Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW

Hao Hong, Yin Zhang, Gregory W. Severin, Yunan Yang, Jonathan W. Engle, Gang Niu, Robert J. Nickles, Xiaoyuan Chen, Bryan R. Leigh, Todd E. Barnhart, Weibo Cai

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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 89Zr to yield 89Zr-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 89Zr-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 89Zr-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. © 2012 American Chemical Society.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume9
Issue number8
Pages (from-to)2339-2349
Number of pages11
ISSN1543-8384
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery
  • 89Zr
  • breast cancer
  • CD105 (endoglin)
  • lung metastasis
  • near-infrared fluorescence (NIRF)
  • positron emission tomography (PET)
  • tumor angiogenesis
  • cetuximab
  • deferoxamine
  • deferoxamine cetuximab IRDye 800CW zr 89
  • deferoxamine monoclonal antibody TRC 105 IRDye 800CW zr 89
  • endoglin
  • monoclonal antibody
  • tracer
  • trc 105
  • unclassified drug
  • zirconium
  • zirconium 89
  • animal cell
  • animal experiment
  • animal model
  • animal tissue
  • article
  • bioluminescence
  • controlled study
  • drug distribution
  • drug synthesis
  • drug uptake
  • female
  • human
  • human cell
  • mouse
  • near infrared fluorescence
  • nonhuman
  • positron emission tomography
  • priority journal
  • radiation dose
  • tumor volume

Cite this

Hong, H., Zhang, Y., Severin, G. W., Yang, Y., Engle, J. W., Niu, G., Nickles, R. J., Chen, X., Leigh, B. R., Barnhart, T. E., & Cai, W. (2012). Multimodality imaging of breast cancer experimental lung metastasis with bioluminescence and a monoclonal antibody dual-labeled with 89Zr and IRDye 800CW. Molecular Pharmaceutics, 9(8), 2339-2349. https://doi.org/10.1021/mp300277f