TY - JOUR
T1 - Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer
AU - van Brussel, Aram S.A.
AU - Adams, Arthur
AU - Oliveira, Sabrina
AU - Dorresteijn, Bram
AU - El Khattabi, Mohamed
AU - Vermeulen, Jeroen F.
AU - van der Wall, Elsken
AU - Mali, Willem P.Th M.
AU - Derksen, Patrick W.B.
AU - van Diest, Paul J.
AU - van Bergen en Henegouwen, Paul M.P.
N1 - Funding Information:
We would like to thank QVQ BV for the expression plasmid of cysteine-functionalized VHH/nanobodies and P.C. Pearlman for writing the image analysis algorithm in Matlab. We are indebted to S.G. Elias for suggestions concerning the mouse model. We would also like to thank the animal facility of the University Utrecht and the biobank of the University Medical Center Utrecht. This research was supported by the Center for Translational Molecular Medicine - Mammary Carcinoma Molecular Imaging for Diagnosis and Therapeutics (CTMM-MAMMOTH, project 203), and by an unrestricted educational grant from Aegon to PJvD and EvdW.
Publisher Copyright:
© 2015, The Author(s).
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Carbonic anhydrase IX
KW - Molecular fluorescence pathology
KW - Nanobody
KW - Optical imaging
KW - VHH
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U2 - 10.1007/s11307-015-0909-6
DO - 10.1007/s11307-015-0909-6
M3 - Article
C2 - 26589824
AN - SCOPUS:84947728596
SN - 1536-1632
VL - 18
SP - 535
EP - 544
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 4
ER -