Batch‐mode microfluidic radiosynthesis of N‐succinimidyl‐4‐[¹⁸F]fluorobenzoate for protein labelling

Abstract

aThe batch microfluidic technology is a promising system for sequential chemical steps combining the advantages of microscale reactions, while addressing some shortcomings of flow-through systems. We report herein the convenient three-step, one-pot synthesis and purification of These results illustrate how microfluidic batch devices are advantageous for producing radiotracers for molecular imaging, e.g. Positron emission tomography. The technology offers many benefits such as the possibility to use much smaller quantities of starting material, reduced reaction time combined with improved efficiency, and easier purification.

Micro-chemical synthesis of molecular probes on an electronic microfluidic device

“…It has previously been shown, with flow-through systems working with relatively large volumes (e.g., 0.5-1.0 mL), that changing from macroscale to microscale geometry leads to dramatic acceleration of reactions in the synthesis of ½ 18 FFDG (17, 18) and other PET tracers labeled with short-lived radioisotopes (19). Performing the chemistry in small volume batches in the 40 nL-60 μL range (6,20,21) offers further additional advantages, including: (i) reduced precursor consumption, (ii) accelerated heating and cooling due to reduced mass of liquid, and (iii) increased integration of overall synthesis processes (including [ 18 F]fluoride activation) onto the compact chip. It is possible to work at this scale due to the extremely minute mass of tracers needed for PET imaging (e.g., 6 pmol for typical human scan).…”

Microfluidic devices for radio chemical synthesis

“…The new device was rated for processing up to 500 mCi of 18 F, which is relevant to commercial production of radiotracers. 54 Similar improvements led to the construction of a device with only some of the components shielded. 14 …”

“…Combining this fi nding with higher fl uoride concentration, the authors developed a method yielding 64% of the target material in 25 min production. 54 An illustrative example was recently reported that directly compared a microfl uidic NanoTek apparatus, a microwave reactor, and a conventional module. 43 A group of authors from McMaster University, Canada, compared all three technologies in a model reaction of 99m Tc carbonyl complex with a popular 99m Tc chelate dithiazole valeric acid (Fig.…”

Emerging Technologies for Decentralized Production of PET Tracers

“…Despite several publications on these elastomeric chips, device reliability is limited by the inherent incompatibilities of the silicone rubber polymer with many solvents and reagents (Mukhopadhyay 2007 Elizarov et al 2011). A synthesis time of 25 min was achieved, which is substantially faster than that possible on macroscopic modules (60-100 min).…”