AUTHOR=Wen Li , Xia Lei , Guo Xiaoyi , Huang Hai-Feng , Wang Feng , Yang Xian-teng , Yang Zhi , Zhu Hua 

TITLE=Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.778728

DOI=10.3389/fonc.2021.778728

ISSN=2234-943X

ABSTRACT=Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer, it still remains problems with cardiotoxicity, drug resistance and unpredictable efficacy. Herein, we construced novel  organic dopmelanin nanoparticles (dMNs) as a carrier and surface-loaded with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenografts (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specificity targeting the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, the micro-PET/CT and PET/MRI maging showed the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs a carrier (1.63 ± 0.07 vs 0.90 ± 0.04 at 24 h, P = 0.002), similarity found in 64Cu-labled Her-PEG-dMNPs. Due to 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the 124I-Her-PEG-dMNPs further evaluations. Furthermore, the immunohistochemistry staining confirmed the overexpression of HER2 in animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.