Imaging and monitoring HER2 expression in breast cancer during trastuzumab therapy with a peptide probe 99mTc-HYNIC-H10F
- 13 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in European Journal of Nuclear Medicine and Molecular Imaging
- Vol. 47 (11), 2613-2623
- https://doi.org/10.1007/s00259-020-04754-6
Abstract
Purpose The novel molecular imaging probe 99mTc-HYNIC-H10F was developed for patient screening and efficacy monitoring of trastuzumab therapy by SPECT imaging of HER2 expression in breast cancer. Methods 99mTc-HYNIC-H10F was developed by labeling H10F peptide with 99mTc 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 99mTc-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 99mTc-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 99mTc-HYNIC-H10F SPECT/CT imaging. Conclusions 99mTc-HYNIC-H10F specifically accumulates in HER2-positive tumors. Compared with trastuzumab, 99mTc-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.Keywords
Funding Information
- National Natural Science Foundation of China Project (81630045, 81571727, 81420108019, 81621063, 81427802)
- National Key R&D Program of China (2017YFA0205600)
- Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12020110)
- the Youth Innovation Promotion Association of Chinese Academy of Sciences (YIPACAS) project (2016090)
- Beijing Natural Science Foundation (BJNSF) project (7142086)
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