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

Aram S A van Brussel, Arthur Adams, Sabrina Oliveira, Bram Dorresteijn, Mohamed El Khattabi, Jeroen F. Vermeulen, Elsken van der Wall, W.P.T.M. Mali, Patrick W B Derksen, Paul J. van Diest, Paul M P van Bergen En Henegouwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)535
Number of pages544
JournalMolecular Imaging and Biology
Volume18
Issue number4
DOIs
Publication statusPublished - Aug 2016

Keywords

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

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