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Magnetic resonance molecular imaging of the HER-2/neu receptor
Dmitri Artemov1, Noriko Mori, Rajani Ravi
1Departments of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dmitri@mri.jhu.edu
Abstract:
The HER-2/neu receptor is a member of the epidermal growth factor family and is amplified in multiple cancers. It is under intense investigation both as a prognostic marker and for therapy, using monoclonal antibodies targeted against the receptor. We have developed a novel two-component gadolinium-based MR contrast agent to image the HER-2/neu receptor. Positive T1 contrast in MR images was generated by the specific binding of avidin-gadolinium complexes to tumor cells prelabeled with a biotinylated anti-HER-2/neu antibody. Significant intensity enhancement was observed in HER-2/neu-expressing cell lines and in vivo in a breast cancer model. Potential applications of this approach may include determination of the HER-2/neu status for prognosis and for selecting tumors for monoclonal antibody therapy.
Insights
Researchers developed a novel gadolinium-based contrast agent for Magnetic Resonance Imaging (MRI) to detect the HER-2/neu receptor in cancer. This imaging agent shows promise for cancer prognosis and guiding targeted therapy.
Area of Science:
- Oncology
- Biomedical Imaging
- Molecular Biology
Background:
- The HER-2/neu receptor is amplified in several cancers and is a target for prognostic and therapeutic strategies.
- Monoclonal antibodies are currently used for HER-2/neu targeted therapy.
Purpose of the Study:
- To develop a novel gadolinium-based contrast agent for Magnetic Resonance Imaging (MRI) to visualize the HER-2/neu receptor.
- To assess the efficacy of this agent in detecting HER-2/neu-expressing cells and tumors.
Main Methods:
- A two-component contrast agent was developed, utilizing avidin-gadolinium complexes.
- Tumor cells were pre-labeled with a biotinylated anti-HER-2/neu antibody.
- MRI was performed to observe T1 contrast enhancement upon specific binding.
Main Results:
- Specific binding of the avidin-gadolinium complex to pre-labeled tumor cells generated positive T1 contrast.
- Significant intensity enhancement was observed in HER-2/neu-expressing cell lines.
- In vivo studies in a breast cancer model demonstrated successful imaging.
Conclusions:
- The developed gadolinium-based MR contrast agent can effectively image HER-2/neu receptor expression.
- This approach holds potential for determining HER-2/neu status for cancer prognosis.
- It may also aid in selecting tumors suitable for monoclonal antibody therapy.