Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery

Kijanka M, Warnders FJ, El Khattabi M, Lub-De Hooge M, Van Dam GM, Ntziachristos V, De Vries L, Oliveira S, Van Bergen En Henegouwen PMP (2013)

Publication Type: Journal article

Publication year: 2013

Journal

European Journal of Nuclear Medicine and Molecular Imaging Springer Verlag (Germany)

Book Volume: 40

Pages Range: 1718-1729

Journal Issue: 11

DOI: 10.1007/s00259-013-2471-2

Abstract

Purpose: Molecular optical imaging using monoclonal antibodies is slow with low tumour to background ratio. We used anti-HER2 VHHs conjugated to IRDye 800CW to investigate their potential as probes for rapid optical molecular imaging of HER2-positive tumours by the determination of tumour accumulation and tumour to background levels. Methods: Three anti-HER2 VHHs (11A4, 18C3, 22G12) were selected with phage display and produced in Escherichia coli. Binding affinities of these probes to SKBR3 cells were determined before and after site-specific conjugation to IRDye 800CW. To determine the potential of VHH-IR as imaging probes, serial optical imaging studies were carried out using human SKBR3 and human MDA-MB-231 xenograft breast cancer models. Performance of the anti-HER2 VHH-IR was compared to that of trastuzumab-IR and a non-HER2-specific VHH-IR. Image-guided surgery was performed during which SKBR3 tumour was removed under the guidance of the VHH-IR signal. Results: Site-specific conjugation of IRDye 800CW to three anti-HER2 VHHs preserved high affinity binding with the following dissociation constants (KD): 11A4 1.9 ± 0.03, 18C3 14.3 ± 1.8 and 22G12 3.2 ± 0.5 nM. Based upon different criteria such as binding, production yield and tumour accumulation, 11A4 was selected for further studies. Comparison of 11A4-IR with trastuzumab-IR showed ∼20 times faster tumour accumulation of the anti-HER2 VHH, with a much higher contrast between tumour and background tissue (11A4-IR 2.5 ± 0.3, trastuzumab-IR 1.4 ± 0.4, 4 h post-injection). 11A4-IR was demonstrated to be a useful tool in image-guided surgery. Conclusion: VHH-IR led to a much faster tumour accumulation with high tumour to background ratios as compared to trastuzumab-IR allowing same-day imaging for clinical investigation as well as image-guided surgery. © 2013 Springer-Verlag Berlin Heidelberg.

Involved external institutions

Universiteit Utrecht (UU) / Utrecht University NL Netherlands (NL) University of Groningen / Rijksuniversiteit Groningen NL Netherlands (NL) QVQuality NL Netherlands (NL) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen NL Netherlands (NL) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Kijanka, M., Warnders, F.-J., El Khattabi, M., Lub-De Hooge, M., Van Dam, G.M., Ntziachristos, V.,... Van Bergen En Henegouwen, P.M.P. (2013). Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery. European Journal of Nuclear Medicine and Molecular Imaging, 40(11), 1718-1729. https://doi.org/10.1007/s00259-013-2471-2

MLA:

Kijanka, Marta, et al. "Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery." European Journal of Nuclear Medicine and Molecular Imaging 40.11 (2013): 1718-1729.

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