Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Building 75, 149 13th St, Charlestown, MA 02129, USA.
Radiology. 2013 Mar;266(3):822-30. doi: 10.1148/radiol.12121129. Epub 2012 Dec 21.
To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a long-circulating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium-diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption.
All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 × 10(6) splenocytes from 6-week-old nonobese diabetic mice. These mice also served as control subjects for comparison of pre- and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance.
MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec ± 39.3 and 239.5 msec ± 17.6, respectively; P < .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium.
PGC-Gd-DTPA-F-enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge.
通过使用一种长循环顺磁 T1 对比剂，即与荧光素异硫氰酸酯（Gd-DTPA-F）共价连接的保护性接枝共聚物（PGC），来检测胰岛细胞移植小鼠模型中的过继免疫攻击。该共聚物在以血管破坏为特征的炎症部位积聚。
所有动物实验均符合机构准则，并获得研究动物护理小组的批准。6 只非肥胖型糖尿病严重联合免疫缺陷小鼠接受了胰岛细胞移植，并接受了来自 6 周龄非肥胖型糖尿病小鼠的 5×10(6)个脾细胞过继转移。这些小鼠也作为对照，用于比较过继转移前后的磁共振成像结果。仅接受磷酸盐缓冲盐水溶液的小鼠作为非过继转移对照（n=2）。在静脉注射 PGC-Gd-DTPA-F 前后进行了体内磁共振（MR）成像，并进行了组织学检查。通过配对学生 t 检验和重复双向方差分析来分析统计差异。
MR 成像结果显示，与过继转移前相比，在由脾细胞过继转移引发的免疫攻击后，PGC-Gd-DTPA-F 在移植物区域的积聚明显增加（T1 值分别为 137.2 毫秒±39.3 和 239.5 毫秒±17.6；P<.001）。这些结果在组织学检查中得到了证实，结果显示造影剂大量渗漏到胰岛细胞间质中。
PGC-Gd-DTPA-F 增强磁共振成像允许对移植 T 细胞挑战的血管损伤进行体内评估。
