New Dioxaborolane Chemistry Enables [(18)F]-Positron-Emitting, Fluorescent [(18)F]-Multimodality Biomolecule...

Area of Science:

• Bioconjugation Chemistry
• Medical Imaging
• Radiochemistry

Background:

• Developing efficient methods for producing radiolabeled imaging probes is crucial for advancing diagnostic capabilities.
• Existing methods for attaching biomolecules to imaging agents can be complex and may affect biomolecule function.
• Multimodality imaging offers enhanced diagnostic accuracy by combining information from different imaging techniques.

Purpose of the Study:

• To develop a simplified and efficient method for producing radiolabeled antibodies for positron emission tomography (PET) and near-infrared fluorescent (NIRF) multimodality imaging.
• To demonstrate the utility of this new chemistry in labeling antibodies for specific cancer types.

Main Methods:

• A novel dioxaborolane protecting group chemistry was employed for antibody immobilization on a solid support.
• Temperature and organic solvent-sensitive biomolecules were covalently attached to a biotin-bearing dioxaborolane.
• Aqueous fluoride treatment released the labeled antibody, creating [(18)F]-trifluoroborate-antibody conjugates.
• The method was applied to anti-epithelial cell adhesion molecule (EpCAM) and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs).

Main Results:

• The new chemistry simplifies probe production and allows for bioorthogonal labeling without inhibiting antigen binding.
• [(18)F]-specific activity was increased compared to solution-based radiosyntheses.
• Successful dual modality PET/NIRF imaging of prostate and lung adenocarcinoma tumors was achieved using labeled anti-EpCAM and Cetuximab antibodies, respectively.
• Colocalized, tumor-specific signals confirmed the imaging utility.

Conclusions:

• The developed dioxaborolane-fluoride reaction provides a robust and versatile platform for producing dual modality imaging probes.
• This chemistry facilitates the labeling of various biomolecules, including antibodies, nanoparticles, and small molecules, for diverse disease imaging applications.
• The technology holds significant potential for improving diagnostic accuracy and enabling personalized medicine through advanced imaging.