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山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (10): 34-39.doi: 10.6040/j.issn.1671-7554.0.2015.1092

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125I-rFlic及125I-rFlicΔ180-400的制备及其在同种移植排斥监测中的作用

薛莹,张超,梁婷,宋静,侯桂华   

  1. 山东大学医学院实验核医学研究所, 山东 济南 250012
  • 收稿日期:2015-11-09 出版日期:2016-10-10 发布日期:2016-10-10
  • 通讯作者: 侯桂华. E-mail:ghhou1@hotmail.com E-mail:ghhou1@hotmail.com
  • 基金资助:
    国家自然科学基金(81371601)

Preparation and evaluation of 125I-rFlic and 125I-rFlicΔ180-400 in noninvasive radioimaging of allorejection

XUE Ying, ZHANG Chao, LIANG Ting, SONG Jing, HOU Guihua   

  1. Institute of Experimental Nuclear Medicine, Medical School of Shandong University, Jinan 250012, Shandong, China
  • Received:2015-11-09 Online:2016-10-10 Published:2016-10-10

摘要: 目的 探讨放射性碘125标记基因重组鞭毛蛋白(125I-rFlic)及其片段(125I-rFlicΔ180-400)在同种移植模型中的生物学分布及靶向性。 方法 用1,3,4,6-四氯-3α,6α-二苯基甘脲(Iodogen)碘化标记rFlic及rFlicΔ180-400,分析标记率及稳定性,进行放射性配基结合分析;构建小鼠同种/同系皮肤移植模型,于术后第8天尾静脉注射标记物,分析生物学分布和药代动力学特征,进行全身磷屏自显影显像。 结果 成功制备125I-rFlic及rFlicΔ180-400,且具有较好的体外稳定性;125I-rFlicΔ180-400对移植受体脾细胞亲和力更高。生物学分布结果显示,与125I-rFlic组相比,125I-rFlicΔ180-400注射组24 h的 移植皮片/对侧正常皮片(T/NT)明显升高,P=0.014 8。药代动力学结果表明,与125I-rFlic相比,125I-rFlicΔ180-400代谢更快。全身磷屏自显影显像显示,注射后6 h的同种移植皮片放射性浓聚较1 h更明显;与125I-rFlic组相比,125I-rFlicΔ180-400组移植皮片显像更加清晰。注射后24 h两组均可得到清晰移植皮片显像。 结论 125I-rFlic与125I-rFlicΔ180-400在移植皮片处高度特异性浓聚,可成功显示同种移植急性排斥,而后者比前者拥有更快的代谢率和更快的特异性浓聚。

关键词: 鞭毛蛋白, Toll样受体5, 同种移植急性排斥, 放射性碘

Abstract: Objective To evaluate the effect of iodine-125 labeled intact flagellin(125I-rFlic)and its fragment(125I-rFlicΔ180-400)in allograft acute rejection model on non-invasive monitoring allorejection. Methods The rFlic and rFlicΔ180-400 were labeled with iodine-125 with iodogen method, and label rate, stability and receptor binding activities were analyzed. After the allograft/isograft mice models were established, biodistribution, pharmacokinetics and phosphor-autoradiography imaging were detected on day 8 post transplantation after two tracers’ injection through tail vein separately. Results The prepared 125I-rFlic and 125I-rFlicΔ180-400 were stable. Radioligand-based binding assay showed 125I-rFlicΔ180-40 had higher affinity than 125I-rFlic. In ex vivo biodistribution study, 125I-rFlicΔ180-400 showed higher skin graft/opposite-side skin(T/NT)than 125I-rFlic 24 h after tracer injection(P=0.014 8). The pharmacokinetic results indicated the metabolism of125I-rFlicΔ180-400 was faster than that of 125I-rFlic. The whole-body autoradiography showed higher radioactivities in allograft 6 h than 1h after tracers’ injection, and allograft-radioimage of 125I-rFlicΔ180-400 6 h was much clearer than that of 125I-rFlic. Moreover, 125I-rFlic and 125I-rFlicΔ180-400 both showed preferentially graft-accumulated in the allorejection group after 24 h. Conclusion Both 125I-rFlic and 125I-rFlicΔ180-400 can specifically accumulate on graft in allorejection models; the latter is faster metabolized and earlier focused on allograft than the former.

Key words: Radioiodine, Toll-like receptor 5, Flagellin, Allotransplant acute rejection

中图分类号: 

  • R817-33
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[1] 赵姗姗,李晓梅,梁婷,张超,宋静,侯桂华. 自噬对125I-anti-TLR5同种移植排斥靶向显像的影响[J]. 山东大学学报(医学版), 2017, 55(9): 46-52.
[2] 杨欢,梁婷, 张超, 宋静,郝静,侯桂华 . 131I- rFliC的制备及乳腺癌荷瘤鼠体内生物学分布特征[J]. 山东大学学报(医学版), 2012, 50(12): 31-36.
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