Dataset Information

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.

ABSTRACT:

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.

SUBMITTER: van Brussel AS

PROVIDER: S-EPMC4927611 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.

van Brussel Aram S A AS Adams Arthur A Oliveira Sabrina S Dorresteijn Bram B El Khattabi Mohamed M Vermeulen Jeroen F JF van der Wall Elsken E Mali Willem P Th M WP Derksen Patrick W B PW van Diest Paul J PJ van Bergen En Henegouwen Paul M P PM

Molecular imaging and biology 20160801 4

<h4>Purpose</h4>The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.<h4>Procedures</h4>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).<h4>Results</h4>Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody ...[more]

PMID: 26589824

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Project description:BACKGROUND:Optical molecular imaging is an emerging novel technology with applications in the diagnosis of cancer and assistance in image-guided surgery. A high tumour-to-background (T/B) ratio is crucial for successful imaging, which strongly depends on tumour-specific probes that rapidly accumulate in the tumour, while non-bound probes are rapidly cleared. Here, using pre-invasive breast cancer as a model, we investigate whether the use of combinations of probes with different target specificities results in higher T/B ratios and whether dual-spectral imaging leads to improvements in tumour characterization. METHODS:We performed optical molecular imaging of an orthotopic breast cancer model mimicking ductal carcinoma in situ (DCIS). A combination of carbonic anhydrase IX (CAIX)- and human epidermal growth factor receptor 2 (HER2)-specific variable domains of the heavy chain from heavy-chain antibodies (VHHs) was conjugated either to the same fluorophore (IRDye800CW) to evaluate T/B ratios or to different fluorophores (IRDye800CW, IRDye680RD or IRDye700DX) to analyse the expression of CAIX and HER2 simultaneously through dual-fluorescence detection. These experiments were performed non-invasively in vivo, in a mimicked intra-operative setting, and ex vivo on tumour sections. RESULTS:Application of the CAIX- and HER2-specific VHH combination resulted in an increase of the T/B ratio, as compared to T/B ratios obtained from each of these single VHHs together with an irrelevant VHH. This dual tumour marker-specific VHH combination also enabled the detection of small metastases in the lung. Furthermore, dual-spectral imaging enabled the assessment of the expression status of both CAIX and HER2 in a mimicked intra-operative setting, as well as on tumour sections, which was confirmed by immunohistochemistry. CONCLUSIONS:These results establish the feasibility of the use of VHH 'cocktails' to increase T/B ratios and improve early detection of heterogeneous tumours and the use of multispectral molecular imaging to facilitate the assessment of the target expression status of tumours and metastases, both invasive or non-invasively.

Dataset Information

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.

Purpose

Procedures

Results

Conclusions

Publications

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.

Similar Datasets

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