A method for quantitative cell tracking using SPECT for the evaluation of myocardial stem cell therapy.

Purpose: A promising SPECT-based method for evaluating stem cells therapy uses (111)In-labelled cells, transfected with a reporter gene. Cells are first transplanted to the infarct, and subsequently interrogated for transgenic expression using a systemic injection of an (131)I-labelled reporter probe. The method is impeded by the physical effects of scatter, (131)I/(111)In cross-talk, and attenuation. We hypothesize that correcting for physical effects improves detection of transgenic expression in transplanted cells when (111)In localization is available.

Methods: Canine bone marrow mesenchymal cells (BMMCs), radiolabelled and transfected, were injected into infarcted myocardium. Next, a reporter probe was injected systemically, and 22 SPECT scans were acquired over 20 h. Finally, (99m)Tc-sestamibi was injected and imaged. The animal was killed, the heart sectioned, and counted for (131)I and (111)In in a well-counter ('gold standard'). Canine SPECTs were reconstructed in two ways: with corrections for physical effects and without corrections. The first (111)In reconstruction and the (99m)Tc reconstruction were used to define volumes-of-interest over the transplanted BMMC (VBMMC) and normal myocardium (VNM), respectively.

Results: (131)I reconstructions without corrections for physical effects had negligible differential uptake. With corrections, VBMMC was consistently higher than VNM, demonstrating transgene expression. (131)I had the following VBMMC:VNM activity ratio: without correction for physical effects=0.869; with corrections=1.23; and well-counter=1.21. VNM showed the following (131)I:(111)In activity ratio: without corrections=3.07; with corrections=1.38; and well-counter=1.58.

Conclusions: In dual-isotope SPECT, corrections for physical effects were required to detect transgene expression in cells transplanted into an infarction when localization information was available.