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- Title
Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.
- Authors
Brussel, Aram; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; Khattabi, Mohamed; Vermeulen, Jeroen; Wall, Elsken; Mali, Willem; Derksen, Patrick; Diest, Paul; Bergen en Henegouwen, Paul; van Brussel, Aram S A; El Khattabi, Mohamed; Vermeulen, Jeroen F; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P
- Abstract
<bold>Purpose: </bold>The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.<bold>Procedures: </bold>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).<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
HYPOXEMIA; MAMMOGRAMS; BREAST cancer; CARCINOGENS; XENOGRAFTS; DNA metabolism; ADENOCARCINOMA; ANIMAL experimentation; CANCER invasiveness; CELL physiology; CELLS; DIAGNOSTIC imaging; GENETIC engineering; IMMUNIZATION; IMMUNOGLOBULINS; IMMUNOHISTOCHEMISTRY; MICE; MOLECULAR diagnosis
- Publication
Molecular Imaging & Biology, 2016, Vol 18, Issue 4, p535
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-015-0909-6