Recent Advances in Microfluidic Devices for the Radiosynthesis of PET‐imaging Probes

Abstract

In order to accommodate the growing demand for positron emission tomography (PET), it will be necessary to create innovative radiochemical and engineering technologies to optimize the manufacture and development of PET probes. Microfluidic devices allow radiosynthesis to be performed in microscale amounts, significantly impacting PET tracer production. Compared to traditional methods, microfluidic devices can produce PET tracers in a shorter time, higher yields, with lower reagent consumption, higher molar activity, and faster purification. This review examines microfluidic devices from an engineering perspective. Recently developed microfluidic radiosynthesis devices are classified into three categories according to their reaction volume: continuous-flow, batch-flow, and droplet-based microreactors. The principles of device architecture, radiosynthesis process, and the relative strengths and limitations of each category are emphasized by citing typical examples. Finally, the possible future applications of this technology are outlined. A flexible, miniature, fully automated radiochemical microfluidic platform will offer more straightforward and cheaper molecular imaging procedures and the potential for precision medicine that could allow operators to create customized tracers for individual patient doses.

Microfluidic synthesis of radiotracers: recent developments and commercialization prospects

“…Finally, the radiotracer must be purified to produce a usable dose; this is most often accomplished via either HPLC or SPE using another packed bed. 22,23 The exact design of each synthesis module varies, but, importantly, they all contain the necessary unit operations to execute a complete synthesis.…”

“…However, consideration and integration of all components has become more common as the field rapidly progresses towards commercialization. In this review, research projects have been divided by their reactor methodology into 1) continuous flow 2) batch and 3) droplet 22,29 approaches.…”

Synthesis of [68Ga]Ga-PSMA-11 using the iMiDEV™ microfluidic platform

“…Recently, different microfluidic devices have been developed to set up this new way of producing radiopharmaceuticals. 15,16 Only a few examples of 68 Galabelling using microfluidic technology have been reported so far. The microfluidic synthesizer Advion NanoTek uses a liquid flow reaction unit.…”

Proof-of-concept optimization of a copper-mediated 18F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

“…24 Microfluidic devices have emerged as efficient, compact, and cost-effective platforms with great potential for diverse radiotracer production, leading to the development of various microfluidic tools in radiochemistry over the past 15 years. [25][26][27][28][29] These systems can be roughly divided into two categories: flow chemistry systems and microscale batch systems. Flow-based reactors have shown great effectiveness in synthesizing various radiopharmaceuticals, 30 but these setups rely on macroscale components for some synthesis steps (e.g., radioisotope concentration and product purification), making them similar to conventional radiosynthesizers in terms of size, shielding requirements, and operating volumes.…”