Abstract
Microfluidic synthesis techniques can offer improvement over batch syntheses which are currently used for radiopharmaceutical production. These improvements are, for example, better mixing of reactants, more efficient energy transfer, less radiolysis, faster reaction optimization, and overall improved reaction control. However, scale-up challenges hinder the routine clinical use, so the main advantage is currently the ability to optimize reactions rapidly and with low reactant consumption. Translating those results to clinical systems could be done based on calculations, if kinetic constants and diffusion coefficients were known. This study describes a microfluidic system with which it was possible to determine the kinetic association rate constants for the formation of [177Lu]Lu-DOTA-TATE under conditions currently used for clinical production. The kinetic rate constants showed a temperature dependence that followed the Arrhenius equation, allowing the determination of Arrhenius parameters for a Lu-DOTA conjugate (A = 1.24 ± 0.05 × 1019 M-1 s-1, EA = 109.5 ± 0.1 × 103 J mol-1) for the first time. The required reaction time for the formation of [177Lu]Lu-DOTA-TATE (99% yield) at 80 °C was 44 s in a microfluidic channel (100 μm). Simulations done with COMSOL Multiphysics® indicated that processing clinical amounts (3 mL reaction solution) in less than 12 min is possible in a micro- or milli-fluidic system, if the diameter of the reaction channel is increased to over 500 μm. These results show that a continuous, microfluidic system can become a viable alternative to the conventional, batch-wise radiolabelling technique.
Highlights
Recent years have seen increasing interest in the application of microfluidics for the synthesis of radiopharmaceuticals
This study describes a microfluidic system with which it was possible to determine the kinetic association rate constants for the formation of [177Lu]Lu-DOTA-TATE under conditions currently used for clinical production
Due to optimal heat and mass transfer in the microfluidic system much lower reaction times (44 s at 80 °C for 99% yield) are needed than those reported for conventional systems (8–15 min at pH 4 and 80 °C).[25]
Summary
Recent years have seen increasing interest in the application of microfluidics for the synthesis of radiopharmaceuticals. This development started in the early 2000s with 18F or 11C containing compounds,[1] but studies published in the last few years showed the advantage of microfluidics over conventional methods for metal containing radiopharmaceuticals.[2,3,4,5,6,7] The reason for the success of microfluidics is that downsizing reaction vessels to the micro-scale allows for better mixing of reactants, more efficient energy transfer, less radiolysis, faster reaction optimization, and overall improved reaction control.[1,2,3,4,5,6,7,8] limited throughput of microfluidic devices and the difficult interface between batch and continuous-flow processes used for different radiopharmaceutical preparation steps still hinder the routine clinical use.[9] Up to now, the clear. The determined constants could be used to optimize the design of reaction vessels using computational fluid dynamics, as Haroun et al showed recently for the microfluidic synthesis of [11C]raclopride.[10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
