Summary: A new imaging technique, 18F-FAPI PET, detects early fibroblast activation in pulmonary arterial hypertension, providing an early marker of disease progression and offering potential for personalized treatment and monitoring therapy response.
Key Takeaways
- Early Detection of PAH Progression: The 18F-FAPI PET imaging technique identifies fibroblast activation and tissue remodeling, offering an early marker for pulmonary arterial hypertension (PAH) progression before irreversible structural changes occur.
- Clinical and Preclinical Validation: Increased 18F-FAPI uptake in both animal and human models correlated with pulmonary hemodynamics and cardiac function, demonstrating its effectiveness in detecting and monitoring PAH.
- Potential for Personalized Treatment: The study showed that reduced 18F-FAPI uptake after PAH-targeted therapy correlates with clinical improvement, highlighting its role in evaluating treatment response and guiding personalized care.
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A new molecular imaging technique—18F-FAPI PET—can detect the first signs of tissue remodeling in patients with pulmonary arterial hypertension (PAH), providing physicians with an early marker for disease progression. This approach has the potential to pave the way for more personalized management of PAH, offering more timely interventions to improve patient prognosis.
Targeting Early PAH Detection
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,” says 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 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.
PET Tool Tracks PAH Therapy Effectiveness
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,” says 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,” Wang adds. “18F-FAPI PET could assist clinicians in monitoring the efficacy of PAH-targeted therapies, offering a new tool for personalized medicine.”
Featured image: Representative images of 18F-FAPI PET/CT at baseline and follow-up (A) A 58-year-old female patient with idiopathic PAH exhibited no improvements after 7 months of dual PAH-targeted drug therapy. The follow-up 18F-FAPI PET/CT demonstrated an increased uptake of 18F-FAPI in the RVOT, RV, LV and subsegmental PAs compared to baseline (arrows). (B) A 23-year-old male patient with idiopathic PAH exhibited significant improvements after 3 months of triple PAH-targeted drug treatment. The follow-up 18F-FAPI PET/CT results showed a decreased 18F-FAPI uptake in the RA, RV, RVOT, and proximal PAs compared to baseline (arrows). RVOT: RV outflow tract; RA: right atrium; LV: left ventricle.