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Am J Transl Res. 2012;4(3):333-46. Epub 2012 Jul 27.

ImmunoPET and near-infrared fluorescence imaging of CD105 expression using a monoclonal antibody dual-labeled with (89)Zr and IRDye 800CW.

Abstract

CD105 (endoglin) is an independent marker for poor prognosis in more than 10 solid tumor types. The goal of this study was to develop a CD105-specific agent for both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging, which has potential clinical applications in the diagnosis and imaged-guided resection of solid tumors. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to a NIRF dye (800CW) and p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS) before (89)Zr-labeling. Another chimeric antibody, cetuximab, was used as an isotype-matched control. FACS analysis revealed no difference in CD105 binding affinity/specificity between TRC105 and Df-TRC105-800CW. Serial PET imaging revealed that the 4T1 tumor uptake of (89)Zr-Df-TRC105-800CW was 6.3 ± 1.9, 12.3 ± 1.3, and 11.4 ± 1.1 %ID/g at 4, 24, and 48 h post-injection (p.i.) respectively (n = 3), higher than all organs starting from 24 h p.i., which provided excellent tumor contrast. Tumor uptake as measured by both in vivo and ex vivo NIRF imaging had a linear correlation with the %ID/g values obtained from PET, corroborated by biodistribution studies. Blocking experiments, control studies with (89)Zr-Df-cetuximab-800CW, and histology all confirmed the CD105 specificity of (89)Zr-Df-TRC105-800CW. In conclusion, herein we report dual-modality PET and NIRF imaging of CD105 expression in a breast cancer model, where CD105-specific uptake of (89)Zr-Df-TRC105-800CW in the tumor was observed.

KEYWORDS:

89Zr; CD105/endoglin; TRC105; near-infrared fluorescence (NIRF); positron emission tomography (PET); tumor angiogenesis

PMID:
22937210
PMCID:
PMC3426387
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