中国癌症杂志 ›› 2019, Vol. 29 ›› Issue (2): 119-124.doi: 10.19401/j.cnki.1007-3639.2019.02.004

• 论著 • 上一篇    下一篇

99mTc-转铁蛋白-DTPA-Gd核素/磁性双模态分子影像探针基于转铁蛋白受体表达水平的肿瘤成像

顾丙新1,2,3,孙玉云1,2,3,杨忠毅1,2,3,罗建民1,2,3,张建平1,2,3,章英剑1,2,3   

  1. 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
  • 出版日期:2019-02-28 发布日期:2019-03-25
  • 通信作者: 章英剑 E-mail: yjzhang111@aliyun.com
  • 基金资助:
    上海分子影像探针工程技术研究中心项目(14DZ2251400)。

A dual-modality SPECT/MR probe of 99mTc-Transferrin-DTPA-Gd for the detection of tumor transferrin receptor expression in vivo

GU Bingxin1,2,3, SUN Yuyun1,2,3, YANG Zhongyi1,2,3, LUO Jianmin1,2,3, ZHANG Jianping1,2,3, ZHANG Yingjian1,2,3   

  1. 1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; 3. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China
  • Published:2019-02-28 Online:2019-03-25
  • Contact: ZHANG Yingjian E-mail: yjzhang111@aliyun.com

摘要: 背景与目的:转铁蛋白(Holo-Transferrin,Tf)受体(transferrin receptor,TfR)广泛存在于恶性肿瘤细胞膜表面,并被认为是抗肿瘤治疗的靶点。本研究旨在探讨99mTc-Tf-DTPA-Gd在体、无创性检测多种人源性肿瘤TfR表达情况的可行性。方法:制作10种人肿瘤细胞的BALB/c裸小鼠移植瘤模型;经荷瘤鼠尾静脉注射99mTc-Tf-DTPA-Gd或Tf-DTPA-Gd 4 h后行单光子发射计算机断层摄影术(single-photon emission computed tomography,SPECT)/计算机断层摄影术(computed tomography,CT)或磁共振成像(magnetic resonance imaging,MRI)检查,勾画感兴趣区(region of interest,ROI),计算靶本比值即靶区/肌肉组织(target-to-muscle ratios,T/M)或相对信号增强值(relative signal enhancement,rSE);显像结束后取肿瘤组织行H-E染色及免疫组织化学染色,采用H-score法评估10种肿瘤表达TfR水平。选用两样本t检验及Spearman分析数据。结果:10种移植瘤模型均可用于成像。注射双模态探针4 h后,有9种肿瘤摄取99mTc-Tf-DTPA-Gd,其中胶质瘤细胞U87的T/M值最高,乳腺癌细胞MDA-MB-468也有较高的T/M值;而前列腺癌细胞PC-3肿瘤几乎不摄取,T/M值接近1,与MDA-MB-468 T/M值相比差异有统计学意义(t=6.919,P=0.002)。MRI显示,MDA-MB-468肿瘤强化明显,rSE达(154.88±8.71)%,而PC-3肿瘤为(111.31±3.46)%,差异有统计学意义(t=8.441,P=0.001)。PC-3肿瘤几乎不表达TfR,其余9种肿瘤均不同程度地表达TfR。TfR免疫组织化学检测结果与探针的T/M值呈明显的正相关(相关系数为r=0.915,P<0.001)。结论:99mTc-Tf-DTPA-Gd可在体、无创性反映肿瘤表达TfR受体情况。

关键词: 转铁蛋白受体, 分子影像, 双模态, 磁共振成像, 免疫组织化学

Abstract: Background and purpose: Transferrin (Tf) receptor (TfR) is expressed broadly in malignant cells, and has been developed as a target for anti-tumor therapy. This study aimed to investigate the feasibility of 99mTc-Tf-DTPA-Gd noninvasively detecting tumor TfR expression in vivo. Methods: We established 10 xenograft tumor models with mice. 99mTc-Tf-DTPA-Gd and Tf-DTPA-Gd were injected into mice via tail vein respectively, and 4 hours later single-photon emission computed tomography (SPECT)/ computed tomography (CT) and magnetic resonance imaging (MRI) were acquired. The values of target-to-muscle ratios (T/M) and relative signal enhancement (rSE) were calculated by drawing regions of interest (ROI) in tumors. H-E staining and immunohistochemistry detection were applied when imaging was completed. Statistical analysis was performed using two-sample t test. Results: The tumors were clearly visible except PC-3 after administration with 99mTc-Tf-DTPA-Gd. The value of T/M between MDA-MB-468 and PC-3 showed statistically significant difference (t=6.919, P=0.002). In MRI experiment, the tumor of MDAMB-468 was enhanced distinctly, while the signal of PC-3 tumor approximated the pre-injection. The rSE between MDA-MB-468 and PC-3 also showed statistically significant difference (t=8.441, P=0.001). Immunohistochemistry staining showed 9 of these xenograft tumor models expressing TfR in various degree rather than PC-3 tumor. Conclusion: 99mTc-Tf-DTPA-Gd could serve as an ideal probe for detecting tumor TfR expression in vivo noninvasively.

Key words: Transferrin receptor, Molecular imaging, Dual-modality, Magnetic resonance imaging, Immunohistochemistry