Novel PET approach identifies early signs of pulmonary arterial hypertension

PAH is a progressive and life-threatening disease in which the blood pressure in the pulmonary arteries (those that carry blood from the heart to the lungs) is abnormally high. This is often because the structure of the arteries is narrowed or damaged due to tissue remodeling.

"We know that during the remodeling process fibroblasts are activated," said Cheng Hong, MD, PhD, pulmonary vascular medicine specialist at the First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, in Guangzhou, China. "While PAH has traditionally been evaluated through hemodynamic measurements and echocardiography, my colleagues and I sought to determine if imaging the fibroblast activation protein could predict PAH disease progression."

The study included both preclinical and clinical components. In a small animal model, 15 rats were induced with PAH and five were designated to a control group. On days seven, 14 and 21, the rats were imaged with ¹⁸F-FAPI PET and hemodynamic measurements were recorded. Changes in ¹⁸F-FAPI uptake and hemodynamics over this time frame were compared.

In the human model, 38 patients with PAH underwent ¹⁸F-FAPI PET imaging, with right heart catheterization and echocardiography performed within one week to assess pulmonary hemodynamics and cardiac function. Treatment response was also assessed for patients who received PAH-targeted therapy.

Increased ¹⁸F-FAPI uptake in the right side of the heart and pulmonary arteries was associated with hemodynamics and cardiac function. Among the five patients who underwent PAH-targeted treatment, three demonstrated reduced ¹⁸F-FAPI uptake after receiving a second ¹⁸F-FAPI scan, which correlated with clinical improvement.

"The ability to detect fibroblast activation in PAH patients is significant as it could provide an early marker of disease progression, potentially before irreversible structural changes occur," stated Xinlu Wang, MD, PhD, nuclear medicine specialist at the First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine in Guangzhou, China.

"At the same time, we found that after PAH-targeted therapy, the uptake of ¹⁸F-FAPI in the right heart and pulmonary artery of patients decreased, suggesting the potential reversibility of fibroblast activation in PAH. ¹⁸F-FAPI PET could assist clinicians in monitoring the efficacy of PAH-targeted therapies, offering a new tool for personalized medicine."