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Am J Transl Res 2012;4(3):333-346
Original Article
ImmunoPET and near-infrared fluorescence imaging of CD105
expression using a monoclonal antibody dual-labeled with 89Zr and
IRDye 800CW
Yin Zhang, Hao Hong, Gregory W Severin, Jonathan W Engle, Yunan Yang, Shreya Goel, Alex J Nathanson, Glenn
Liu, Robert J Nickles, Bryan R Leigh, Todd E Barnhart, Weibo Cai
Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA; Department of Radiology,
University of Wisconsin - Madison, Madison, WI, USA; Centre of Nanotechnology, Indian Institute of Technology,
Roorkee, India; Department of Medicine, University of Wisconsin - Madison, Madison, WI, USA; University of
Wisconsin Carbone Cancer Center, Madison, WI, USA; TRACON Pharmaceuticals, Inc., San Diego, CA, USA;
Contributed equally to this work
Received July 9, 2012; accepted July 25, 2012; Epub July 27, 2012; Published August 15, 2012
Abstract: CD105 (endoglin) is an independent marker for poor prognosis in more than 10 solid tumor types. The
goal of this study was to develop a CD105-specific agent for both positron emission tomography (PET) and
near-infrared fluorescence (NIRF) imaging, which has potential clinical applications in the diagnosis and
imaged-guided resection of solid tumors. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated
to a NIRF dye (800CW) and p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) before 89Zr-labeling. Another
chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis revealed no difference in
CD105 binding affinity/specificity between TRC105 and Df-TRC105-800CW. Serial PET imaging revealed that the
4T1 tumor uptake of 89Zr-Df-TRC105-800CW was 6.3 ± 1.9, 12.3 ± 1.3, and 11.4 ± 1.1 %ID/g at 4, 24, and 48 h
post-injection (p.i.) respectively (n = 3), higher than all organs starting from 24 h p.i., which provided excellent
tumor contrast. Tumor uptake as measured by both in vivo and ex vivo NIRF imaging had a linear correlation with
the %ID/g values obtained from PET, corroborated by biodistribution studies. Blocking experiments, control
studies with 89Zr-Df-cetuximab-800CW, and histology all confirmed the CD105 specificity of
89Zr-Df-TRC105-800CW. In conclusion, herein we report dual-modality PET and NIRF imaging of CD105
expression in a breast cancer model, where CD105-specific uptake of 89Zr-Df-TRC105-800CW in the tumor was
observed. (AJTR1207002).
Keywords: CD105/endoglin, positron emission tomography (PET), near-infrared fluorescence (NIRF), tumor
angiogenesis, 89Zr, TRC105
Address all correspondence to:
Dr. Weibo Cai
Departments of Radiology and Medical Physics
University of Wisconsin - Madison, Room 7137
1111 Highland Ave, Madison, WI 53705-2275, USA.
Tel: 608-262-1749; Fax: 608- 265-0614
E-mail: wcai@uwhealth.org
Original Article
ImmunoPET and near-infrared fluorescence imaging of CD105
expression using a monoclonal antibody dual-labeled with 89Zr and
IRDye 800CW
Yin Zhang, Hao Hong, Gregory W Severin, Jonathan W Engle, Yunan Yang, Shreya Goel, Alex J Nathanson, Glenn
Liu, Robert J Nickles, Bryan R Leigh, Todd E Barnhart, Weibo Cai
Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA; Department of Radiology,
University of Wisconsin - Madison, Madison, WI, USA; Centre of Nanotechnology, Indian Institute of Technology,
Roorkee, India; Department of Medicine, University of Wisconsin - Madison, Madison, WI, USA; University of
Wisconsin Carbone Cancer Center, Madison, WI, USA; TRACON Pharmaceuticals, Inc., San Diego, CA, USA;
Contributed equally to this work
Received July 9, 2012; accepted July 25, 2012; Epub July 27, 2012; Published August 15, 2012
Abstract: CD105 (endoglin) is an independent marker for poor prognosis in more than 10 solid tumor types. The
goal of this study was to develop a CD105-specific agent for both positron emission tomography (PET) and
near-infrared fluorescence (NIRF) imaging, which has potential clinical applications in the diagnosis and
imaged-guided resection of solid tumors. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated
to a NIRF dye (800CW) and p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) before 89Zr-labeling. Another
chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis revealed no difference in
CD105 binding affinity/specificity between TRC105 and Df-TRC105-800CW. Serial PET imaging revealed that the
4T1 tumor uptake of 89Zr-Df-TRC105-800CW was 6.3 ± 1.9, 12.3 ± 1.3, and 11.4 ± 1.1 %ID/g at 4, 24, and 48 h
post-injection (p.i.) respectively (n = 3), higher than all organs starting from 24 h p.i., which provided excellent
tumor contrast. Tumor uptake as measured by both in vivo and ex vivo NIRF imaging had a linear correlation with
the %ID/g values obtained from PET, corroborated by biodistribution studies. Blocking experiments, control
studies with 89Zr-Df-cetuximab-800CW, and histology all confirmed the CD105 specificity of
89Zr-Df-TRC105-800CW. In conclusion, herein we report dual-modality PET and NIRF imaging of CD105
expression in a breast cancer model, where CD105-specific uptake of 89Zr-Df-TRC105-800CW in the tumor was
observed. (AJTR1207002).
Keywords: CD105/endoglin, positron emission tomography (PET), near-infrared fluorescence (NIRF), tumor
angiogenesis, 89Zr, TRC105
Address all correspondence to:
Dr. Weibo Cai
Departments of Radiology and Medical Physics
University of Wisconsin - Madison, Room 7137
1111 Highland Ave, Madison, WI 53705-2275, USA.
Tel: 608-262-1749; Fax: 608- 265-0614
E-mail: wcai@uwhealth.org
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