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, W.P.T.M.
AU - Derksen, Patrick W B
AU - van Diest, Paul J.
AU - van Bergen En Henegouwen, Paul M P
PY - 2016/8
Y1 - 2016/8
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 - Carbonic anhydrase IX
KW - Nanobody
KW - VHH
KW - Optical imaging
KW - Molecular fluorescence pathology
KW - Breast cancer
UR - http://www.scopus.com/inward/record.url?scp=84947728596&partnerID=8YFLogxK
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
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 4
ER -