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 In-111-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 I-131-labelled reporter probe. The method is impeded by the physical effects of scatter, I-131/In-111 cross-talk, and attenuation. We hypothesize that correcting for physical effects improves detection of transgenic expression in transplanted cells when In-111 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, Tc-99m-sestamibi was injected and imaged. The animal was killed, the heart sectioned, and counted for I-131 and In-111 in a well-counter ('gold standard'). Canine SPECTs were reconstructed in two ways: with corrections for physical effects and without corrections. The first In-111 reconstruction and the Tc-99m reconstruction were used to define volumes-of-interest over the transplanted BMMC (VBMMC) and normal myocardium (VNM), respectively. Results I-131 reconstructions without corrections for physical effects had negligible differential uptake. With corrections, VBMMC was consistently higher than VNM, demonstrating transgene expression. 131 1 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 I-131:In-111 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.