In vivo imaging of atherosclerotic plaque growth in ApoE-/- Mice using

Tc99m-HYNIC-Annexin-V SPECT


A. Walz-Flannigan, S.P. Mok, Y. Wang, K. L. Gabrielson, J. Fox , C. Foss, S. Nimmagadda, M. Seshadri, M. G. Pomper, and B.M.W. Tsui

Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD



In our study, we wished to ascertain the feasibility of using a small animal SPECT/CT system with Tc99m-HYNIC-Annexin-V to identify and follow atherosclerotic lesions in ApoE-/- mice.


Transgenic ApoE-/- mice were fed a high fat and cholesterol diet starting from 5 weeks up to 41 weeks of age. During this time SPECT and CT image data were acquired from each animal at 3 to 4 time points between 18 and 41 weeks using a Gamma Medica-Ideas FLEX MicroSPECT/CT imager. The SPECT imaging system is equipped with dual modular cameras having 82x82 NaI(Tl) pixellated crystal elements and pinhole collimators with 1mm-aperture and 9cm focal length. The animals were first injected with ~2 to 7.5 mCi of Tc99m-HYNIC-Annexin-V through the tail vein. A total of 128 projection views with a magnification factor of about 3.5 were acquired over 360o with 20-30 sec/view. Images were reconstructed using a 3D iterative pinhole reconstruction method with correction of system misalignment parameters obtained for each date by calibration measurement and pinhole response function. The mice were sacrificed after the final scan and the aortas excised for gross pathology, autoradiography and histology.


SPECT/CT images show an increased uptake of Tc99m-HYNIC-Annexin-V at areas consistent with the development of atherosclerotic lesions in ApoE-/- mice. We observed an increase in uptake and number of atherosclerotic lesions over multiple scans. In at least one case we were able to follow a single lesion over three time points between 20 and 27 weeks of age and observe a change in its overall size or uptake. Later time points also exhibited an overall increase in the uptake of Tc99m-HYNIC-Annexin-V in the heart muscle and other organs. The aorta, carotid and pulmonary arteries, excised between 38 and 41 weeks, showed extensive plaque development throughout. Autoradiography confirmed the uptake of Tc99m-HYNIC-Annexin-V in the plaques.


We are able to detect atherosclerotic plaques in ApoE-/- mice and monitor their uptake of Tc99m-HYNIC-Annexin-V with current SPECT imaging equipment and techniques. These measurements are being used as a guide in continuing studies to correlate images with specific physiological changes and to develop high resolution SPECT imaging systems with quantitative image reconstruction methods.  

Research Support

 NIH grant # R01 EB1558.