TY - JOUR
T1 - Near-Infrared Fluorescence Molecular Imaging of Ductal Carcinoma in Situ with CD44v6-Specific Antibodies in Mice
T2 - A Preclinical Study
AU - Vermeulen, Jeroen F.
AU - Van Brussel, Aram S.A.
AU - Adams, Arthur
AU - Mali, Willem P.Th M.
AU - Van Der Wall, Elsken
AU - Van Diest, Paul J.
AU - Derksen, Patrick W.B.
N1 - Funding Information:
Acknowledgments. We would like to thank G. van der Pluijm for providing the luciferase-expressing MDA-MB-231 cells and A. Martens for the pLV-CMV-LUC2-IRES-GFP vector. M. van Amersfoort is acknowledged for the expert technical assistance with the mouse experiments. We are also indebted to the UMC Utrecht biobank for their support. This work was supported by an unrestricted research grant of AEGON Inc. and by the Mammary Carcinoma Molecular imaging for diagnostics and Therapeutics project of the Dutch Center for Translational Molecular Medicine.
PY - 2013/6
Y1 - 2013/6
N2 - Purpose: The purpose of this study was to develop a molecular imaging technique using tracers specific for ductal carcinoma in situ (DCIS) to improve visualization and localization of DCIS during surgery. As CD44v6 is frequently expressed in DCIS, we used near-infrared fluorescently labeled CD44v6-targeting antibodies for detection of DCIS. Procedure: Mice bearing orthotopically transplanted CD44v6-positive MCF10DCIS DCIS-like tumors and CD44v6-negative MDA-MB-231 control tumors were intravenously injected with IRDye800CW conjugated to CD44v6-specific antibodies or control IgGs. Noninvasive imaging was performed for 8 days postinjection, followed by intraoperative imaging. Antibody accumulation and intratumor distribution were examined. Results: Maximum accumulation of CD44v6-specific antibodies was obtained 24 h postinjection. Maximum tumor-to-background ratio for MCF10DCIS tumors was 4.5 ± 0.2, compared to 1.4 ± 0.1 (control tumors, p = 0.006), and 1.7 ± 0.1 (control IgG, p = 0.014), for 8 days postinjection. Ex vivo, tumor-to-background ratios were comparable to those obtained by intraoperative imaging. Conclusions: We show the applicability of noninvasive and intraoperative optical imaging of DCIS-like lesions in vivo using CD44v6-specific antibodies.
AB - Purpose: The purpose of this study was to develop a molecular imaging technique using tracers specific for ductal carcinoma in situ (DCIS) to improve visualization and localization of DCIS during surgery. As CD44v6 is frequently expressed in DCIS, we used near-infrared fluorescently labeled CD44v6-targeting antibodies for detection of DCIS. Procedure: Mice bearing orthotopically transplanted CD44v6-positive MCF10DCIS DCIS-like tumors and CD44v6-negative MDA-MB-231 control tumors were intravenously injected with IRDye800CW conjugated to CD44v6-specific antibodies or control IgGs. Noninvasive imaging was performed for 8 days postinjection, followed by intraoperative imaging. Antibody accumulation and intratumor distribution were examined. Results: Maximum accumulation of CD44v6-specific antibodies was obtained 24 h postinjection. Maximum tumor-to-background ratio for MCF10DCIS tumors was 4.5 ± 0.2, compared to 1.4 ± 0.1 (control tumors, p = 0.006), and 1.7 ± 0.1 (control IgG, p = 0.014), for 8 days postinjection. Ex vivo, tumor-to-background ratios were comparable to those obtained by intraoperative imaging. Conclusions: We show the applicability of noninvasive and intraoperative optical imaging of DCIS-like lesions in vivo using CD44v6-specific antibodies.
KW - Antibody
KW - Breast cancer
KW - DCIS
KW - IRDye800CW
KW - Mouse model
KW - NIRF
KW - Optical imaging
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U2 - 10.1007/s11307-012-0605-8
DO - 10.1007/s11307-012-0605-8
M3 - Article
C2 - 23184608
AN - SCOPUS:84877784814
SN - 1536-1632
VL - 15
SP - 290
EP - 298
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 3
ER -