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

Abstract

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 (¹⁸FLT) 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 ¹⁸FLT-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. ¹⁸FLT-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 ¹⁸FLT k3 phosphorylation among pulmonary arterial hypertension patients, unaffected bone morphogenetic protein receptor type 2 mutation carriers and healthy controls. Lung ¹⁸FLT uptake did not correlate with haemodynamic or clinical parameters in pulmonary arterial hypertension patients. Sequential ¹⁸FLT-PET scanning in three patients demonstrated uneven regional distribution in ¹⁸FLT 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 ¹⁸FLT 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 ¹⁸FLT report may be explained by a small sample size previously and we observed large variation of lung ¹⁸FLT signals between patients, challenging the application of ¹⁸FLT-PET as a biomarker in the pulmonary arterial hypertension clinic.

Keywords: clinical diagnosis; clinical outcome; pathogenesis; pulmonary hypertension.