Abstract 3195: Quantification of Endothelial Cell Apoptosis in Pulmonary Arterial Hypertension Using Tc99m-Annexin V
Background- Pulmonary artery hypertension (PAH) is usually detected late in its course. Early detection may allow for the earlier initiation of disease-modifying therapies. Endothelial cell (EC) apoptosis is an early event that leads to unrestrained EC growth and subsequent smooth muscle cell proliferation. We tested the hypothesis that these early apoptotic changes may be detected non-invasively using Tc99m-labeled Annexin V (Tc99m-ANX) in the monocrotaline (MCT)-induced PAH rat model.
Methods- To document disease course, 54 MCT treated Sprague Dawley rats (60mg/kg) were compared to 18 controls; 5– 6 treated rats and 3 controls were sacrificed weekly over 6 weeks for gross pathology and histopathologic sectioning. PA pressures were estimated by echocardiography. EC apoptosis was detected by caspase staining in arterioles smaller than 50 microns and quantified by random sampling. A second group of 16 rats were treated with MCT and underwent serial non-invasive SPECT imaging. They were injected with 55.5 MBq of Tc99m-ANX and imaged by HiSPECT at baseline (before MCT) and weekly for 6 weeks. Quantification of Tc99m-ANX uptake was assessed by biodistribution and by region of interest (ROI) analyses of SPECT images using MIP Tool.
Results- See table⇓ below. Quantitative pulmonary tracer uptake peaked at day 14, correlated with peak positive caspase staining and preceded hemodynamic changes and RVH. Tc99m-ANX pulmonary uptake seen at later time points corresponded to caspase positive inflammatory cells in a dense intra-alveolar infiltrate.
Conclusions- EC apoptosis can be detected in vivo with Tc99m-ANX during the early development of PAH in MCT treated rats before the onset of any detectable changes in pulmonary pressures or changes in RV architecture.