Wu Yue, Li Liqiang, Wang Zihua, Shi Jiyun, Hu Zhiyuan, Gao Shi, Miao Weibing, Ma Qingjie, Dong Chengyan, Wang Fan
Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China, Beijing, 100190, China.
Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2613-2623. doi: 10.1007/s00259-020-04754-6. Epub 2020 Mar 13.
The novel molecular imaging probe Tc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer.
Tc-HYNIC-H10F was developed by labeling H10F peptide with 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.
SPECT/CT with 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 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 Tc-HYNIC-H10F SPECT/CT imaging.
Tc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, Tc-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.
开发新型分子成像探针Tc-HYNIC-H10F，用于通过SPECT成像检测乳腺癌中HER2表达，以进行患者筛选和曲妥珠单抗治疗疗效监测。
按照优化方案用Tc标记H10F肽，制备Tc-HYNIC-H10F。分别在荷HER2阳性SK-BR3和HER2阴性MDA-MB-231人乳腺癌异种移植瘤的小鼠模型中进行生物分布和SPECT/CT研究。在两种HER2阳性乳腺癌模型（SK-BR3和MDA-MB-361）中，通过SPECT/CT监测和定量曲妥珠单抗的治疗反应。对两名乳腺癌患者进行了初步临床研究。
Tc-HYNIC-H10F的SPECT/CT显示，SK-BR3肿瘤清晰可见，而MDA-MB-231肿瘤的信号低得多。过量未标记的H10F肽可阻断Tc-HYNIC-H10F的肿瘤摄取，但过量曲妥珠单抗则不能。治疗后第11天，两种HER2阳性肿瘤的生长受到显著抑制。然而，SPECT/CT在治疗后第4天就反映出更早的治疗反应。通过Tc-HYNIC-H10F SPECT/CT成像可检测乳腺癌患者肿瘤中的HER2表达。
Tc-HYNIC-H10F特异性聚集在HER2阳性肿瘤中。与曲妥珠单抗相比，Tc-HYNIC-H10F与HER2抗原的不同结构域结合，为在曲妥珠单抗治疗前/中/后监测HER2表达水平以实现更有效的个性化治疗提供了新机会。
