The emerging role of radionuclide molecular imaging of HER2 expression in breast cancer
Vladimir Tolmachev1, Anna Orlova2, Jens Sörensen3
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk, Russia.
Abstract:
Targeting of human epidermal growth factor type 2 (HER2) using monoclonal antibodies, antibody-drug conjugates and tyrosine kinase inhibitors extends survival of patients with HER2-expressing metastatic breast cancer. High expression of HER2 is a predictive biomarker for such specific treatment. Accurate determination of HER2 expression level is necessary for stratification of patients to targeted therapy. Non-invasive in vivo radionuclide molecular imaging of HER2 has a potential of repetitive measurements, addressing issues of heterogeneous expression and conversion of HER2 status during disease progression or in response to therapy. Imaging probes based of several classes of targeting proteins are currently in preclinical and early clinical development. Both preclinical and clinical data suggest that the most promising are imaging agents based on small proteins, such as single domain antibodies or engineered scaffold proteins. These agents permit a very specific high-contrast imaging at the day of injection.
Insights
Non-invasive molecular imaging of human epidermal growth factor type 2 (HER2) using small protein agents offers precise, high-contrast visualization. This approach aids in patient stratification for targeted HER2-positive metastatic breast cancer therapies.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Targeting human epidermal growth factor type 2 (HER2) with therapies like monoclonal antibodies improves survival in HER2-expressing metastatic breast cancer.
- HER2 expression is a key predictive biomarker for guiding targeted treatment decisions.
- Accurate HER2 expression assessment is crucial for patient stratification in targeted therapy.
Purpose of the Study:
- To explore the potential of non-invasive in vivo radionuclide molecular imaging for assessing HER2 expression.
- To address challenges in HER2 assessment, including heterogeneous expression and status conversion during treatment.
- To evaluate novel imaging probes for HER2-targeted molecular imaging.
Main Methods:
- Development and preclinical/clinical evaluation of imaging probes targeting HER2.
- Utilizing various targeting proteins, with a focus on small proteins like single domain antibodies and engineered scaffold proteins.
- Assessing the specificity and contrast of imaging agents for in vivo HER2 visualization.
Main Results:
- Small protein-based imaging agents demonstrate high specificity and contrast for HER2.
- These agents enable high-quality imaging on the day of injection.
- Promising preclinical and early clinical data support their utility.
Conclusions:
- Non-invasive HER2 imaging agents, particularly those based on small proteins, are highly promising for clinical application.
- Repetitive imaging can monitor HER2 status, aiding treatment management.
- These agents facilitate accurate patient stratification for HER2-targeted therapies.
