Perfusion characteristics of a coronary artery ligation model in mice using Tc-99m-MIBI/SPECT and N-13-ammonia/PET

1534 Objectives: Myocardial perfusion assessment using nuclear imaging techniques is a standard radiologic practice in the clinical management of myocardial infarction (MI). However, very little work has been done to characterize myocardial distribution of commonly used perfusion tracers in mouse models of MI. The non-invasive and sensitive nature of nuclear procedures are sought after characteristics in drug development research; application of PET and/or SPECT in advancing stem cell and anti-oxidant therapy as well as organ transplant will be of immense significance. Here we describe the use of Tc-99m-Sestamibi (MIBI) and N-13-ammonia in a mouse model of left anterior coronary artery ligation (LAD ligation) for rapid and non-invasive characterization of ligation success and extent of injury. Methods: CD-1 mice (20-30 g) were anesthetized with isoflurane, endotracheally intubated, and ventilated. An incision was made on the left distal rib space, and the ribs were retracted above the left ventricle. A suture (8.0 nylon) was placed under the left anterior descending coronary artery and tied to restrict blood flow to the left ventricle. The ribs were approximated and sutured in place and the incision was closed. The mice were allowed to recover for 3 hours before imaging. Helical SPECT (24 projections of 45 s duration) was acquired of thoracic region by BioScan NanoSPECT In vivo Animal Imager at 1 h after injecting 74 MBq of MIBI in the tail vein (100-150 µL). PET acquisition was done on a Gamma Medica Ideas FLEX XO XPET PreClinlical Platform. PET was performed immediately after injecting approximately 8 MBq of N-13-ammonia in the tail vein (150 µL). For anatomical landmarks, whole body CT followed both SPECT and PET acquisitions. Infarct area was confirmed with Evans blue and TTC staining post-euthanasia. Results: Although non-gated nature of image acquisition resulted in significant loss of resolution, both Tc-99m-MIBI and N-13-ammonia showed a clear perfusion defect in the infarct area. Infarct delineation by MIBI/SPECT was better than that by N-13-ammonia/PET, which could be attributed to the difference in the spatial resolution of the cameras or residual blood pool activity at the imaging timepoints. The magnitude of image-derived perfusion deficit closely correlated with histologic assessment of infarct on Evans blue- and TTC-stained short axis heart slices. Conclusions: Small animal SPECT and PET have the resolution and sensitivity to assess myocardial perfusion in mouse model of MI. As such these techniques could be employed for non-invasive characterization of this standard model which is widely used in drug development research.