Metastatic breast cancer is incurable. The goal of this stu
dy was to
develop a positron emission tomography (PET)/near-infrare
d fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibo
dy, was
dual-labele
d with a NIRF
dye (IRDye 800CW) an
d 89Zr to yiel
d 89Zr-Df-TRC105-800CW. Luciferase-transfecte
d 4T1 murine breast cancer cells were injecte
d intravenously into female mice to establish the tumor mo
del. Bioluminescence imaging (BLI) was carrie
d out to noninvasively monitor the lung tumor bur
den. PET imaging reveale
d that 4T1 lung tumor uptake of
89Zr-Df-TRC105-800CW was 8.7 卤 1.4, 10.9 卤 0.5, an
d 9.7 卤 1.1% ID/g at 4, 24, an
d 48 h postinjection (
n = 4), with excellent tumor contrast. Bio
distribution stu
dies, blocking, control stu
dies with
89Zr-Df-cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, an
d histology all confirme
d CD105 specificity of the tracer. Broa
d clinical potential of TRC105-base
d agents was shown in many tumor types, which also enable
d early
detection of small metastasis an
d intraoperative gui
dance for tumor removal.
Keywords:
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=breast+cancer&qsSearchArea=searchText">breast cancer;
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=lung+metastasis&qsSearchArea=searchText">lung metastasis;
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=positron+emission+tomography+%5C%28PET%5C%29&qsSearchArea=searchText">positron emission tomography (PET);
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=near%5C-infrared+fluorescence+%5C%28NIRF%5C%29&qsSearchArea=searchText">near-infrared fluorescence (NIRF);
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=tumor+angiogenesis&qsSearchArea=searchText">tumor angiogenesis;
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=CD105+%5C%28endoglin%5C%29&qsSearchArea=searchText">CD105 (endoglin);
d="authors" href="http://pubs.acs.org/action/doSearch?action=search&searchText=89Zr&qsSearchArea=searchText">89Zr