HER2分子影像探针99mTc-HP7的放射性标记与肿瘤SPECT/CT显像  

Radiolabeling and cancer SPECT/CT imaging of HER2-targeted molecular imaging probe 99mTc-HP7

作　　者：宋宏杰 张健 石琴[1,2] 周治国 王明伟 无 SONG Hongjie;ZHANG Jian;SHI Qin;ZHOU Zhiguo;WANG Mingwei;无(Department of Nuclear Medicine,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Center for Biomedical Imaging,Fudan University,Shanghai 200032,China;Shanghai Engineering Research Center of Molecular Imaging Probes,Shanghai 200032,China;College of Chemistry and Materials Sciences,Shanghai Normal University,Shanghai 200234,China)

机构地区：[1]复旦大学附属肿瘤医院核医学科,复旦大学上海医学院肿瘤学系,上海200032 [2]复旦大学生物医学影像研究中心,上海200032 [3]上海分子影像探针工程技术研究中心,上海200032 [4]上海师范大学化学与材料科学学院,上海200234

出　　处：《肿瘤影像学》2020年第2期161-168,共8页Oncoradiology

基　　金：国家自然科学基金(21771041)。

摘　　要：目的:开发人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)靶向性分子影像探针99mTcHP7的放射性标记制备方法,并开展其在不同HER2表达水平的肿瘤模型单光子发射型计算机断层显像/计算机断层扫描(single-photon emission computed tomography/computed tomography,SPECT/CT)显像研究。方法:在共配体三(羟甲基)甲基甘氨酸(Tricine)和乙二胺二乙酸(EDDA)存在的磷酸盐溶液(pH=6.0)体系中,核素99mTc与前体多肽HYNICLTVSPWY(HP7)在100℃加热条件下发生标记反应,制备探针99mTc-HP7。利用放射性薄层色谱(radioactive thin layer chromatography,Radio-TLC)分析其标记率、放射化学纯度,以及在0.9%NaCl溶液和血清中的体外稳定性。建立3种HER2表达水平不同的人胃癌NCI-N87、卵巢癌SKOV-3、结肠癌HT-29细胞的BALB/c裸小鼠移植瘤模型,于注射后0.5、1.0和3.0h进行SPECT/CT显像,计算肿瘤摄取%ID/g值和肿瘤(T)-肌肉(M)摄取比(T/M)。获取肿瘤组织,进行HER2表达的蛋白质印迹法(Western blot)和免疫组织化学(immunohistochemistry,IHC)实验。利用SPSS 20.0软件,分析体内99mTc-HP7肿瘤摄取与离体肿瘤组织HER2表达水平的相关性。结果:99mTc-HP7标记率和放射化学纯度大于95%,体外稳定性良好。99mTc-HP7在HER2阳性肿瘤中的SPECT/CT显像清楚,注射后1.0 h时肿瘤摄取%ID/g值最大,而3.0 h时T/M值最高。NCI-N87、SKOV-3和HT-29这3种肿瘤在各时间点摄取99mTc-HP7的%ID/g和T/M依次降低,同时Western blot和IHC测量结果证实三种肿瘤组织的HER2表达水平为高、中、低的趋势。相关性分析表明,99mTc-HP7肿瘤摄取与HER2表达具有明显的正相关关系(P<0.01)。结论:99mTc-HP7的标记率高,制备方法简便,其SPECT/CT显像能够区分HER2表达水平不同的肿瘤类型,具有作为HER2分子影像探针的良好性质和潜力。Objective:To develop the radiolabeling preparation of human epidermal growth factor receptor 2(HER2)targeted molecular imaging probe 99mTc-HP7 and to investigate its single-photon emission computed tomography/computed tomography(SPECT/CT)imaging of tumor models with different HER2 expression levels in this study.Methods:99mTc-HP7 was prepared by the radiolabeling reaction of nuclide 99mTc and the precursor peptide HYNIC-LTVSPWY(HP7)at 100℃in the phosphate solution(pH-6.0)with the presence of co-ligands Tricine and EDDA.Radioactive thin layer chromatography(Radio-TLC)was used to analyze the radiolabeling efficiency,radiochemical purity and in vitro stability in saline and serum.SPECT/CT imaging of three tumor-bearing mouse models(NCI-N87,SKOV-3,HT-29)with different HER2 expression levels were acquired at 0.5,1.0 and 3.0 h post injection(p.i),and the tumor uptake value%ID/g and tumor-muscle uptake ratio(T/M)were quantitatively calculated.HER2 expression in the tumor tissues was measured by Western blot and immunohistochemical(IHC)tests.The correlation between 99mTc-HP7 uptake and HER2 expression in vivo was analyzed by SPSS 20.0 software.Results:The radiolabeling efficiency and radiochemical purity of 99mTc-HP7 were more than 95%,with great stability in vitro.99mTc-HP7 SPECT/CT imaging clearly visualized HER2-positive tumors with the highest uptake%ID/g at 1.0 h p.i and the highest T/M at 3.0 h p.i.%ID/g and T/M of 99mTc-HP7 uptake in NCI-N87,SKOV-3 and HT-29 tumors decreased in turn at each time point.Meanwhile,Western blot and IHC confirmed that HER2 expression level in the three kinds of tumor tissues was high,medium and low.Correlation analysis showed that there was a significant positive correlation between 99mTc-HP7 tumor uptake and HER2 expression(P<0.001).Conclusion:99mTc-HP7 was obtained using a facile preparation method with high radiolabeling efficiency,and its SPECT/CT imaging could distinguish the tumor types with different HER2 expression levels,which indicated 99mTc-HP7 has favorable properties and

关 键 词：核素99mTc 放射性标记 分子影像探针 多肽 单光子发射型计算机断层显像/计算机断层扫描显像 人表皮生长因子受体2 肿瘤 

分 类 号：R445.5[医药卫生—影像医学与核医学]