The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer

2021 ◽  
Author(s):  
Vladimir Tolmachev ◽  
Anna Orlova ◽  
Jens Sörensen
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Her2 Expression

Molecular Imaging of Breast Cancer: Role of RGD Peptides

2015 ◽  
Vol 15 (13) ◽  
pp. 1073-1094 ◽  
Author(s):  
Rubel Chakravarty ◽  
Sudipta Chakraborty ◽  
Ashutosh Dash
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Rgd Peptides

scholarly journals HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging

2020 ◽  
Author(s):  
Betül Altunay ◽  
Agnieszka Morgenroth ◽  
Mohsen Beheshti ◽  
Andreas Vogg ◽  
Nicholas C. L. Wong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Monoclonal Antibodies ◽  
Molecular Imaging ◽  
Antibody Fragments ◽  
Drug Delivery Vehicles ◽  
Tumor Penetration ◽  
Drug Conjugates ◽  
Delivery Vehicles

Abstract Purpose The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development. Results Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients. Even in therapy, the small radioactively labeled nanobodies prove to be superior to radioactively labeled monoclonal antibodies due to their higher specificity and their ability to penetrate the tumor. Conclusion While monoclonal antibodies are well established drug delivery vehicles, the current literature on molecular imaging supports the notion that antibody fragments, such as affibodies or nanobodies, might be superior in this approach.

scholarly journals Development of the Tumor-Specific Antigen-Derived Synthetic Peptides as Potential Candidates for Targeting Breast and Other Possible Human Carcinomas

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3142 ◽  
Author(s):  
Subhani M. Okarvi ◽  
Ibrahim AlJammaz
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Tumor Antigen ◽  
Tumor Imaging ◽  
Specific Antigen ◽  
Molecular Target ◽  
Her2 Expression ◽  
Tumor Associated Antigens ◽  
Normal Tissues ◽  
Tumor Specific Antigen

The human epidermal growth factor receptor 2 (HER2) represents one of the most studied tumor-associated antigens for cancer immunotherapy. The receptors for HER2 are overexpressed in various human cancers, such as breast and ovarian cancer. The relatively low expression of this antigen on normal tissues makes it a clinically useful molecular target for tumor imaging and targeted therapy. HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcomes. Thus, HER2 has become an important prognostic and predictive factor, as well as a potential molecular target. Due to the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging is important. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in the selection of an optimal therapy. Another tumor-specific antigen is MUC1, which is silent on normal tissues, but overexpressed in almost all human epithelial cell cancers, including >90% of human breast, ovarian, pancreatic, colorectal, lung, prostate, and gastric cancers and is a promising tumor antigen with diagnostic as well as the therapeutic potential of cancer. Radiolabeled small peptide ligands are attractive as probes for molecular imaging, as they reach and bind the target receptor efficiently and clear from blood and non-target organs faster than bulky antibodies. In this study, HER2 and MUC1-based peptides were synthesized and preclinically evaluated in an effort to develop peptide-based SPECT radiopharmaceuticals derived from tumor-associated antigens for the detection of breast cancer. Our findings demonstrate that the tumor antigen peptides radiolabeled efficiently with 99mTc and showed high metabolic stability in human plasma in vitro. The data from breast tumor cell binding confirmed the high affinity (in low nanomolar range) towards respective breast cancer cell lines. In healthy mice, 99mTc-labeled peptides displayed favorable pharmacokinetics, with high excretion by the renal system. In tumor xenografts nude mice models, good uptake by the SKBR3, MCF7, and T47D tumors were found, with good tumor-to-blood and tumor to muscle ratios. Additionally, tumor lesions can be seen in γ-camera imaging. Our data suggest that based on its ability to detect HER2- and MUC1-positive breast cancer cells in vivo, 99mTc-HER2 and 99mTc-MUC1-targeted peptides may be promising tumor imaging probes and warrant further investigation.

scholarly journals First-in-Human Molecular Imaging of HER2 Expression in Breast Cancer Metastases Using the 111In-ABY-025 Affibody Molecule

2014 ◽  
Vol 55 (5) ◽  
pp. 730-735 ◽  
Author(s):  
J. Sorensen ◽  
D. Sandberg ◽  
M. Sandstrom ◽  
A. Wennborg ◽  
J. Feldwisch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Her2 Expression ◽  
Affibody Molecule ◽  
Breast Cancer Metastases ◽  
Cancer Metastases

scholarly journals HER2-intronic miR-4728-5p facilitates HER2 expression and accelerates cell proliferation and migration by targeting EBP1 in breast cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245832
Author(s):  
Yu Zhou ◽  
Yuan Yuan ◽  
Liuyi Li ◽  
Xueliang Wang ◽  
Yimin Quan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Luciferase Reporter ◽  
Her2 Expression ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

HER2 amplification greatly contributes to the tumorigenesis of multiple cancers. Intronic miR-4728-5p is transcribed along with its host gene HER2. However, little is known about the role of miR-4728-5p in cancer. This study aims to elucidate the potential role of miR-4728-5p and the underlying mechanism in breast cancer. Kaplan-Meier analysis showed that higher expression of HER2 led to worse survival outcomes in breast cancer patients. The TCGA dataset revealed that compared to normal breast tissues, HER2 and miR-4728-5p levels were significantly upregulated in breast cancer tissues with a positive correlation. In functional assays, miR-4728-5p was confirmed to promote the proliferation and migration in breast cancer cell BT474. EBP1 was identified as a direct target of miR-4728-5p via bioinformatics and luciferase reporter assays. miR-4728-5p was further demonstrated to increase HER2 expression and promote cell proliferation and migration by directly inhibiting EBP1 in breast cancer. Taken together, the HER2-intronic miR-4728-5p/EBP1/HER2 feedback loop plays an important role in promoting breast cancer cell proliferation and migration. Our study provides novel insights for targeted therapies of breast cancer.

scholarly journals Role of CXCR7 in breast cancer using molecular imaging techniques

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Bradley R. Foerster ◽  
Kathryn E. Luker ◽  
Gary D Luker
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Imaging Techniques

Correlation between different levels of HER2 expression in circulating tumor cells (cHER2 ratio) and metastatic behavior in stageIVaggressive breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3036-3036
Author(s):  
Paolo D'Amico ◽  
Carolina Reduzzi ◽  
Sara Gandini ◽  
Lorenzo Gerratana ◽  
Wenan Qiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Spread ◽  
Metastatic Spread ◽  
Her2 Expression ◽  
Prognostic Role ◽  
Metastatic Site

3036 Background: The presence of HER2 expressing (HER2+) circulating tumor cells (CTCs) occurs often in metastatic breast cancer (MBC) patients (pts). We have previously showed that the ratio among CTCs expressing high level of HER2 and the total number of HER2+ CTCs (circulating HER2 ratio, cHer2 ratio) has a prognostic role in MBC patients. Here we further investigate the role of the cHER2 ratio in the process of metastatic spread. Methods: Under IRB-approved study we prospectively analyzed blood samples of patients with MBC enrolled before starting a new line of therapy. Samples were collected from pts treated at Northwestern University (Chicago, IL) between 2016 and 2020. CTCs were enumerated through CellSearch (Menarini Silicon Biosystems, Bologna, Italy) and characterized for HER2 expression using the CellSearch CXC Kit. HER2+ CTCs were divided in 3 different categories (1+,2+,3+) leaning on fluorescence intensity. Pts with <5 CTCs (stage IV indolent) were excluded from the analysis. The cHER2 ratio, defined as the sum of 2+ CTCs and 3+ CTCs divided by the total number of HER2+ CTCs, was used to split the remaining pts in 2 different cohorts: cHER2 ratio high (> 0.75) (cHER2high) and cHER2 ratio low (≤0.75) (cHER2low). The frequency of each metastatic site (i.e. liver, lung, central nervous system, bone, lymph nodes, skin/soft tissue, serosa) and the total number of different sites involved (1-7, ≤2 and >2 sites) were compared among the two sub-populations and analyzed through Fisher exact test. Results: Out of 98 pts enrolled, 77 were classified as cHER2low and 21 as cHER2high. We observed a higher frequency of oligometastatic pts (≤2 sites involved) in the cHER2high cohort (16, 76%), compared to only 29 (37%) in the cHER2low (p<0.005). Moreover, the cHER2 ratio was associated with a tropism toward specific sites of disease spread with higher incidence of liver, lung and lymph nodes metastases in the cHER2low cohort (p<0.05). No other statistical associations were observed in respect of specific organ tropism. The frequency of involvement for each metastatic site among the two cohorts are reported in the table. Conclusions: Measuring CTCs enumeration and HER2 expression we identified two cohorts, cHER2high and cHER2low, associated with distinct patterns of metastatic spread. The cHER2low pts were correlated to multiple sites of metastatic involvement, with particular tropism toward liver, lung and lymph nodes. These results confirm the prognostic role of the cHER2 ratio, suggesting a peculiar biological meaning of the HER2+ 1+ CTCs.[Table: see text]

Sign in / Sign up

Export Citation Format

Share Document