A new study has found that preclinical positron emission tomography (PET) imaging using [18F]-2-fluoro-2-deoxy-D-glucose to detect pulmonary arterial hypertension (PAH) is a promising approach.

The study, published in EJNMMI Research, employed 2 tracers to target activin receptor-like kinase 5 (ALK5), which is signaled by the cytokine transforming growth factor β (TGFβ).

The research team used a monocrotaline Wistar rat model and a Sugen/hypoxia Sprague Dawley rat model of PAH to investigate the use of preclinical PET imaging of ALK5. The aim was to develop a noninvasive diagnostic biomarker for PAH. In both animal models, [18F]EW-7197 and [11C]LR111 were assessed as tracers to visualize ALK5 in the lungs.

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“Activation of the TGFβ/ALK5 pathway has been observed in pulmonary cells of remodeled pulmonary arteries of patients with idiopathic PAH,” the authors wrote. “This indicates that components of the TGFβ/ALK5 signaling pathway may provide potential biomarkers for early diagnosis and therapeutic evaluation of PAH.”

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The results showed that messenger RNA levels of ALK5 were notably higher in the lungs of both animal models than in healthy control lungs. ALK5 expression levels were higher in the Sugen/hypoxia-exposed lungs than in the monocrotaline-exposed lungs. ALK5 was found primarily in the endothelial and epithelial cells of the pulmonary arteries, as has been found in previous studies.

The authors observed significantly greater binding of the tracers to diseased lungs than to healthy ones, supporting their potential use as noninvasive diagnostic in vivo imaging candidates for ALK5 in PAH.

However, as a limitation, the team noted that the tracers were cleared in both animal models and returned to normal levels within 15 minutes, which might indicate that the tracer uptake was due to changes in lung perfusion and could impede their use as tracers in clinical settings of PAH.


Rotteveel L, Poot AJ, Kooijman EJM, et al. Imaging the TGFβ type I receptor in pulmonary arterial hypertension. EJNMMI Res. 2023;13(1):23. doi:10.1186/s13550-023-00966-7