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In Vivo Detection of Stem Cells Grafted in Infarcted Rat Myocardium

Rong Zhou, PhD1, Daniel H. Thomas, MD1, Hui Qiao, PhD1, Harshali S. Bal, BS1, Seok-Rye Choi, PhD1, Abass Alavi, MD1, Victor A. Ferrari, MD1,2, Hank F. Kung, PhD1,3 and Paul D. Acton, PhD1

1 Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
2 Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
3 Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania



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FIGURE 1. Cardiac long- and short-axis SPECT images of normal (A and C) and infarcted (E and G) heart using perfusion tracer 99mTc-sestamibi. 111In signal (color) was overlaid on gray-scale 99mTc-sestamibi images for normal (B and D) and infarcted (F and H) heart.

 


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FIGURE 2. Bull’s-eye plots of 99mTc-sestamibi signal (A, C, and E) and 111In signal (B, D, and F) from normal rat (rat 3) and 2 rats with different infarction sizes (rats 2 and 4). Color bar represents transition from weak to strong signal intensity from left to right.

 


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FIGURE 3. Time course of background 111In signal intensity in region of lungs and thorax in rats 3 (top) and 4 (bottom). Each image was normalized to give same maximum count to show relative washout of tracer from thoracic cavity. Signal detected in thoracic region in rat 3 in first image (acquired within 2 h after injection) was likely due to some leakage during injection of cells.

 


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FIGURE 4. Time course of 111In signal intensity in hearts from 6 animals. Curve was corrected for radioactive decay of 111In. Error bars represent 1 SD.

 


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FIGURE 5. (A and B) Autoradiographs (left) of 3 adjacent slices and corresponding photographs (right). Region of intense 111In uptake (boxed area) was identified on each slice. (C and D) Histologic analysis of adjacent tissue slices reveals injected cells localized in region outlined in box. SPIO particles (arrowheads) are stained blue, whereas nuclei (short arrows) are counterstained red. Magnified view (D) of boxed area in C shows intensely SPIO-labeled cells (e.g., 1 in center) and slightly labeled cells (e.g., 1 in right corner, which contained only 1 blue dot; the cell is round, as delineated by pink-stained cytoplasm, and has a large nucleus). Unique morphology distinguishes injected cells from surrounding myocardium. Bundle of muscle fibers (long arrows) is also seen. LV = left ventricle; RV = right ventricle.

 





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