Development and Evaluation of a Novel Radiotracer 125I-rIL-27 to Monitor Allotransplant Rejection by Specifically Targeting IL-27Rα

IF 2.8 4区 医学 Q2 Medicine Molecular Imaging Pub Date : 2023-02-23 DOI:10.1155/2023/4200142
Shanshan Zhao, Qian Liu, F. Gao, G. Hou
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Abstract

Noninvasive monitoring of allograft rejection is beneficial for the prognosis of patients with organ transplantation. Recently, IL-27/IL-27Rα was proved in close relation with inflammatory diseases, and 125I-anti-IL-27Rα mAb our group developed demonstrated high accumulation in the rejection of the allograft. However, antibody imaging has limitations in the imaging background due to its large molecular weight. Therefore, we developed a novel radiotracer (iodine-125-labeled recombinant IL-27) to evaluate the advantage in the targeting and imaging of allograft rejection. In vitro specific binding of 125I-rIL-27 was determined by saturation and competitive assay. Blood clearance, biodistribution, phosphor autoradioimaging, and IL-27Rα expression were studied on day 10 after transplantation (top period of allorejection). Our results indicated that 125I-rIL-27 could bind with IL-27Rα specifically and selectively in vitro. The blood clearance assay demonstrated fast blood clearance with 13.20 μl/h of 125I-rIL-27 staying in the blood after 24 h. The whole-body phosphor autoradiography and biodistribution assay indicated a higher specific uptake of 125I-rIL-27 and a clear radioimage in allograft than in syngraft at 24 h, while a similar result was obtained at 48 h in the group of 125I-anti-IL-27Rα mAb injection. Meanwhile, a higher expression of IL-27Rα was found in the allograft by Western blot. The accumulation of radioactivity of 125I-rIL-27 was highly correlated with the expression of IL-27Rα in the allograft. In conclusion, 125I-rIL-27 could be a promising probe for acutely monitoring allograft rejection with high specific binding towards IL-27Rα on allograft and low imaging background.
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特异性靶向IL-27Rα监测同种异体移植排斥反应的新型放射性示踪剂125I-rIL-27的研制与评价
无创监测同种异体移植物排斥反应有利于器官移植患者的预后。最近,IL-27/IL-27Rα被证明与炎症性疾病密切相关,我们小组开发的125I-抗IL-27R抗体在同种异体移植物排斥反应中表现出高积累。然而,抗体成像由于其大分子量而在成像背景中具有局限性。因此,我们开发了一种新的放射性示踪剂(碘-125标记的重组IL-27)来评估其在同种异体移植物排斥反应靶向和成像方面的优势。125I-rIL-27的体外特异性结合通过饱和和竞争测定来确定。在移植后第10天(同种异体排斥反应的高峰期)研究血液清除率、生物分布、荧光放射自显影和IL-27Rα的表达。结果表明,125I-rIL-27在体外可与IL-27Rα特异性、选择性结合。血液清除率测定显示血液清除率很快,为13.20 μl/h的125I-rIL-27在24小时后留在血液中 h.全身荧光放射自显影和生物分布测定表明,在24小时时,同种异体移植物对125I-rIL-27的特异性摄取和清晰的放射性图像高于同异体移植物 h、 而在48 注射125I-抗IL-27RαmAb组h。同时,Western blot发现IL-27Rα在同种异体移植物中有较高的表达。125I-rIL-27的放射性积累与IL-27Rα的表达高度相关。总之,125I-rIL-27是一种很有前途的急性监测同种异体移植排斥反应的探针,具有对IL-27Rα的高特异性结合和低成像背景。
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来源期刊
Molecular Imaging
Molecular Imaging 生物-核医学
CiteScore
4.50
自引率
3.60%
发文量
21
审稿时长
>12 weeks
期刊介绍: Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.
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