Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW.
Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and (89)Zr to yield (89)Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female mice to establish the tumor model. Bioluminescence imaging (BLI) was carried out to noninvasively monitor the lung tumor burden. PET imaging revealed that 4T1 lung tumor uptake of (89)Zr-Df-TRC105-800CW was 8.7 ± 1.4, 10.9 ± 0.5, and 9.7 ± 1.1% ID/g at 4, 24, and 48 h postinjection (n = 4), with excellent tumor contrast. Biodistribution studies, blocking, control studies with (89)Zr-Df-cetuximab-800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD105 specificity of the tracer. Broad clinical potential of TRC105-based agents was shown in many tumor types, which also enabled early detection of small metastasis and intraoperative guidance for tumor removal.
Department of Radiology, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
Hao
H
Hong
Yin
Y
Zhang
Gregory W
GW
Severin
Yunan
Y
Yang
Jonathan W
JW
Engle
Gang
G
Niu
Robert J
RJ
Nickles
Xiaoyuan
X
Chen
Bryan R
BR
Leigh
Todd E
TE
Barnhart
Weibo
W
Cai
D000818:Animals; D001557:Benzenesulfonates / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000150:complications* / Q000175:diagnosis*; D051379:Mice; D008807:Mice, Inbred BALB C; D015040:Zirconium / Q000737:chemistry
D001557:Benzenesulfonates; C562366:IRDye 800CW; D007211:Indoles; D015040:Zirconium