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Positron emission tomography imaging of CD15 expression with 89Zr-Df-TRC15



Positron emission tomography imaging of CD15 expression with 89Zr-Df-TRC15







High tumor microvessel density correlates with a poor prognosis in multiple solid tumor types. The clinical gold standard for assessing microvessel density is CD15 immunohistochemistry on paraffin-embedded tumor specimens. The goal of this study was to develop an 89Zr-based PET tracer for noninvasive imaging of CD15 expression. TRC15, a chimeric anti-CD15 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 CD15 binding affinity of TRC15 and Df-TRC15. 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-TRC15. Another chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis of HUVECs revealed no difference in CD15 binding affinity between TRC15 and Df-TRC15, 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-TRC15 was 6.1? ?1.2, 14.3? ?1.2, 12.4? ?1.5, 7.1? ?.9, and 5.2? ?.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-TRC15. We report here the first successful PET imaging of CD15 expression with 89Zr as the radiolabel. Rapid, persistent, CD15-specific uptake of 89Zr-Df-TRC15 in the 4T1 tumor was observed.

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