Positron emission tomography imaging of CD105 expression with 89Zr-Df-TRC105

Research output: Contribution to journalJournal article – Annual report year: 2012Researchpeer-review

Without internal affiliation

  • Author: Hong, Hao

    University of Wisconsin-Madison, United States

  • Author: Severin, Gregory W.

    University of Wisconsin-Madison, Denmark

  • Author: Yang, Yunan

    University of Wisconsin-Madison, United States

  • Author: Engle, Jonathan W.

    University of Wisconsin-Madison, United States

  • Author: Zhang, Yin

    University of Wisconsin-Madison, United States

  • Author: Barnhart, Todd E.

    University of Wisconsin-Madison, United States

  • Author: Liu, Glenn

    University of Wisconsin-Madison, United States

  • Author: Leigh, Bryan R.

    TRACON Pharmaceuticals, Inc., United States

  • Author: Nickles, Robert J.

    University of Wisconsin-Madison, United States

  • Author: Cai, Weibo

    University of Wisconsin-Madison, United States

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Purpose: High tumor microvessel density correlates with a poor prognosis in multiple solid tumor types. The clinical gold standard for assessing microvessel density is CD105 immunohistochemistry on paraffin-embedded tumor specimens. The goal of this study was to develop an 89Zr-based PET tracer for noninvasive imaging of CD105 expression.
Methods: TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to p-isothiocyanatobenzyl- desferrioxamine (Df-Bz-NCS) and labeled with 89Zr. FACS analysis and microscopy studies were performed to compare the CD105 binding affinity of TRC105 and Df-TRC105. PET imaging, biodistribution, blocking, and ex-vivo histology studies were performed on 4T1 murine breast tumor-bearing mice to evaluate the pharmacokinetics and tumor-targeting of 89Zr-Df-TRC105. Another chimeric antibody, cetuximab, was used as an isotype-matched control.
Results: FACS analysis of HUVECs revealed no difference in CD105 binding affinity between TRC105 and Df- TRC105, which was further validated by fluorescence microscopy. 89Zr labeling was achieved with high yield and specific activity. Serial PET imaging revealed that the 4T1 tumor uptake of 89Zr-Df-TRC105 was 6.1±1.2, 14.3±1.2, 12.4±1.5, 7.1±0.9, and 5.2±0.3%ID/g at 5, 24, 48, 72, and 96 h after injection, respectively (n=4), higher than all organs starting from 24 h after injection, which provided excellent tumor contrast. Biodistribution data as measured by gamma counting were consistent with the PET findings. Blocking experiments, control studies with 89Zr-Df-cetuximab, and ex-vivo histology all confirmed the in vivo target specificity of 89Zr-Df- TRC105.
Conclusion: We report here the first successful PET imaging of CD105 expression with 89Zr as the radiolabel. Rapid, persistent, CD105-specific uptake of 89Zr-Df-TRC105 in the 4T1 tumor was observed. © Springer-Verlag 2011.
Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume39
Issue number1
Pages (from-to)138-148
Number of pages11
ISSN1619-7070
DOIs
Publication statusPublished - 2012
Externally publishedYes
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Radiology, Nuclear Medicine and Imaging, 89Zr, CD105/endoglin, Positron emission tomography (PET), RadioimmunoPET, TRC105, Tumor angiogenesis, antineoplastic agent, cetuximab, chimeric antibody, deferoxamine, endoglin, monoclonal antibody, tracer, trc 105, unclassified drug, zirconium, 4 isothiocyanatobenzyl desferrioxamine, 4-isothiocyanatobenzyl-desferrioxamine, cell surface receptor, diagnostic agent, drug derivative, ENG protein, human, isothiocyanic acid derivative, leukocyte antigen, radioisotope, animal cell, animal experiment, animal model, article, binding affinity, breast tumor, controlled study, drug specificity, ex vivo study, female, fluorescence activated cell sorting, fluorescence microscopy, histopathology, human, human cell, in vivo study, information processing, isotope labeling, mouse, non invasive procedure, nonhuman, positron emission tomography, protein binding, protein expression, umbilical vein endothelial cell, validation process, animal, chemistry, gene expression regulation, metabolism, methodology, tumor cell line, Animals, Antibodies, Monoclonal, Antigens, CD, Cell Line, Tumor, Deferoxamine, Female, Gene Expression Regulation, Neoplastic, Humans, Isothiocyanates, Mice, Positron-Emission Tomography, Radioisotopes, Receptors, Cell Surface, Zirconium, C6V6S92N3C Zirconium, J06Y7MXW4D Deferoxamine

ID: 104361681