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Published on: June 18, 2013
Spectral fluorescence molecular imaging of lung metastases targeting HER2/neu
Yoshinori Koyama1, Yukihiro Hama, Yasuteru Urano
1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1088, USA.
Purpose:
Surgical resection of pulmonary metastases is now a clinically accepted cancer therapy but its success depends on the accurate localization and removal of all tumor foci. To enhance the detection of pulmonary metastases during surgery, we developed an i.v. administered optical probe that uses a monoclonal antibody, Herceptin (trastuzumab), conjugated to a fluorophore, rhodamine green (RhodG), to specifically detect human epidermal growth factor receptor type 2 (HER2/neu)-expressing pulmonary lesions in an animal model of lung metastases.
Experimental Design:
Pulmonary metastases were induced by i.v. injection of gene-transfected murine embryonic fibroblasts (3T3) cells in a murine model to produce a mixed population of HER2+ and HER2- tumors. To image these tumors, an anti-HER2 (Herceptin) or a control (HUT) complementarity-determining region-grafted antibody was conjugated to RhodG and injected i.v. into mice. Spectral fluorescence imaging was done after thoracotomy and images were correlated with gross and microscopic pathology to assess sensitivity and specificity.
Results:
HER2+ tumors injected with Herceptin-RhodG were more fluorescent than either HER2- tumors or HER2+ tumors injected with HUT-RhodG at all time points. The maximal fluorescence signal in HER2+ tumors injected with Herceptin-RhodG was observed at 1 day postinjection. The tumors fluoresced primarily at the rim and not their center, reflecting the binding-site barrier that is commonly seen with high-affinity antibodies.
Conclusion:
A HER2-targeted optical imaging probe shows the ability to specifically enhance HER2+ pulmonary metastases but not HER2- pulmonary metastases. The high sensitivity and specificity of this probe is encouraging for the development of antigen-targeted optical probes to assist in the resection of pulmonary metastases.
Insights
A novel optical imaging probe specifically detects HER2-positive lung tumors using Herceptin (trastuzumab) conjugated to a fluorophore. This targeted approach enhances the visualization of pulmonary metastases, aiding surgical resection.
Area of Science:
- Oncology
- Medical Imaging
- Molecular Biology
Background:
- Accurate localization of pulmonary metastases is crucial for successful surgical resection.
- Current methods may not sufficiently detect all tumor foci during surgery.
- Targeted molecular imaging offers a potential solution for enhanced tumor detection.
Purpose of the Study:
- To develop and evaluate an i.v. administered optical probe for specific detection of HER2/neu-expressing pulmonary metastases.
- To utilize Herceptin (trastuzumab) conjugated to rhodamine green (RhodG) for targeted imaging.
- To assess the probe's sensitivity and specificity in a preclinical lung metastases model.
Main Methods:
- Pulmonary metastases were induced in mice using gene-transfected murine embryonic fibroblasts.
- A mixed population of HER2-positive (HER2+) and HER2-negative (HER2-) tumors were generated.
- Spectral fluorescence imaging was performed after i.v. injection of Herceptin-RhodG or a control antibody, followed by pathological correlation.
Main Results:
- HER2+ tumors exhibited significantly higher fluorescence when injected with Herceptin-RhodG compared to HER2- tumors or control antibody.
- Maximal fluorescence signal in HER2+ tumors was observed one day post-injection.
- Fluorescence was primarily localized at the tumor rim, indicating antibody binding characteristics.
Conclusions:
- The HER2-targeted optical imaging probe specifically enhances the detection of HER2+ pulmonary metastases.
- The probe demonstrated high sensitivity and specificity in a preclinical model.
- This targeted imaging approach holds promise for improving surgical resection of pulmonary metastases.
