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Bioconjug Chem. 2016 May 18;27(5):1390-1399. doi: 10.1021/acs.bioconjchem.6b00164. Epub 2016 Apr 27.

New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule Generation from the Solid Phase.

Author information

1
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, United States.
2
Molecular Imaging Innovations Institute (MI3), Department of Radiology, Weill Cornell Medicine, New York, New York 10065, United States.
3
Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States.
4
Howard Hughes Medical Institute, La Jolla, California 92093, United States.
#
Contributed equally

Abstract

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 [(18)F]-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 [(18)F]-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.

PMID:
27064381
PMCID:
PMC4916912
DOI:
10.1021/acs.bioconjchem.6b00164
[Indexed for MEDLINE]
Free PMC Article

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