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

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。

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

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.