Advantages of Radiochemistry in Microliter Volumes

Abstract

Positron emission tomography (PET) provides quantitative 3D visuali-zation of physiological parameters (e.g., metabolic rate, receptor density, gene expression, blood flow) in real time in the living body. By enabling measurement of differences in such characteristics between normal and diseased tissues, PET serves as vital tool for basic research as well as for clinical diagnosis and patient management. Prior to a PET scan, the patient is injected with a short-lived tracer labeled with a positron-emitting isotope. Safe preparation of the tracer is an expensive process, requiring specially trained personnel and high-cost equipment operated within hot cells. The current centralized manufacturing strategy, in which large batches are prepared and divided among many patients, enables the most commonly used tracer (i.e., [ 18 F]FDG) to be obtained at an affordable price. However, as the diversity of tracers increases, other strategies for cost reduction will become necessary. This challenge is being addressed by the development of miniaturized radiochemistry instrumentation based on microfluidics. These com-pact systems have the potential to significantly reduce equipment cost and shielding while increasing diversity of tracers produced in a given facility. The most common approach uses " flow-through " microreactors, which leverage the ability to precisely control reaction conditions to improve synthesis times and yields. Several groups have also developed " batch " microreactors which offer significant additional advantages such as reduced reagent consumption, simpler purifications, and excep-tionally high specific activity, by reducing operating volumes by orders of magni-tude. In this chapter, we review these " batch " approaches and the advantages of using small volumes, with special emphasis on digital microfluidics, in which reactions have been performed with volumes as low as ~1 μL. Keywords Microfluidics • Radiosynthesis • Positron emission tomography (PET) • Electrowetting-on-dielectric (EWOD) • Microscale chemistry P.Y. Keng • M. Sergeev • R.M. van Dam (*)