靶向FPR2新型探针^(99m)Tc-WRWWWW的制备及其在炎症小鼠模型的初步研究  

Preparation of a novel probe^(99m)Tc-WRWWWW targeting FPR2 and its preliminary study in inflammatory mouse model

作　　者：潘芯 肖晴 朱家序 徐葵 汤帅虎 徐卓硕 周晓琪 李崇佼 雷萍[2] 何勇 PAN Xin;XIAO Qing;ZHU Jiaxu;XU Kui;TANG Shuaihu;XU Zhuoshuo;ZHOU Xiaoqi;LI Chongjiao;LEI Ping;HE Yong(Dept.of Nuclear Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China;Dept.of Immunology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China)

机构地区：[1]武汉大学中南医院核医学科,湖北武汉430071 [2]华中科技大学同济医学院基础医学院免疫学系,湖北武汉430030

出　　处：《武汉大学学报（医学版）》2023年第6期682-687,共6页Medical Journal of Wuhan University

基　　金：国家自然科学基金面上项目资助(编号:82171986;81871391)。

摘　　要：目的:构建靶向甲酰肽受体2(FPR2)的新型分子探针^(99m)Tc-WRWWWW,并评估其在正常昆明小鼠体内的药代动力学特点及在炎症模型鼠中的靶向效能。方法:核素^(99m)Tc标记WRWWWW,高效液相色谱法(HPLC)测定标记产物的放射化学纯度及体外稳定性。生物分布实验(30、60、120、240 min时间点)研究探针在正常昆明鼠体内药代动力学特点。构建急性肌肉炎症及结肠炎模型鼠,并进行小动物SPECT/CT显像。HE染色与免疫组化验证炎症组织免疫细胞浸润及FPR2表达水平。结果:成功构建新型探针^(99m)Tc-WRWWWW,标记率大于90%,放化纯大于99%,体外稳定性良好。正常昆明小鼠生物分布显示^(99m)Tc-WRWWWW主要经肝、肾代谢,60 min时肝、肾摄取值分别为(15.33±0.76)和(4.50±1.50)%ID/g。小动物SPECT/CT显像示实验组小鼠肌肉及结肠炎症病灶处放射性摄取较对照组小鼠明显增高,并能被过量非标记肽所阻断,探针具有较好的灵敏度和特异性。HE染色及免疫组化证实炎症肌肉内见大量免疫细胞浸润,FPR2表达水平升高,进一步验证了体内显像结果。结论:本研究成功制备靶向FPR2新型多肽分子探针^(99m)Tc-WRWWWW,标记率高且稳定性好,该探针可特异靶向炎症显像,对于炎症的无创监测具有一定的应用价值。Objective:To construct a novel molecular probe^(99m)Tc-WRWWWW targeting the formyl peptide receptor 2(FPR2)and to study its pharmacokinetics in normal Kunming(KM)mice and evaluate its imaging effect in inflammation-bearing mice.Methods:The ligand peptide was labeled by nuclide^(99m)Tc,and the quality control and stability of^(99m)Tc-WRWWWW in vitro were determined by high performance liquid chromatography(HPLC).Biodistribution were performed in healthy KM mice(time points:30,60,120,240 min)to study pharmacokinetics of the probe in vivo.Acute muscle inflam-mation and colitis mice models were established and used for micro SPECT/CT imaging.HE and immunohistochemical stain were performed to analyze the infiltration of immune cells and FPR2 expression.Results:^(99m)Tc-WRWWWW was successfully labeled with an overall radiochemical yield over 90%,radiochemical purity over 99%and excellent stability in vitro.Biodistribution of normal KM mice showed the probe was mainly excreted through liver and kidney(the uptake in 60 min was[15.33±0.76]and[4.50±1.50]%ID/g,respectively).Micro SPECT/CT imaging showed the in-flamed muscle and colitis lesions of experiment group had obviously higher radioactivity uptake as compared with control group,and the radioactive uptake could be blocked by excessive unlabeled pep-tide,suggesting the superior sensitivity and specificity of^(99m)Tc-WRWWWW.HE staining showed that inflammatory muscle tissue was infiltrated by many inflammatory cells and the expression of FPR2 was increased,further verifying the imaging results in vivo.Conclusion:In this research,a novel peptide probe^(99m)Tc-WRWWWW targeting FPR2 was successfully synthesized.^(99m)Tc-WRWW-WW shares the advantages of high radiochemical yield,excellent stability and high radioactivity uptake in the inflammation-bearing mice,which has important diagnostic value for non-invasive monitoring inflammation.

关 键 词：甲酰肽受体 ^(99m)Tc SPECT 炎症显像 

分 类 号：R817.[医药卫生—影像医学与核医学]