Batch-reactor microfluidic device: first human use of a microfluidically produced PET radiotracer

Lab Chip. 2013 Jan 7;13(1):136-45. doi: 10.1039/c2lc40853h. Epub 2012 Nov 7.

Abstract

The very first microfluidic device used for the production of (18)F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [(18)F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on "split-box architecture", with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [(18)F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880.

MeSH terms

  • Benzamides / chemistry
  • Benzamides / isolation & purification
  • Benzamides / pharmacokinetics
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Equipment Design
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / isolation & purification
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods*
  • Positron-Emission Tomography / instrumentation
  • Positron-Emission Tomography / methods*
  • Radioactive Tracers
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / isolation & purification
  • Radiopharmaceuticals / pharmacokinetics
  • Software
  • Tissue Distribution

Substances

  • Benzamides
  • Fluorine Radioisotopes
  • Radioactive Tracers
  • Radiopharmaceuticals
  • fallypride