Sulfur [¹⁸F]Fluoride Exchange Click Chemistry Enabled Ultrafast Late-Stage Radiosynthesis

Area of Science:

• Radiochemistry
• Medicinal Chemistry
• Nuclear Medicine

Background:

• Efficient [18F]fluorination methods are crucial for developing novel positron emission tomography (PET) agents.
• The synthesis of target-specific organofluorine compounds for PET imaging remains a significant challenge.

Purpose of the Study:

• To develop an ultrafast isotopic exchange method for radiosynthesis of novel aryl [18F]fluorosulfate PET agents.
• To leverage sulfur fluoride exchange (SuFEx) click chemistry for rapid 18F-radiolabeling.

Main Methods:

• An ultrafast isotopic exchange reaction utilizing SuFEx click chemistry was employed.
• The method was applied to the automated 18F-radiolabeling of 25 diverse aryl fluorosulfates.
• Purification was achieved via simple cartridge filtration, avoiding HPLC.

Main Results:

• Excellent radiochemical yields (83-100%, median 98%) and high molar activity (280 GBq/µmol) were obtained at room temperature in 30 seconds.
• The method demonstrated broad applicability across 25 structurally diverse aryl fluorosulfates.
• Successful in vivo imaging of subcutaneous tumors was achieved using a PARP1-targeting agent.

Conclusions:

• The developed SuFEx-based radiosynthesis offers an efficient and rapid approach for generating novel aryl [18F]fluorosulfate PET agents.
• This method overcomes limitations in [18F]fluorination and facilitates the development of new diagnostic tools.
• The approach holds promise for in vivo molecular imaging, exemplified by PARP1-targeting studies.