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In Vivo Detection of Stem Cells Grafted in Infarcted Rat Myocardium

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

The evaluation of stem cell–mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of ^99mTc-sestamibi to assess myocardial perfusion and of ¹¹¹In-labeled stem cells to delineate stem cell engraftment. Methods: Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1–14.8 MBq (0.3–0.4 mCi) of ¹¹¹In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. ¹¹¹In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of ^99mTc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image ^99mTc-sestamibi uptake simultaneously with ¹¹¹In to delineate retention of ¹¹¹In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. Results: SPECT of ^99mTc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull’s-eye plots indicated that the ¹¹¹In signal from the labeled stem cells overlapped the perfusion deficits identified from the ^99mTc-sestamibi images. The ¹¹¹In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. Conclusion: This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with ^99mTc-sestamibi and with ¹¹¹In-labeled stem cells grafted into the region of the infarct.

Key Words: myocardium • ischemia • stem cells • indium • sestamibi • SPECT

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