Page 132 - Assessing right ventricular function and the pulmonary circulation in pulmonary hypertension Onno Anthonius Spruijt

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Few studies have explored the application of PET imaging in PAH. Previously we have reported on 18FDG‐PET as a tool for following response to treatment in animal models and the signal from patients with PAH, but this ligand reports on both proliferation and inflammation. Here we evaluate the potential of 18FLT PET as an imaging biomarker for assessing the distinctive hyper‐proliferative pulmonary vascular pathology seen in PAH. First, we examined 18FLT lung uptake in idiopathic PAH (IPAH) patients in comparison to control subjects. Second, we assessed whether 18FLT PET could track pulmonary pathology in animal PAH models and their response to targeted therapies. Third, we examined ENT1 and TK1 expression in lung tissues and pulmonary vascular fibroblasts isolated from IPAH patients to understand the drivers of lung 18FLT uptake in PAH.
Methods
Patient population
8 patients (Table 1) diagnosed with IPAH according to ERS guidelines [23] were recruited from the VU University Medical Center; both treatment naive and treated patients were included in this study. We made use of 18FLT PET data sets from an oncology study of non‐small cell lung cancer patients [24] from the VU University Medical Center as controls. We included 6 subjects who had confirmed one‐sided lung tumor; 18FLT PET data from the tumor‐free side of the lung was used as control for comparison with IPAH patients. The study was approved by the Medical Ethical Review Committee of the VU University Medical Center (Toetsingonline: NL49166.029.14) and all IPAH patients gave written informed consent.
Right heart catheterizations and cardiac magnetic resonance imaging
All patients underwent right heart catheterization and cardiac magnetic resonance imaging (CMR) within one month of their PET/CT scan, and in this period all patients were stable on pulmonary hypertension targeted therapy. A balloon‐tipped, flow‐directed 7.5F, triple‐lumen Swan‐Ganz catheter (Edwards Lifesciences LLC, Irvine, CA) was inserted in the pulmonary artery via the jugular vein or femoral vein under local anesthesia and constant ECG monitoring, and measurements were performed according to guidelines [23]. Catheter ports were placed in the right atrium, right ventricle and pulmonary artery and the zero reference level for the pressure transducer was placed at mid‐thoracic level in supine position.