Paper EM+SS+TF-ThA9
On-chip [¹⁸F]fluoride Concentration for Microfluidic PET Tracer Synthesis

Thursday, November 10, 2016, 5:00 pm, Room 102A

Positron emission tomography (PET) is a valuable medical imaging method that relies on radioactive tracers that target specific sites in the body. Development of these tracers is currently hindered by the enormous infrastructure requirements to perform the necessary radioisotope production and subsequent reactions. To overcome this hurdle and facilitate PET tracer development, we are designing simple, modular microfluidic systems that support on-chip radiosynthesis reactions with small volumes of reagents. In this work, [¹⁸F]fluoride (a positron emitter widely used in PET imaging due to its convenient half-life of 110 minutes) is concentrated with a miniaturized anion exchange column located in a microfluidic device fabricated in polydimethylsiloxane (PDMS). By employing a microfluidic device, we aim to achieve more controlled diffusion and reactive kinetics. Instead of relying on complicated flow control elements (e.g. valves), in this microfluidic system, a channel containing pillars with a spacing less than the average diameter of the anion exchange beads is used to trap relatively monodispersed, rigid polystyrene/divinyl benzene beads. We characterized the ability of this miniaturized on-chip exchange column to capture and release quantities of [¹⁸F]fluoride appropriate for human imaging (a typical dose is 10 mCi).

Our device is composed of a main chamber with larger microchannels (9 mm long) connected to an inlet and outlet. A laser writer (Heidelberg µPG 101) was used to create patterns on a silicon wafer using a 60 µm thick layerof mr-DWL resist; this template was subsequently used to pattern a microfluidic structure in PDMS. The desired quantity (2.9 mL) of anion exchange beads was trapped by a double row of square pillars near the outlet of the chamber, and the beads subsequently activated with 1.0 M of KHCO₃. Diluted [¹⁸F]fluoride (100 mCi/mL) sourced from a nearby cyclotron was introduced into the system using a syringe pump, flowing at 0.05 mL/min for 10 minutes.

By quantifying the radioactivity of the [¹⁸F]fluoride introduced, the radioactivity of the chip, and the radioactivity of the outflow, we could determine trapping and release efficiency. We observed near complete capture of [¹⁸F]fluoride (50 mCi)on our chips in a relatively short time. Moreover, elution with a small volume (less than 200 mL) of Kryptofix (K₂₂₂)/K₂CO₃ was able to release nearly all the [¹⁸F]fluoride (49 mCi). Thus, this device is capable of simply and efficiently trapping [¹⁸F]fluoride and controllably releasing the concentrated radiolabel in small volumes for downstream reaction with desired molecules.