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Updated: Mar 29, 2026
In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model
Published on: October 3, 2011
Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
Aram S A van Brussel1,2, Arthur Adams3, Sabrina Oliveira1,2
1Division of Cell Biology, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Purpose:
The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.
Procedures:
CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).
Results:
Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3 ± 0.6, compared to a TNR of 1.4 ± 0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8 ± 0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0 ± 1.1 %I.D./g in DCIS + CAIX tumors, 4.6 ± 0.8 %I.D./g in DCIS tumors, while 2.0 ± 0.2 %I.D./g was obtained with R2-IR.
Conclusions:
These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.
Insights
Researchers developed a novel Carbonic Anhydrase IX (CAIX)-specific nanobody conjugated to IRDye800CW for molecular imaging. This tool enables rapid detection of pre-invasive breast cancer, showing promising tumor-to-normal tissue ratios in preclinical models.
Area of Science:
- Molecular Imaging
- Nanotechnology
- Oncology
Background:
- Early detection of breast cancer is crucial for effective treatment.
- Pre-invasive breast cancer, such as ductal carcinoma in situ (DCIS), presents diagnostic challenges.
- Targeted molecular imaging agents can improve diagnostic accuracy.
Purpose of the Study:
- To develop a Carbonic Anhydrase IX (CAIX)-specific nanobody.
- To conjugate the nanobody to the near-infrared dye IRDye800CW for imaging.
- To evaluate the efficacy of this conjugate for molecular imaging of pre-invasive breast cancer.
Main Methods:
- Selection of CAIX-specific nanobodies using modified phage display.
- Site-specific conjugation of nanobodies to IRDye800CW.
- Evaluation in a xenograft mouse model using DCIS cells.
- Assessment of tumor-to-normal tissue ratios (TNR) and biodistribution.
Main Results:
- Specific anti-CAIX nanobodies were successfully generated.
- The CAIX-specific nanobody-IRDye800CW conjugate achieved a mean TNR of 4.3 ± 0.6 in DCIS xenografts overexpressing CAIX.
- Biodistribution studies showed significant uptake in DCIS + CAIX tumors (14.0 ± 1.1 %I.D./g).
Conclusions:
- A CAIX-specific nanobody-IRDye800CW conjugate was successfully developed.
- This conjugate demonstrates potential for rapid molecular imaging of pre-invasive breast cancer.
- The findings support its use in preclinical breast cancer imaging.
