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

Research output: Contribution to journalJournal articleResearchpeer-review

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 pisothiocyanatobenzyl- 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.
Original languageEnglish
JournalAmerican Journal of Translational Research
Volume4
Issue number3
Pages (from-to)333-346
Number of pages14
ISSN1943-8141
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Medicine (all)
  • Cancer Research
  • Clinical Biochemistry
  • Molecular Medicine
  • 89Zr
  • CD105/endoglin
  • Near-infrared fluorescence (NIRF)
  • Positron emission tomography (PET)
  • TRC105
  • Tumor angiogenesis
  • 4 isothiocyanatobenzyl desferrioxamine cetuximab 800cw zr 89 conjugate
  • 4 isothiocyanatobenzyl desferrioxamine trc105 800cw zr 89 conjugate
  • cetuximab
  • endoglin
  • monoclonal antibody
  • monoclonal antibody TRC105
  • tracer
  • unclassified drug
  • angiogenesis
  • animal cell
  • animal experiment
  • animal model
  • animal tissue
  • antigen expression
  • article
  • binding affinity
  • breast cancer
  • cancer model
  • conjugation
  • controlled study
  • drug distribution
  • drug protein binding
  • drug tumor level
  • ex vivo study
  • female
  • fluorescence activated cell sorting
  • fluorescence imaging
  • human
  • human cell
  • in vivo study
  • medical device
  • mouse
  • near infrared fluorescence imaging
  • nonhuman
  • positron emission tomography
  • prognosis
  • radioactivity
  • solid tumor

Cite this

Zhang, Y., Hong, H., Severin, G. W., Engle, J. W., Yang, Y., Goel, S., Nathanson, A. J., Liu, G., Nickles, R. J., Leigh, B. R., Barnhart, T. E., & Cai, W. (2012). ImmunoPET and near-infrared fluorescence imaging of CD105 expression using a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. American Journal of Translational Research, 4(3), 333-346.