Polyethylene glycol-conjugated HER2-targeted peptides as a nuclear imaging probe for HER2-overexpressed gastric cancer detection in vivo
Journal
Journal of Translational Medicine
Journal Volume
16
Journal Issue
1
Date Issued
2018
Author(s)
Abstract
Background: The human epidermal growth factor receptor 2 (HER2) involved proliferation, angiogenesis, and reduced apoptosis in gastric cancer (GC), which is a common target for tumor therapy. HER2 is usually overexpressed in more than 15% GC patients, developing a reliable diagnostic tool for tumor HER2 detection is important. In this study, we attend to use polyethylene glycol (PEG) linked anti-HER2/neu peptide (AHNP-PEG) as a nuclear imaging agent probe for HER2 detection in GC xenograft animal model. Methods: The HER2 expression of human sera and tissues were detected in GC patients and normal subjects. GC cell lines NCI-N87 (high HER2 levels) and MKN45 (low HER2 levels) were treated with AHNP-PEG to assess the cell viability and HER2 binding ability. The NCI-N87 was treated with AHNP-PEG to observe the level and phosphorylation of HER2. The MKN45 and NCI-N87-induced xenograft mice were intravenous injection with fluorescence labeled AHNP-PEG for detecting in vivo fluorescence imaging properties and biodistribution. The AHNP-PEG was conjugated with diethylenetriaminopentaacetic acid (DTPA) for indium-111 labeling ( 111 In-DTPA-AHNP-PEG). The stability of was assessed in vitro. The imaging properties and biodistribution of 111 In-DTPA-AHNP-PEG were observed in NCI-N87-induced xenograft mice. Results: The serum HER2 (sHER2) levels in GC patients were significantly higher than the normal subjects. The sHER2 levels were correlated with the tumor HER2 levels in different stages of GC patients. The AHNP-PEG inhibited the cell growth and down-regulated HER2 phosphorylation in HER2-overexpressed human GC cells (NCI-N87) via specific HER2 interaction of cell surface. In addition, the GC tumor tissues from HER2-postive xenograft mice presented higher HER2 fluorescence imaging as compared to HER2-negative group. The HER2 levels in the tumor tissues were also higher than other organs in NCI-N87-induced xenograft mice. Finally, we further observed that the 111 In-DTPA-AHNP-PEG was significantly enhanced in tumor tissues of NCI-N87-induced xenograft mice compared to control. Conclusions: These findings suggest that the sHER2 measurement may be as a potential tool for detecting HER2 expressions in GC patients. The radioisotope-labeled AHNP-PEG may be useful to apply in GC patients for HER2 nuclear medicine imaging. ? 2018 The Author(s).
Subjects
Gastric cancer; HER2 overexpression; HER2-targeted peptide; Nuclear medicine imaging
SDGs
Other Subjects
epidermal growth factor receptor 2; indium 111; macrogol; pentetic acid; peptide; epidermal growth factor receptor 2; indium; Indium-111; macrogol; organometallic compound; peptide; adult; animal cell; animal experiment; animal model; animal tissue; Article; binding affinity; cancer inhibition; cancer staging; cancer tissue; cell surface; cell viability; clinical article; controlled study; down regulation; fluorescence imaging; histopathology; human; human cell; human tissue; immunohistochemistry; in vitro study; in vivo study; isotope labeling; male; MKN45 cell line; mouse; NCI-N87 cell line; nonhuman; protein blood level; protein expression; protein interaction; protein phosphorylation; stomach cancer; tumor xenograft; animal; Bagg albino mouse; blood; cell survival; chemistry; diagnostic imaging; drug screening; female; metabolism; middle aged; molecular probe; nude mouse; pathology; phosphorylation; single photon emission computed tomography; stomach tumor; tissue distribution; tumor cell line; x-ray computed tomography; Animals; Cell Line, Tumor; Cell Survival; Female; Humans; Indium Radioisotopes; Male; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Molecular Probes; Organometallic Compounds; Peptides; Phosphorylation; Polyethylene Glycols; Receptor, ErbB-2; Stomach Neoplasms; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Xenograft Model Antitumor Assays
Publisher
BioMed Central Ltd.
Type
journal article