Positron emission tomography (PET) is a molecular diagnostic imaging technology to quantitatively visualize biological processes in vivo. For many applications, including imaging of low-tissue density targets (e.g., neuroreceptors), imaging in small animals, and evaluation of novel tracers, the injected PET tracer must be produced with high molar activity to ensure low occupancy of biological targets and avoid pharmacologic effects. Additionally, high molar activity is essential for tracers with lengthy syntheses or tracers transported to distant imaging sites. Here we show that radiosynthesis of PET tracers in microliter volumes instead of conventional milliliter volumes results in substantially increased molar activity, and we identify the most relevant variables affecting this parameter. Furthermore, using the PET tracer [ 18 F]fallypride, we illustrate that molar activity can have a significant impact on biodistribution. With full automation, microdroplet platforms could provide a means for radiochemists to routinely, conveniently, and safely produce PET tracers with high molar activity.

[18F]fallypride was synthesized in a batch microfluidic chip with a radiochemical yield of 65±6% (n=7) and an average specific activity of 730 GBq/μmol (20 Ci/μmol) (n=4). Specific activity was ~2-fold higher than [18F]fallypride synthesized on a macroscale radiosynthesizer, despite starting with significantly less radioactivity, and thus safer conditions, in the microchip.

Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [18F]fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this report, we demonstrate the possibility of 18F-radiofluorination in highly aqueous media. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile-thexyl alcohol solvent mixture and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [18F]fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved. The substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic and cycloaliphatic tosylated precursors.