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Issue 42, 2017
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Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system

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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.

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

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Publication details

The article was received on 19 May 2017, accepted on 05 Sep 2017 and first published on 05 Sep 2017

Article type: Paper
DOI: 10.1039/C7DT01830D
Dalton Trans., 2017,46, 14669-14676
  • Open access: Creative Commons BY license
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    Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system

    Z. Liu, K. S. Schaap, L. Ballemans, R. de Zanger, E. de Blois, M. Rohde and E. Oehlke, Dalton Trans., 2017, 46, 14669
    DOI: 10.1039/C7DT01830D

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