Measurement of reaction kinetics of [¹⁷⁷Lu]Lu-DOTA-TATE using a microfluidic system

Abstract

a 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 [ 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.

Chemical Kinetics of Radiolabelling Reactions

“…In the examples highlighted, minimising the precursor concentration during radiosynthesis of [ 68 Ga]GaPSMA‐11 and [ 89 Zr]Zr‐DFO‐J591 has the effect of driving these reactions into second‐order kinetic schemes. As a further example, Oehlke and co‐workers reported elegant studies in which a microfluidic device was used to measure the reaction kinetics of [ 177 Lu]Lu‐DOTA‐TATE radiosynthesis . Their experiments found that under the conditions employed, [ 177 Lu]Lu‐DOTA‐TATE radiosynthesis obeyed second‐order kinetics with the measured rate constant k 2 of 60.4±2.8 m −1 s −1 at 59.5±0.2 °C and increasing to 1868±100 m −1 s −1 at 88.5±0.2 °C.…”

3D-printed automation for optimized PET radiochemistry

“…Continuous flow processes have been used to reduce reaction times and reagent amounts in a variety of organic and bio-organic reactions ( 32 ). Recently, microfluidic continuous flow approaches have also been applied to radiochemical synthesis ( 33 , 34 ).…”

High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress

“…[9][10][11] Using custom built and commercial flow systems, a wide range of different PET and SPECT tracers have been synthesized, including molecules labeled with fluorine-18, carbon-11, nitrogen-13, technetium-99, copper-64, zirconium-89, gallium-68, and lutetium-177. [12][13][14][15][16] In these systems, some steps of the tracer production process are performed using conventional macroscale setups (i.e., drying and activation of [ 18 F]fluoride upstream of the flow reaction, and purification of the crude tracer downstream of flow reaction), though some efforts have been made to implement them in a flow-like format. [17][18][19][20] Some flow systems can perform reactions using just 10 s of microliters for optimization purposes, resulting in low reagent and precursor consumption.…”