^(99m)Tc-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

A dual-modality SPECT/MR probe of ^(99m)Tc-Transferrin-DTPA-Gd for the detection of tumor transferrin receptor expression in vivo

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^(99m)Tc-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^(99m)Tc-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^(99m)Tc-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:^(99m)Tc-Tf-DTPA-Gd可在体、无创性反映肿瘤表达TfR受体情况。

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 MDA-MB-468 was enhanced distinctly,while the signal of PC-3 tumor approximated the pre-injection.The rSE between MDA-MB-468and 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.