"In-loop" [¹¹ C]CO₂ fixation: Prototype and proof of concept

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Organic Synthesis

Background:

• Carbon-11 labeled carbon dioxide ([11C]CO2) is a crucial precursor for synthesizing positron emission tomography (PET) radiotracers.
• Direct [11C]CO2 fixation offers a streamlined approach for incorporating the 11C label into various molecular structures.

Purpose of the Study:

• To develop and validate an "in-loop" apparatus for robust and reproducible synthesis of [11C]carbonyl-based radiotracers.
• To demonstrate the utility of the developed method for producing clinically relevant PET imaging agents.

Main Methods:

• Development of an "in-loop" apparatus utilizing [11C]CO2 fixation technology.
• Synthesis of model compounds including carbamates, symmetrical and unsymmetrical ureas.
• Application of the method for synthesizing a monoamine oxidase B inhibitor ([11C]SL25.1188) and novel fatty acid amide hydrolase inhibitors.

Main Results:

• The "in-loop" [11C]CO2 fixation method is simple, efficient, and operates at ambient conditions.
• Successful synthesis of various [11C]carbonyl-labeled compounds, including carbamates and ureas.
• High yields and purity (>99%) of radiotracers were achieved, with molar radioactivity ≥80 GBq/μmol.

Conclusions:

• The developed "in-loop" apparatus provides a reliable and efficient platform for the synthesis of [11C]carbonyl radiotracers.
• This method facilitates the production of diverse PET imaging agents, including novel inhibitors and established tracers.
• The synthesized radiotracers demonstrate high quality suitable for clinical applications in PET imaging.