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Mol Imaging Biol. 2016 Aug;18(4):535-44. doi: 10.1007/s11307-015-0909-6.

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

Author information

1
Division of Cell Biology, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
2
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
3
Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
4
QVQ BV, Utrecht, The Netherlands.
5
Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
6
Division of Cell Biology, Department of Biology, Science Faculty, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. p.vanbergen@uu.nl.

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.

KEYWORDS:

Breast cancer; Carbonic anhydrase IX; Molecular fluorescence pathology; Nanobody; Optical imaging; VHH

PMID:
26589824
PMCID:
PMC4927611
DOI:
10.1007/s11307-015-0909-6
[Indexed for MEDLINE]
Free PMC Article

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