Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model
Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model
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DOI：
10.1148/radiol.14132172
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发表时间：
2015-01-01
期刊：
影响因子：
19.7
通讯作者：
Larson, Andrew C.
中科院分区：
文献类型：
--
作者：
Zhang, Zhuoli;Li, Weiguo;Larson, Andrew C.
目的：为了在胰腺癌的鼠模型中测试以下假设：（a）用负载抗原的铁标记的树突状细胞接种疫苗降低外周引流淋巴结（LN）内磁共振（MR）成像时的T2加权信号强度，和（B）这种信号强度降低与树突状细胞接种疫苗后的肿瘤大小变化相关。机构动物护理和使用委员会批准了本研究。将Panc 02细胞双侧植入27只C57 BL/6小鼠的侧腹。在肿瘤达到10 mm后，评价细胞活力，并将铁标记的树突状细胞疫苗注射到左后足垫中。将小鼠随机分为以下三组（每组n = 9）：第1组注射100万个铁标记的树突状细胞;第2组注射200万个细胞;对照组注射200 mL磷酸盐缓冲盐水。在细胞注射前和注射后6小时和24小时进行标记的树突状细胞迁移到引流LN的T1和T2加权MR成像。测量引流LN的信噪比（SNR）。使用单因素方差分析（ANOVA）比较LN中普鲁士蓝阳性树突状细胞测量值。结果：台盼蓝分析显示，平均存活指数无显著差异（未标记与标记树突状细胞，4.32% +/- 0.69 [标准差] vs 4.83% +/- 0.76; P = 0.385）。注射后35天，100万个树突状细胞组的平均左侧和右侧肿瘤大小分别为112.7 mm（2）+/- 16.4和109 mm（2）+/- 24.3，200万个树突状细胞组为92.2 mm（2）+/- 9.9和90.4 mm（2）+/- 12.8，对照组为193.7 mm（2）+/- 20.9和189.4 mm（2）+/- 17.8（对照组与100万细胞组P = 0.0001;对照组与200万细胞组P = 0.00007）。注射后T2加权SNR下降在左侧腘淋巴结注射后24小时和大小的变化，在后续的肿瘤两侧（R = 0.81和R = 0.76左右肿瘤，分别）之间存在相关性：MR成像方法可用于定量测量积累的铁标记的树突状细胞为基础的疫苗引流淋巴结。引流LN中基于树突状细胞的疫苗的量与观察到的保护作用密切相关。(C)RSNA，2014年
Purpose: To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes (LNs) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination.Materials and Methods: The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LNs was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio (SNR) of the draining LNs was measured. One-way analysis of variance (ANOVA) was used to compare Prussian blue-positive dendritic cell measurements in LNs. Repeated-measures ANOVA was used to compare in vivo T2-weighted SNR LN measurements between groups over the observation time points.Results: Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% +/- 0.69 [ standard deviation] vs 4.83% +/- 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm(2) +/- 16.4 and 109 mm(2) +/- 24.3 for the 1-million dendritic cell group, 92.2 mm(2) +/- 9.9 and 90.4 mm(2) +/- 12.8 for the 2-million dendritic cell group, and 193.7 mm(2) +/- 20.9 and 189.4 mm(2) +/- 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR decreases in the left popliteal LN 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively).Conclusion: MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell-based vaccines in draining LNs. The amount of dendritic cell-based vaccine in draining LNs correlates well with observed protective effects. (C) RSNA, 2014