Application of [18F]FLT-PET in pulmonary arterial hypertension: a clinical study in pulmonary arterial hypertension patients and unaffected bone morphogenetic protein receptor type 2 mutation carriers

• Main Authors: Liza Botros, Samara M.A. Jansen, Ali Ashek, Onno A. Spruijt, Jelco Tramper, Anton V. Noordegraaf, Jurjan Aman, Hans Harms, Frances S. de Man, Marc C. Huisman, Lan Zhao, Harm J. Bogaard
• Format: Article
• Language: English
• Published: SAGE Publishing 2021-06-01
• Series: Pulmonary Circulation
• Online Access: https://doi.org/10.1177/20458940211028017

Pulmonary arterial hypertension is a heterogeneous group of diseases characterized by vascular cell proliferation leading to pulmonary vascular remodelling and ultimately right heart failure. Previous data indicated that 3′-deoxy-3′-[18F]-fluorothymidine ( 18 FLT) positron emission tomography (PET) scanning was increased in pulmonary arterial hypertension patients, hence providing a possible biomarker for pulmonary arterial hypertension as it reflects vascular cell hyperproliferation in the lung. This study sought to validate 18 FLT-PET in an expanded cohort of pulmonary arterial hypertension patients in comparison to matched healthy controls and unaffected bone morphogenetic protein receptor type 2 mutation carriers. 18 FLT-PET scanning was performed in 21 pulmonary arterial hypertension patients (15 hereditary pulmonary arterial hypertension and 6 idiopathic pulmonary arterial hypertension), 11 unaffected mutation carriers and 9 healthy control subjects. In-depth kinetic analysis indicated that there were no differences in lung 18 FLT k3 phosphorylation among pulmonary arterial hypertension patients, unaffected bone morphogenetic protein receptor type 2 mutation carriers and healthy controls. Lung 18 FLT uptake did not correlate with haemodynamic or clinical parameters in pulmonary arterial hypertension patients. Sequential 18 FLT-PET scanning in three patients demonstrated uneven regional distribution in 18 FLT uptake by 3D parametric mapping of the lung, although this did not follow the clinical course of the patient. We did not detect significantly increased lung 18 FLT uptake in pulmonary arterial hypertension patients, nor in the unaffected bone morphogenetic protein receptor type 2 mutation carriers, as compared to healthy subjects. The conflicting results with our preliminary human 18 FLT report may be explained by a small sample size previously and we observed large variation of lung 18 FLT signals between patients, challenging the application of 18 FLT-PET as a biomarker in the pulmonary arterial hypertension clinic.