Abstract 17020: Molecular Spect Imaging of Early Angioproliferative Group I Pulmonary Arterial Hypertension Using an Adrenomedullin Receptor Ligand
Introduction: The main limitation in the development of drugs against pulmonary arterial hypertension (PAH) is the absence of a non-invasive and early marker of disease. Adrenomedullin (AM) is a vasodilator peptide predominantly cleared by pulmonary endothelial receptors.
Hypothesis: Our lab has developed Pulmobind "PB", an AM derivative radiolabeled with 99mTc for SPECT imaging of pulmonary circulation to detect non-invasively the anomalies of pulmonary circulation caused by PAH.
Methods: An angioproliferative model of group I PAH was used. After a single subcutaneous injection of the vascular endothelial growth factor receptor blocker "Sugen" (20 mg/kg), rats were exposed to hypoxia for 3 weeks followed by normoxia for 4 weeks. PAH rats were compared to their littermate controls (normoxia for 7 weeks). After 7 weeks, Right ventricular (RV) structure, function and hypertrophy as well as lung 99mTc-PB uptake kinetics were assessed by echocardiography and SPECT analyses.
Results: RV end-diastolic anterior wall thickness and RV weight ratio (RV/LV) were significantly increased in PAH rats compared to controls (+54% and +24%; p<0.0001, respectively). Pulmonary artery acceleration time, (PAAT, an index of pulmonary artery pressure) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased (-16%; p<0.0001 and -7%; p<0.01, respectively). Mean pulmonary uptake of 99mTc-PB was lower in PAH rats. Integrated pulmonary % activity-time curve from the 1st to 30 minutes after injection was significantly lower in PAH rats compared to controls (-19.2%; p<0.05).
Conclusion: This preliminary data demonstrate the feasibility of using 99mTc-PB for molecular imaging of angioproliferative group I PAH. The results suggest a reduction in the pulmonary AM receptor activity and/or density as early as 7 weeks after initial injury.
Author Disclosures: N. Merabet: None. Q. Trinh Nguyen: None. S. Marcil: None. B. Meloche: None. Y. Fen Shi: None. J. Tardif: None. F. Harel: None. J. Dupuis: None.
- © 2014 by American Heart Association, Inc.