Microfluidic Polymer Monoliths for Micro-Scale Preparation of PET Probes

Summary

Background

Fluorine-18 (18F-) is an important isotope in radiotracer synthesis for positron emission tomography (PET). Fluorine-18 possesses many desirable properties such as a strong and stable C-F bond, relatively low energy, and a half-life that provides sufficient time for local shipping. Radiosynthesis of the majority of PET probes involves the concentration of the F18­fluoride ion, followed by several cycles of azeotropic distillation to remove all the water. The dried and activated 18F is then transferred to the microfluidic or capillary microreactor for subsequent fluorination steps. These steps have traditionally mandated a scale of production that is much greater than the required amount of isotope, leading to severe limitations in cost, speed of production and reaction efficiency. The inefficient production of the radioisotope is a restriction on further research and clinical study of new radiolabeled compounds. Novel approaches that can efficiently downscale the preparation and synthesis of PET probes have enormous potential in improving research and access to PET imaging.   

Innovation

Dr. Keng and colleagues in UCLA’s Department of Molecular & Medical Pharmacology have developed a system that uses functional polymer monoliths on a flow-through microfluidic platform to perform ion concentration, solvent exchange and activation processes within a single chip with high efficiency. The polymer monolith dually concentrates and activates the [18F] fluoride ion on the microfluidic chip thereby circumventing additional drying steps. The unique polymer monolith is highly suitable for microfluidic applications due to the ease of preparation, high loading capacity, high surface area, tunable pore size, tunable functionalities and high hydrodynamic flow. The researchers have confirmed that the anion exchange monoliths polymerized within the 13 μL serpentine channels of microfluidic chip consisted sufficient surface area to trap [18F]fluoride ion up to 1 Ci in radioactivity. Additionally, they have successfully prepared and demonstrate the fluoride trapping and activation in other micro-volume chambers. The Keng group has successfully demonstrated comparable fluorination efficiencies of several commonly used PET probe intermediates. Thus, this method and apparatus provides a practical and efficient interface for concentrating, drying, and activation non-carrier added 18F-fluoride directly from the cyclotron into the tens to hundreds of microliters volume. This technology platform can also be adapted for conventional macroscale radiosynthesizer to eliminate the time consuming drying processes.  

Applications

• Research and development of PET probe synthesis: The technology can be used for customizable synthesis of PET probes.
• The present invention could be applicable to any flow through microfluidic devices in any field such as radiosynthesis, chemical syntheses, and concentration of ions for environmental analyses, and sample preparation, such as concentrating minute amount of analyte to improve the downstream detection. 
• The present invention can also be easily adapted to any conventional macroscale radiosynthesizer by replacing the anion exchange cartridge used for [18F]fluoride concentration.

Advantages

• The technology performs ion concentration, solvent exchange and activation processes within a single chip with high efficiency. 
• No size limitation: the technology provides a means to circumvent the difficulty of packing micron­sized beads onto microfluidic channels. 
• The technology improves efficiency by reducing radioactivity losses due to surface adsorption to the walls of traditional reaction vessels.
• Polymer monolith is uniquely suitable for microfluidic application due to:

o Ease of preparation
o High loading capacity
o High surface area
o Tunable pore size
o Tunable functionalities

o High hydrodynamic flow

State Of Development

Related Materials

• Solid phase [18F]fluorination on a Flow-through Glass Microfluidic Chip. Intl Conf in Miniaturized Systems for Chemistry and Life Sciences. (2012)
• ABSTRACT: Functional polymer monoliths towards solid phase radiosynthesis on microfluidic chip. J Nucl Med. (2012(
• ABSTRACT: Recyclable quaternary ammonium functionalized polymer monoliths for efficient on-chip fluoride pre-concentration. J Nucl Med. (2012)

Patent Status