title: 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.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Severin
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.forename: Shreya
authors.initials: S
authors.lastname: Goel
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Nathanson
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Leigh
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai