PET Imaging Could Help Track PAH Onset, Therapy Response, Study Finds

A new type of molecular imaging may help quickly identify the first signs of pulmonary arterial hypertension (PAH) and make it easier for clinicians to track disease progression and therapeutic response.

A study from the Journal of Nuclear Medicine suggests that the use of F-labeled fibroblast activation protein inhibitors in positron emission tomography (F-FAPI PET) may be a useful and less invasive diagnostic tool in PAH.

Right heart catheterization has long been considered the gold standard of PAH diagnosis. Yet, its invasive nature has proven a hurdle to early diagnosis of the disease. That’s important because studies have repeatedly shown that delayed diagnoses of PAH lead to inferior outcomes.

For instance, a study published last year in the Journal of Cardiology found that patients who were diagnosed within the first three months of symptom onset were more likely to be in low- and moderate-risk groups and also had lower rates of PAH events compared with those whose diagnoses were delayed at least three months after symptom onset.

Cheng Hong, M.D., Ph.D., pulmonary vascular medicine specialist at the First Affiliated Hospital of Guangzhou Medical University in China, is one of the authors of the new study. Hong said one way to boost early diagnosis would be to find easier ways of diagnosing the disease.

“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 progression,” Hong said in a press release.

Hong explained that heightened activation of adventitial fibroblasts in the pulmonary artery contributes to vascular remodeling, which in turn leads to right ventricle (RV) afterload, cardiac dysfunction, and PAH progression. Cardiac fibroblast activation is an early sensor of environment stress and accelerates as the disease takes hold, they noted.

Hong and colleagues wondered whether the use of imaging to track fibroblast activation might allow clinicians to catch the disease more quickly and perhaps take action to prevent irreversible pulmonary arterial remodeling.

Over the past three years, a handful of studies have looked at the use of radionuclide-labeled FAPIs in imaging the right ventricle and pulmonary artery in the context of chronic thromboembolic pulmonary hypertension. The findings of the 2023 study have shown the technique to be feasible.

Yet, Hong said the idea of using FAPI PET imaging as an early detection tool for PAH has to date been unexplored. Hong and his colleagues used both preclinical and clinical methods to evaluate F-FAPI PET. First, they imaged 15 rats with monocrotaline-induced PAH at seven, 14, and 21 days after injection. Hemodynamic measurements were recorded at the same time intervals. Those 15 rats were compared with five healthy controls.

The investigators found that right ventricle systolic pressure in the PAH group increased between days 14 and 21, while F-FAPI uptake and fibroblast activation protein expression in the myocardium and lungs peaked at 14 days, they said.

Next, Hong and colleagues turned to human patients with PAH. Thirty-eight patients were recruited and underwent both F-FAPI PET imaging, right heart catheterization, and echocardiography within a one-week time frame. The investigators found that F-FAPI uptake in the myocardium and proximal and distal pulmonary arteries correlated with clinical indicators, right ventricle function, and pulmonary hemodynamic parameters.

Five patients who were taking PAH-targeted therapy were given a second scan after several months on therapy. Three of those patients had F-FAPI changes matching clinical improvement.

“We found that after PAH-targeted therapy, the uptake of F-FAPI in the right heart and pulmonary artery of patients decreased, suggesting the potential reversibility of fibroblast activation in PAH,” Hong and colleagues wrote.

The investigators believe this suggests that F-FAPI PAH could provide a new tool with which to monitor patients.

“F-FAPI could assist clinicians in monitoring the efficacy of PAH-targeted therapies, offering a new tool for personalized medicine,” Hong said in the statement.

The investigators cautioned that their sample size was small, and thus the results would need to be replicated in a larger patient population. In addition, they noted that the thin pulmonary artery wall rendered the standard uptake value (SUV) measurement susceptible to partial-volume effects.

“Although we used a high-resolution PET imaging protocol to minimize the influence of partial volume effects, it remains a critical factor to consider when interpreting our results,” the authors wrote.