Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F
Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F
复制标题
使用肽探针 Tc-99m-HYNIC-H10F 对曲妥珠单抗治疗期间乳腺癌中的 HER2 表达进行成像和监测
DOI：
10.1007/s00259-020-04754-6
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发表时间：
2020-03-13
影响因子：
9.1
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Wu, Yue;Li, Liqiang;Wang, Fan
目的研制新型分子成像探针（99m） tc - hynici - h10f，通过SPECT成像检测乳腺癌HER2表达，对曲妥珠单抗进行患者筛查和疗效监测。方法采用（99m）Tc标记H10F肽，按照优化方案制备Tc-99m- hynic -H10F。分别对her2阳性的SK-BR3和her2阴性的MDA-MB-231人乳腺癌异种移植物小鼠模型进行生物分布和SPECT/CT。在两种her2阳性乳腺癌模型（SK-BR3和MDA-MB-361）中，通过SPECT/CT监测和量化曲妥珠单抗的治疗反应。初步临床研究是在两名乳腺癌患者中进行的。结果（99m）Tc-HYNIC-H10F的SPECT/CT显示SK-BR3肿瘤清晰可见，而MDA-MB-231肿瘤信号较低。过量的未标记的H10F肽可以阻断肿瘤对（99m）Tc-HYNIC-H10F的摄取，但过量的曲妥珠单抗不能。治疗后第11天，两个her2阳性肿瘤的生长明显受到抑制。然而，SPECT/CT在治疗后第4天反映出更早的治疗反应。采用（99m）Tc-HYNIC-H10F SPECT/CT显像检测乳腺癌患者肿瘤中HER2的表达。结论Tc-99m-HYNIC-H10F在her2阳性肿瘤中特异性积累。与曲妥珠单抗相比，tc -99m- hyic - h10f与HER2抗原的不同结构域结合，为曲妥珠单抗治疗前/期间/后监测HER2表达水平提供了新的机会，从而实现更有效的个性化治疗。
Purpose The novel molecular imaging probe(99m)Tc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer. Methods Tc-99m-HYNIC-H10F was developed by labeling H10F peptide with(99m)Tc following an optimized protocol. Biodistribution and SPECT/CT were performed in mouse models bearing HER2-positive SK-BR3 and HER2-negative MDA-MB-231 human breast cancer xenografts, respectively. The treatment response to trastuzumab was monitored and quantified by SPECT/CT in two HER2-positive breast cancer models (SK-BR3 and MDA-MB-361). The preliminary clinical study was performed in two patients with breast cancer. Results SPECT/CT with(99m)Tc-HYNIC-H10F showed that the SK-BR3 tumors were clearly visualized, while the signals from MDA-MB-231 tumors were much lower. The tumor uptake of(99m)Tc-HYNIC-H10F could be blocked by excess unlabeled H10F peptide but not by excess trastuzumab. The growth of two HER2-positive tumors was prominently suppressed at day 11 post-treatment. However, SPECT/CT reflected much earlier therapy response at day 4 post-treatment. The HER2 expression in tumors of breast cancer patients could be detected by(99m)Tc-HYNIC-H10F SPECT/CT imaging. Conclusions Tc-99m-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab,Tc-99m-HYNIC-H10F binds to a different domain of HER2 antigen, providing new opportunities to monitor HER2 expression levels before/during/after trastuzumab treatment for more effective personalized treatment.