Sun Hukui, Yang Guangjie, Liang Ting, Zhang Chao, Song Jing, Han Jiankui, Hou Guihua
Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Experimental Nuclear Medicine, School of Medicine, Shandong University, Ji'nan, Shandong, China.
J Cell Mol Med. 2014 Dec;18(12):2437-44. doi: 10.1111/jcmm.12423. Epub 2014 Oct 6.
Although (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can be used for the non-invasive detection and monitoring of allograft rejection by activated leucocytes, this non-specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a (131)I-radiolabelled anti-Toll-like receptor 5 (TLR5) mAb for non-invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non-specific radiotracer (18)F-FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB/c mice transplanted with C57BL/6 skin grafts, with or without rapamycin treatment (named as allo-treated group or allo-rejection group), were injected with (131)I-anti-TLR5 mAb, (18)F-FDG, or mouse isotype (131)I-IgG, respectively. Whole-body phosphor-autoradiography and ex vivo biodistribution studies were obtained. Whole-body phosphor-autoradiography showed (131)I-anti-TLR5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The (131)I-anti-TLR5 mAb had significantly higher graft uptake and target-to-non-target ratio in the allo-treated group, as determined by semi-quantification of phosphor-autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high (18)F-FDG uptake was not observed in the allo-treated group. The highest allograft-skin-to-native-skin ratio (A:N) of (131)I-anti-TLR5 mAb uptake was significantly higher than the ratio for (18)F-FDG (7.68 versus 1.16, respectively). (131)I-anti-TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of (131)I-IgG was comparable in both groups. We conclude that radiolabelled anti-TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin.
虽然（18）F - 氟脱氧葡萄糖（（18）F - FDG）摄取可用于通过活化白细胞对同种异体移植排斥反应进行无创检测和监测，但这种非特异性积聚很容易受到免疫抑制剂的影响。我们的目的是评估一种（131）I标记的抗Toll样受体5（TLR5）单克隆抗体，用于在同种异体移植小鼠模型中进行无创体内移植物可视化和定量分析，并与使用免疫抑制剂情况下的非特异性放射性示踪剂（18）F - FDG进行比较。进行了标记、结合和稳定性研究。将移植了C57BL / 6皮肤移植物的BALB / c小鼠，分为接受或未接受雷帕霉素治疗（分别命名为同种异体治疗组或同种异体排斥组），分别注射（131）I - 抗TLR5单克隆抗体、（18）F - FDG或小鼠同种型（131）I - IgG。进行了全身磷光放射自显影和离体生物分布研究。全身磷光放射自显影显示，（131）I - 抗TLR5单克隆抗体在1小时时摄取到血液灌注良好的器官中，并从12小时起显示出清晰的移植物图像。通过磷光放射自显影图像的半定量测定，（131）I - 抗TLR5单克隆抗体在同种异体治疗组中的移植物摄取和靶非靶比值显著更高；这些结果与离体生物分布研究一致。然而，在同种异体治疗组中未观察到高（18）F - FDG摄取。（131）I - 抗TLR5单克隆抗体摄取的最高同种异体皮肤与天然皮肤比值（A:N）显著高于（18）F - FDG的比值（分别为7.68和1.16）。移植物中（131）I - 抗TLR5单克隆抗体的摄取与同种异体移植区域中TLR5的表达显著相关。两组中（131）I - IgG的积聚相当。我们得出结论，放射性标记的抗TLR5单克隆抗体能够在用免疫抑制药物雷帕霉素治疗后以高靶特异性检测同种异体移植物。
