Novel Method for Radiolabeling and Dimerizing Thiolated Peptides Using (18)F-Hexafluorobenzene.

Area of Science:

• Radiochemistry
• Organic Chemistry
• Molecular Imaging

Background:

• Hexafluorobenzene (HFB) offers unique reactivity with thiols for perfluoroaromatic linkage.
• Integrin αvβ3 receptors are crucial targets for cancer imaging due to their overexpression in tumors.

Purpose of the Study:

• To modify the HFB-thiol reaction for synthesizing dimeric (18)F-RGD-tetrafluorobenzene (TFB)-RGD.
• To develop an automated radiofluorination process for efficient production of (18)F-HFB.
• To evaluate the targeted imaging capabilities of the novel radioligand.

Main Methods:

• Preparation of (18)F-HFB via a fluorine exchange reaction at room temperature.
• Optimization of automated radiofluorination to maximize specific activity.
• Reaction of (18)F-HFB with thiolated c(RGDfk) peptide under basic and reducing conditions.

Main Results:

• Successful synthesis of dimeric (18)F-RGD-TFB-RGD.
• Demonstrated integrin receptor-specific binding and cellular uptake.
• Observed in vivo tumor accumulation of the (18)F-labeled RGD peptide.

Conclusions:

• (18)F-HFB can be efficiently incorporated into thiol-containing peptides at room temperature.
• This method provides a novel route for developing targeted molecular imaging agents.
• (18)F-RGD-TFB-RGD shows promise for non-invasive imaging of integrin αvβ3 expression in tumors.