FDG uptake peaked at week 3, matching CD8+/CD19+ infiltration and IL-6 expression. FAPI uptake rose later, linking to fibroblast activation and matrix deposition. Thus, FDG and FAPI revealed distinct inflammatory and fibrotic phases. Clinically, abnormal dual-tracer uptake appeared in a recipient before lung function met CLAD criteria, while a stable recipient showed no abnormal signal. These findings may help advance the early diagnosis, biological staging, and individualized clinical management of CLAD.