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.
ABSTRACT
The indications for joint arthroscopy continue to expand rapidly as technology advances. Surgeons and patients alike are realizing a progression of benefits related to lower morbidity associated with arthroscopic procedures supplanting open surgeries. However, it is important in each new application to critically evaluate the operative expertise, theoretical advantages, and actual outcome data before deciding the relative benefit of an arthroscopic procedure versus an open one. This is especially true for shoulder surgery because of the complex and restricted anatomical spaces available for insertion of an arthroscope. Additionally, orthopaedic surgeons are just now developing a clear understanding of the pathology of the glenohumeral joint and subacromial space, and the indications for intervention in these areas. Although the practice of shoulder arthroscopy is still in an early stage of development, it was actually first described by Burman in 1931. In his cadaveric studies, with instruments that look remarkably similar to ours today, he describes both the portal placements and the glenohumeral anatomy in some detail. It was Burman's opinion that the shoulder was the easiest and most consistent of all joints to visualize.
