Digital chip synthesizes PET probes

A digital chip that pumps fluids rather than electrons is being groomed to synthesize and label PET radiopharmaceuticals. The chip, about the size of a postage stamp, promises to lower the overall cost of PET studies, while increasing the onsite options available to providers, according to a recent study.

Instead of performing mathematical functions, the PET synthesizing chip performs chemical operations under the control of a PC. The computer-controlled "lab-on-a-chip" device can rapidly prepare doses of PET probes using basic chemical feedstock and F-18. Its underlying technology can be easily leveraged to design and build circuits that make new compounds, according to study coauthor Hsian-Rong Tseng, Ph.D., an assistant professor of molecular and medical pharmacology at the Crump Institute for Molecular Imaging at the University of California, Los Angeles.

"Chemists synthesize molecules in a lab by mixing chemicals in beakers and repeating experiments many times. But one day soon, they'll sit at a PC and carry out chemical synthesis with the digital control, speed, and flexibility of today's world of electronics using a tiny integrated microfluidic chip," Tseng said.

FDG was produced on the chip and used to image glucose metabolism in a mouse with a Siemens microPET scanner. This technology can produce enough FDG for human studies, according to the research team, whose results were published in the Dec. 15 issue of Science.

In the paper, Tseng and his colleagues described how the chip can be programmed to make customized PET probes. The research involved collaboration of a team from CalTech, the UCLA David Geffen School of Medicine, Howard Hughes Medical Institute in Los Angeles, Stanford University School of Medicine, Siemens, and Fluidigm of San Francisco. FDG was synthesized on Fluidigm's proprietary Integrated Fluidic Circuits.

Fluidigm is a pioneer in the development of these chips, developing and distributing them for analysis and synthesis of biomolecules in nano- and pico-sized volumes. Its stated mission is to do for biology and chemistry what integrated circuits did for computer science.

The company's chips are similar in design to integrated electronic circuits, but they are made of fluid channels, chambers, and valves, which allows them to perform multiple chemical operations. The ones developed for PET applications synthesize molecules, such as glucose, and label them with radioisotopes. The microfluid circuitry integrates chemical processes in a small space yet offers no opportunity for cross-contamination.

Currently, FDG is synthesized using large volumes and masses of reactants with bulky and expensive electromechanic devices, requiring synthesis times of about 50 minutes. This process is complicated by the short 110-minute half-life of radio-fluorine, which places a premium on labeling and administering the agent to the patient. In contrast, FDG can be prepared using digital chips in about 15 minutes.

The efficiencies gained through the use of these chips may allow PET to be deployed more broadly, while providing the flexibility to produce a wide assortment of PET probes.