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

Abstract

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. 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. (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. 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.