Journal article
Positron emission tomography imaging of CD105 expression with 89Zr-Df-TRC105
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 (89)Zr-based PET tracer for noninvasive imaging of CD105 expression.
TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) and labeled with (89)Zr. 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 (89)Zr-Df-TRC105.
Another chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis of HUVECs revealed no difference in CD105 binding affinity between TRC105 and Df-TRC105, which was further validated by fluorescence microscopy. (89)Zr labeling was achieved with high yield and specific activity.
Serial PET imaging revealed that the 4T1 tumor uptake of (89)Zr-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 (89)Zr-Df-cetuximab, and ex-vivo histology all confirmed the in vivo target specificity of (89)Zr-Df-TRC105. We report here the first successful PET imaging of CD105 expression with (89)Zr as the radiolabel.
Rapid, persistent, CD105-specific uptake of (89)Zr-Df-TRC105 in the 4T1 tumor was observed.
Language: | English |
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Publisher: | Springer-Verlag |
Year: | 2012 |
Pages: | 138-148 |
ISSN: | 16197089 and 16197070 |
Types: | Journal article |
DOI: | 10.1007/s00259-011-1930-x |
4-isothiocyanatobenzyl-desferrioxamine 89Zr Animals Antibodies, Monoclonal Antigens, CD CD105/Endoglin CD105/endoglin Cardiology Cell Line, Tumor Deferoxamine ENG protein, human Endoglin Female Gene Expression Regulation, Neoplastic Humans Imaging / Radiology Isothiocyanates Medicine & Public Health Mice Nuclear Medicine Oncology Orthopedics Positron emission tomography (PET) Positron-Emission Tomography RadioimmunoPET Radioisotopes Receptors, Cell Surface TRC105 Tumor angiogenesis Zirconium