| AJNMMI Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |
Am J Nucl Med Mol Imaging 2012;2(1):1-13.
Original Article
Positron emission tomography and near-infrared fluorescence imaging of vascular
endothelial growth factor with dual-labeled bevacizumab
Yin Zhang, Hao Hong, Jonathan W. Engle, Yunan Yang, 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; University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Received November 30, 2011; accepted December 12, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab (Bev,
a humanized anti-VEGF monoclonal antibody) for first line treatment of cancer patients. The aim of this study was to develop a
dual-labeled Bev for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of VEGF. Bev was
conjugated to a NIRF dye (i.e. 800CW) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid
(p-SCN-Bn-NOTA) before 64Cu-labeling. Flow cytometry analysis of U87MG human glioblastoma cells revealed no difference in
VEGF binding affinity/specificity between Bev and NOTA-Bev-800CW. 64Cu-labeling of NOTA-Bev-800CW was achieved with high
yield. Serial PET imaging of U87MG tumor-bearing female nude mice revealed that tumor uptake of 64Cu-NOTA-Bev-800CW was 4.6
± 0.7, 16.3 ± 1.6, 18.1 ± 1.4 and 20.7 ± 3.7 %ID/g at 4, 24, 48 and 72 h post-injection respectively (n = 4), corroborated by in vivo/ex
vivo NIRF imaging and biodistribution studies. Tumor uptake as measured by ex vivo NIRF imaging had a good linear correlation
with the %ID/g values obtained from PET (R2 = 0.93). Blocking experiments and histology both confirmed the VEGF specificity of
64Cu-NOTA-Bev-800CW. The persistent, prominent, and VEGF-specific uptake of 64Cu-NOTA-Bev-800CW in the tumor, observed by
both PET and NIRF imaging, warrants further investigation and future clinical translation of such Bev-based imaging agents.
(ajnmmi1111004).
Keywords: Positron emission tomography (PET), Near-infrared fluorescence (NIRF) Imaging, Vascular endothelial growth factor
(VEGF), 64Cu, Tumor angiogenesis, Cancer
Full text PDF
Address all correspondence to:
Weibo Cai, PhD
Departments of Radiology and Medical Physics
University of Wisconsin - Madison
Room 7137, 1111 Highland Ave
Madison, WI 53705-2275, USA.
Phone: 608-262-1749; Fax: 608- 265-0614
Email: wcai@uwhealth.org
Original Article
Positron emission tomography and near-infrared fluorescence imaging of vascular
endothelial growth factor with dual-labeled bevacizumab
Yin Zhang, Hao Hong, Jonathan W. Engle, Yunan Yang, 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; University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Received November 30, 2011; accepted December 12, 2011; Epub December 15, 2011; Published January 1, 2012
Abstract: The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval of bevacizumab (Bev,
a humanized anti-VEGF monoclonal antibody) for first line treatment of cancer patients. The aim of this study was to develop a
dual-labeled Bev for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of VEGF. Bev was
conjugated to a NIRF dye (i.e. 800CW) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid
(p-SCN-Bn-NOTA) before 64Cu-labeling. Flow cytometry analysis of U87MG human glioblastoma cells revealed no difference in
VEGF binding affinity/specificity between Bev and NOTA-Bev-800CW. 64Cu-labeling of NOTA-Bev-800CW was achieved with high
yield. Serial PET imaging of U87MG tumor-bearing female nude mice revealed that tumor uptake of 64Cu-NOTA-Bev-800CW was 4.6
± 0.7, 16.3 ± 1.6, 18.1 ± 1.4 and 20.7 ± 3.7 %ID/g at 4, 24, 48 and 72 h post-injection respectively (n = 4), corroborated by in vivo/ex
vivo NIRF imaging and biodistribution studies. Tumor uptake as measured by ex vivo NIRF imaging had a good linear correlation
with the %ID/g values obtained from PET (R2 = 0.93). Blocking experiments and histology both confirmed the VEGF specificity of
64Cu-NOTA-Bev-800CW. The persistent, prominent, and VEGF-specific uptake of 64Cu-NOTA-Bev-800CW in the tumor, observed by
both PET and NIRF imaging, warrants further investigation and future clinical translation of such Bev-based imaging agents.
(ajnmmi1111004).
Keywords: Positron emission tomography (PET), Near-infrared fluorescence (NIRF) Imaging, Vascular endothelial growth factor
(VEGF), 64Cu, Tumor angiogenesis, Cancer
Full text PDF
Address all correspondence to:
Weibo Cai, PhD
Departments of Radiology and Medical Physics
University of Wisconsin - Madison
Room 7137, 1111 Highland Ave
Madison, WI 53705-2275, USA.
Phone: 608-262-1749; Fax: 608- 265-0614
Email: wcai@uwhealth.org
 |  |  |  |  |  |  |