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, Willem P.Th M. Mali, Patrick W.B. Derksen, Paul J. van Diest, Paul M.P. van Bergen en Henegouwen

Research output: Contribution to journalArticlepeer-review

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 (US)
Pages (from-to)535-544
Number of pages10
JournalMolecular Imaging and Biology
Volume18
Issue number4
DOIs
StatePublished - Aug 1 2016

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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