Related Experiment Video
Updated: Oct 31, 2025
Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors
Published on: June 18, 2013
Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer
Solmaz AghaAmiri1, Jo Simien1, Alastair M Thompson2,3
1The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, TX 77054, USA.
Background:
Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS).
Methods:
mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging.
Results:
In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues.
Conclusions:
We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.
Insights
Fluorescently labeled trastuzumab and pertuzumab antibodies enable near-infrared imaging for detecting residual HER2-positive breast cancer. This research demonstrates their potential for image-guided surgery, improving residual disease detection.
Area of Science:
- Oncology
- Medical Imaging
- Biotechnology
Background:
- Advances in HER2-positive breast cancer therapy improve survival but residual disease detection remains difficult.
- Targeted therapies like monoclonal antibodies (mAbs) offer potential for improved diagnostics.
- Fluorescence-guided surgery (FGS) requires reliable imaging agents for residual disease visualization.
Purpose of the Study:
- To evaluate anti-HER2 monoclonal antibodies (mAbs) trastuzumab and pertuzumab as immunoconjugates for fluorescence-guided surgery.
- To assess the feasibility of using these agents for detecting residual HER2-positive breast cancer.
- To compare the near-infrared fluorescent (NIRF) imaging performance of trastuzumab and pertuzumab immunoconjugates.
Main Methods:
- Conjugation of trastuzumab and pertuzumab mAbs to the NIRF dye IRDye800.
- Dual labeling with 89Zr for quantitative in vitro assessment.
- In vitro binding assays in HER2-overexpressing and HER2-negative cell lines.
- In vivo and ex vivo fluorescence imaging using BT474 and MCF7 xenografts.
Main Results:
- Both fluorescent immunoconjugates demonstrated HER2-mediated binding in vitro.
- In vivo and ex vivo imaging showed preferential accumulation of fluorescent mAbs in tumors.
- Similar tumor-to-background ratios were achieved for both agents.
- Immunohistochemical staining confirmed in vivo HER2 specificity.
Conclusions:
- Fluorescent trastuzumab and pertuzumab immunoconjugates exhibit comparable NIRF imaging performance.
- This study demonstrates the potential for HER2-targeted fluorescence-guided surgery.
- Agents with distinct epitope specificities can be developed for effective image-guided interventions.
