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

Journal of Nuclear Medicine

Benoit Lewden¹  Gerald Wisenberg¹  Jane Sykes¹  Robert Z. Stodilka¹  R. Glenn Wells¹  Frank S. Prato¹  Kimberley J. Blackwood¹ 

关键词: ¹¹¹In SPECT;    cell transplant survival;    myocardial infarction;    canine bone marrow stromal cells;    cell tracking;   

DOI  :  10.2967/jnumed.108.058966

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 111In can be used to monitor transplanted cell viability in a canine infarction model. Methods: We experimentally determined the contribution of the 111In signal associated with transplanted cell (TC) death and radiolabel leakage to the measured SPECT signal when 111In-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 111In-tropolone (n = 4). To understand the contribution of extracellular 111In (e.g., after cell death), we developed a debris impulse response function (DIRF) by injecting lysed 111In-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, 111In-labeled cells were transplanted into infarcted myocardium (n = 4; 3.1 × 107 ± 5.4 × 106 cells). Serial SPECT images were acquired after direct epicardial injection to determine the time-dependent radiolabel clearance. Clearance kinetics were used to correct for 111In associated with viable TCs. Results: 111In clearance followed a biphasic response and was modeled as a biexponential with a short () and long () biologic half-life. Thewas not significantly different between experimental groups, suggesting that initial losses were due to transplantation methodology, whereas thereflected the clearance of retained 111In. DIRF had an averageof 19.4 ± 4.1 h, and thecalculated from free 111In-tropolone injected in situ was 882.7 ± 242.8 h. The measuredfor TCs was 74.3 h and was 71.2 h when corrections were applied. Conclusion: A new quantitative method to assess TC survival in myocardium using SPECT and 111In has been introduced. At the limits, method accuracy is improved if appropriate corrections are applied. In vivo 111In imaging most accurately describes cell viability half-life ifis between 20 h and 37 d.

【 授权许可】

Unknown