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J Nucl Med. 2008; 49 (Supplement 1):184P
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Cardiovascular: Basic Science

Basic Science Posters

Genetic labeling of cardiac stem cells for in vivo monitoring of engraftment in ischemic myocardium

John Terrovitis1, Riikka Lautamäki1, Jianhua Yu1, Andreas Barth1, Martin Pomper1, Richard Wahl1, Benjamin Tsui1, M. Roselle Abraham1, Eduardo Marbán1 and Frank Bengel1

1 Johns Hopkins University, Baltimore, Maryland

802

Objectives: Cardiac-derived stem cells (CDCs) are attractive for regenerative myocardial therapy. To test cell survival and engraftment, we labeled CDCs genetically with a reporter gene for molecular imaging.

Methods: CDCs were isolated from syngeneic Wistar Kyoto rats and transduced with the sodium-iodide symporter gene (NIS) using lentiviral vectors. Transduction efficiency and transgene function were determined in vitro. For in vivo imaging, 2x106 labeled CDCs were injected intramyocardially in 14 infarcted rats (LAD ligation just prior to CDC injection). Dual isotope SPECT/CT imaging was performed one hour after injection of 7mCi of 99mTc-pertechnetate (for cell visualization) and 1mCi of 201Tl (for delineation of normally perfused myocardium).

Results: Transduction efficiency was >70%, assessed by immunocytochemistry. There were no adverse effects of NIS on CDC viability/proliferation. In vitro 99mTc uptake was high and specific in NIS CDCs (6.5% vs 0.1% when blocked by perchlorate). In all animals injected with NIS CDCs, dual- isotope small animal SPECT-CT at day 2 after cell injection showed focal 99mTc accumulation, indicating the presence of NIS expressing cells within the 201Tl perfusion defect. The origin of the 99mTc signal from the myocardium and not the blood pool was confirmed by ex vivo imaging. In 3 animals that underwent longitudinal imaging up to day 10 after cell injection, NIS expressing cells were identified up to day 4 in all three and up to day 6 in two.

Conclusions: Lentivirus mediated transduction of CDCs is feasible and effective allowing for radionuclide imaging of CDCs. Labeling of stem cells with NIS for SPECT has potential for translation to human imaging and may allow longitudinal cell tracking.

Research Support: Donald W Reynolds Foundation and NHLBI





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Right arrow Articles by Terrovitis, J.
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Right arrow Articles by Terrovitis, J.
Right arrow Articles by Bengel, F.