期刊
BIOCONJUGATE CHEMISTRY
卷 27, 期 5, 页码 1390-1399出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.6b00164
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资金
- National Institute of General Medical Sciences Postdoctoral Fellowship [F32GM089114]
- US National Institutes of Health [CA158448]
- Howard Hughes Medical Institute
- National Institute of Biomedical Imaging and Bioengineering [K99/R00 (EB013904)]
New protecting group chemistry is used to greatly simplify imaging probe production. Temperature and organic solvent-sensitive biomolecules are covalently attached to a biotin bearing dioxaborolane, which facilitates antibody immobilization on a streptavidin-agarose solid-phase support. Treatment with aqueous fluoride triggers fluoride-labeled antibody release from the solid phase, separated from unlabeled antibody, and creates [F-18]-trifluoroborate-antibody for positron emission tomography and near-infrared fluorescent (PET/NIRF) multimodality imaging. This dioxaborolane-fluoride reaction is bioorthogonal, does not inhibit antigen binding, and increases [F-18]-specific activity relative to solution-based radiosyntheses. Two applications are investigated: an anti-epithelial cell adhesion molecule (EpCAM) monoclonal antibody (mAb) that labels prostate tumors and Cetuximab, an anti-epidermal growth factor receptor (EGFR) mAb (FDA approved) that labels lung adenocarcinoma tumors. Colocalized, tumor-specific NIRF and PET imaging confirm utility of the new technology. The described chemistry should allow labeling of many commercial systems, diabodies, nanoparticles, and small molecules for dual modality imaging of many diseases.
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