Reifschneider Olga, Wentker Kristina S, Strobel Klaus, Schmidt Rebecca, Masthoff Max, Sperling Michael, Faber Cornelius, Karst Uwe
†Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstr. 30, 48149 Münster, Germany.
‡Westfälische-Wilhelms-Universität Münster, University Hospital, Department of Clinical Radiology, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Anal Chem. 2015 Apr 21;87(8):4225-30. doi: 10.1021/ac504363q. Epub 2015 Apr 2.
Due to the fact that cellular therapies are increasingly finding application in clinical trials and promise success by treatment of fatal diseases, monitoring strategies to investigate the delivery of the therapeutic cells to the target organs are getting more and more into the focus of modern in vivo imaging methods. In order to monitor the distribution of the respective cells, they can be labeled with lanthanide complexes such as thulium-1,4,7,10-tetraazacyclodoecane-α,α,α,α-tetramethyl-1,4,7,10-tetraacetic acid (Tm(DOTMA)). In this study, experiments on a mouse model with two different cell types, namely, tumor cells and macrophages labeled with Tm(DOTMA), were performed. The systemic distribution of Tm(DOTMA) of both cell types was investigated by means of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS). Using the high resolution of 25 μm, distribution maps of Tm in different tissues such as tumor, liver, lung, and spleen as well as in explanted gel pellets were generated and the behavior of the labeled cells inside the tissue was investigated. Additionally, quantitative data were obtained using homemade matrix-matched standards based on egg yolk. Using this approach, limits of detection and quantification of 2.2 and 7.4 ng·g(-1), respectively, and an excellent linearity over the concentration range from 0.01 to 46 μg·g(-1) was achieved. The highest concentration of the label agent, 32.4 μg·g(-1), in tumor tissue was observed in the area of the injection of the labeled tumor cells. Regarding the second experiment with macrophages for cell tracking, Tm was detected in the explanted biogell pellet with relatively low concentrations below 60 ng·g(-1) and in the liver with a relatively high concentration of 10 μg·g(-1). Besides thulium, aluminum was detected with equal distribution behavior in the tumor section due to a contamination resulting from the labeling procedure, which includes the usage of an Al electrode.
由于细胞疗法在临床试验中的应用越来越广泛，并有望通过治疗致命疾病取得成功，因此研究治疗性细胞向靶器官递送的监测策略越来越成为现代体内成像方法的焦点。为了监测相应细胞的分布，可以用镧系元素配合物如铥-1,4,7,10-四氮杂环十二烷-α,α,α,α-四甲基-1,4,7,10-四乙酸（Tm(DOTMA)）对细胞进行标记。在本研究中，对用Tm(DOTMA)标记的两种不同细胞类型（即肿瘤细胞和巨噬细胞）的小鼠模型进行了实验。通过激光烧蚀-电感耦合等离子体质谱法（LA-ICPMS）研究了两种细胞类型的Tm(DOTMA)的全身分布。利用25μm的高分辨率，生成了不同组织（如肿瘤、肝脏、肺和脾脏）以及外植凝胶颗粒中Tm的分布图，并研究了标记细胞在组织内的行为。此外，使用基于蛋黄的自制基质匹配标准获得了定量数据。采用这种方法，检测限和定量限分别为2.2和7.4 ng·g(-1)，在0.01至46μg·g(-1)的浓度范围内具有出色的线性。在标记肿瘤细胞注射区域观察到肿瘤组织中标记剂的最高浓度为32.4μg·g(-1)。关于用于细胞追踪的巨噬细胞的第二个实验，在外植生物凝胶颗粒中检测到Tm，浓度相对较低，低于60 ng·g(-1)，在肝脏中检测到的浓度相对较高，为10μg·g(-1)。除了铥，由于标记过程中的污染（包括使用铝电极），在肿瘤切片中检测到铝具有相同的分布行为。
