Abstract 2101: Molecular Imaging Of Pulmonary Arterial Hypertension With Radiolabeled Linear Adrenomedullin
BACKGROUND. Pulmonary arterial hypertension (PAH) is associated with endothelial dysfunction. Adrenomedullin (AM) is a vasodilator peptide predominantly cleared by the pulmonary circulation through specific endothelial receptors. We developed a linear human AM derivative (AM-L) enabling direct radiolabeling with 99mTc and external imaging of the pulmonary vascular endothelium using a gamma camera. We evaluated the use of 99mTc-AM-L in the detection of PAH.
METHODS. PAH was induced by the injection of monocrotaline in rats (n=5) and compared to sham treated animals (n=5). After 5 weeks the animals were anesthetized and ~700 μCi of 99mTc-AM-L injected intravenously. Blood samples were obtained to evaluate plasma kinetics of the tracer and lung activity was determined after 30 min, in vivo using a gamma camera and ex vivo by counting the activity of explanted lungs.
RESULTS. 99mTc-AM-L was rapidly cleared from plasma following a two-compartment model. The plasma distribution half-life was increased in PAH form 1.1 to 1.4 min resulting in ~2 fold higher plasma levels after 10 minutes (p=0.03). The tracer uptake by the lungs was homogeneous but greatly reduced in PAH by about ~70% compared to controls. The activity retained by the lungs as determined by the gamma camera in vivo was 4 ± 1% of the injected dose (ID) in PAH compared to 14 ± 1 % in controls, p < 0.0001. A similar reduction of uptake was observed by ex vivo evaluation of explanted lungs (3 ± 1% ID vs. 11 ± 2% for PAH vs. controls, p < 0.001).
CONCLUSION. Pulmonary uptake of the molecular tracer 99mTc-AM-L is greatly reduced in PAH and can be detected using external imaging with a gamma camera. This novel molecular imaging agent may be useful in the diagnosis and follow up of PAH.