PET Imaging in Pulmonary Hypertension

Pulmonary hypertension comprises a heterogeneous group of diseases characterized by elevated pulmonary arterial pressures and progressive right ventricular (RV) remodeling, with RV failure as the principal determinant of outcome. This review discusses positron emission tomography (PET) imaging across pulmonary hypertension, with particular emphasis on pulmonary arterial hypertension, in which pulmonary vascular remodeling and RV adaptation are central disease features. Although echocardiography and cardiac magnetic resonance imaging provide robust assessment of RV structure, function, and fibrosis, they are limited in detecting early molecular alterations that precede overt dysfunction. PET offers a unique opportunity to visualize these processes. In particular, [¹⁸F]fluorodeoxyglucose PET has demonstrated a shift in RV substrate utilization from fatty acid oxidation toward glycolysis, reflecting metabolic stress and maladaptation. More recently, fibroblast activation protein inhibitor PET has emerged as a promising modality, with first-in-human studies in pulmonary arterial hypertension demonstrating uptake in the RV and pulmonary vasculature, consistent with active remodeling. Beyond fibroblast activation, additional metabolic and immunologic targets may provide complementary insight into pulmonary vascular disease activity, RV remodeling, and treatment response. Together, these advances position PET as a powerful tool for early detection, phenotyping, and risk stratification in pulmonary hypertension, with particular relevance for pulmonary arterial hypertension.