UCLA

Production of a positron emission tomography (PET) tracer involves three stages: production of the radioisotope, radio-labeling and purification of the tracer, and quality control (QC) testing of the final product (if the tracer is used in humans). Though the production of the positron-emitting radioisotope requires expensive and complex instrumentation (e.g. cyclotron or generator), in many cases, the radioisotope can simply be obtained from a commercial source. The radio-labeling and purification step is performed by machines called radiosynthesizers, which perform chemical synthesis and purification processes in a remote-controlled or automated manner within radiation-shielded “hot cells”. Quality control testing is performed to ensure each batch of radiopharmaceutical is safe prior to use in human subjects, and requires several analytical chemistry instruments. Though a couple of PET tracers are routinely available in final form from commercial sources, most other tracers need to be specially manufactured and quality tested at the researcher’s facility.

Advances in radiosynthesizer technology such as automation, programmability, and reagent kits simplify the production of diverse tracers. Furthermore, recent efforts in miniaturized synthesizers based on microfluidics aim to reduce equipment cost, shielding and lab space needs, and quantities of expensive reagents, to make it more affordable to produce custom batches of PET tracers on demand.

In the context of these emerging technologies, quality control testing still remains a bottleneck due to the high cost of the many expensive instruments, specially-trained staff, and documentation needed to determine the purity and ensure the levels of all potential contaminants are below acceptable limits. Several companies are developing automated systems for quality control testing to alleviate some of these issues. However, high cost and large size remain obstacles. We have therefore explored the use of microfluidic analytical chemistry techniques to address these remaining critical issues. In this dissertation, the feasibility of using capillary electrophoresis (CE) to analyze the chemical purity of PET tracers is investigated as a compact and inexpensive replacement for high performance liquid chromatography (HPLC) and other techniques that are normally used for this purpose. After establishing that CE has sufficient performance (comparable to HPLC) using several example chemical systems, the design, development, and characterization of a microscale chemical purity testing system are presented, along with a discussion of its capabilities and limitations. Overall, it appears that microchip CE could be used instead of HPLC for performing many of the required QC tests of PET tracers.