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

  • Hao Hong
  • Gregory W. Severin
  • Yunan Yang
  • Jonathan W. Engle
  • Yin Zhang
  • Todd E. Barnhart
  • Glenn Liu
  • Bryan R. Leigh
  • Robert J. Nickles
  • Weibo Cai
Original Article

Abstract

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.

Keywords

CD105/endoglin Positron emission tomography (PET) Tumor angiogenesis 89Zr RadioimmunoPET TRC105 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hao Hong
    • 1
  • Gregory W. Severin
    • 2
  • Yunan Yang
    • 1
  • Jonathan W. Engle
    • 2
  • Yin Zhang
    • 2
  • Todd E. Barnhart
    • 2
  • Glenn Liu
    • 3
    • 4
  • Bryan R. Leigh
    • 5
  • Robert J. Nickles
    • 2
  • Weibo Cai
    • 1
    • 2
    • 4
  1. 1.Department of RadiologyUniversity of Wisconsin - MadisonMadisonUSA
  2. 2.Department of Medical PhysicsUniversity of Wisconsin - MadisonMadisonUSA
  3. 3.Department of MedicineUniversity of Wisconsin - MadisonMadisonUSA
  4. 4.University of Wisconsin Carbone Cancer CenterMadisonUSA
  5. 5.TRACON Pharmaceuticals, IncSan DiegoUSA

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