The use of continuous-flow microfluidics has shown tremendous advantages in the area of radiosynthesis of imaging agents for both pre-clinical and our recent work has advanced the first clinical research studies with PET radiopharmaceuticals enabled by this technology . In this paper we will present a number of advances that have occurred in the field as follows:1) Specific 18F-labeling reactions where flow chemistry is superior to conventional vessel based radiosynthesis. These are best exemplified when the precursor or product is unstable under the reaction conditions.2) Improved purification methods: A common problem with the use semipreparative HPLC for the preparation of pre-clinical doses is the low radioactive concentration that results from the large volume of mobile phase in the isolated peak, which must be further concentrated and formulated prior to injection. We will present a system which allows for the interfacing of a commercial microfluidic system (Advion NanoTek) and conventional synthesis box (GE Tracerlab FXFN) to a newly designed analytical HPLC column purification system which results in 5- to 15-fold increases in the radioactive concentration and a significant reduction in the starting activity required.3) Use of hydrogenation reactions: These reactions have proven to be labor intensive and time consuming and as such have not been utilized to their full potential in radiotracer synthesis. Here we will show the utility of the combination of the two microfluidic flow systems, namely the NanoTek and a flow hydrogenation system (H-Cube; ThalesNano, Inc), with the HPLC purification and formulation benefits of the commonly used GE Tracerlab FXFN radiosynthesizer or our new analytical column purification system, into one seamless operation.4) First in human imaging study with a PET radiopharmaceutical prepared by microfluidic flow chemistry: The validation of multiple PET radiopharmaceuticals and first in human imaging study enabled by this technique will be presented.

Flow microfluidics for PET: Bench to bedside realized

248th National Meeting (2014)

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