In Vivo SPECT Quantification of Transplanted Cell Survival After Engraftment Using 111In-Tropolone in Infarcted Canine Myocardium

Abstract

Current investigations of cell transplant therapies in damaged myocardium are limited by the inability to quantify cell transplant survival in vivo. We describe how the labeling of cells with (111)In can be used to monitor transplanted cell viability in a canine infarction model. We experimentally determined the contribution of the (111)In signal associated with transplanted cell (TC) death and radiolabel leakage to the measured SPECT signal when (111)In-labeled cells were transplanted into the myocardium. Three groups of experiments were performed in dogs. Radiolabel leakage was derived by labeling canine myocardium in situ with free (111)In-tropolone (n = 4). To understand the contribution of extracellular (111)In (e.g., after cell death), we developed a debris impulse response function (DIRF) by injecting lysed (111)In-labeled cells within reperfused (n = 3) and nonreperfused (n = 5) myocardial infarcts and within normal (n = 3) canine myocardium. To assess the application of the modeling derived from these experiments, (111)In-labeled cells were transplanted into infarcted myocardium (n = 4; 3.1 x 10(7) +/- 5.4 x 10(6) cells). Serial SPECT images were acquired after direct epicardial injection to determine the time-dependent radiolabel clearance. Clearance kinetics were used to correct for (111)In associated with viable TCs. (111)In clearance followed a biphasic response and was modeled as a biexponential with a short (T(1/2)(s)) and long (T(1/2)(l)) biologic half-life. The T(1/2)(s) was not significantly different between experimental groups, suggesting that initial losses were due to transplantation methodology, whereas the T(1/2)(l) reflected the clearance of retained (111)In. DIRF had an average T(1/2)(l) of 19.4 +/- 4.1 h, and the T(1/2)(l) calculated from free (111)In-tropolone injected in situ was 882.7 +/- 242.8 h. The measured T(1/2)(l) for TCs was 74.3 h and was 71.2 h when corrections were applied. A new quantitative method to assess TC survival in myocardium using SPECT and (111)In has been introduced. At the limits, method accuracy is improved if appropriate corrections are applied. In vivo (111)In imaging most accurately describes cell viability half-life if T(1/2)(l) is between 20 h and 37 d.