News

December 15, 2005

New Microchip Technology Assembles FDG, Potentially Many Other PET Probes

University of California, Los Angeles

A microchip device no bigger than a stamp may soon cheaply and efficiently produce FDG for human imaging. The computer-controlled "lab-on-a-chip" device, designed by graduate student Chung-Cheng Lee of the California Institute of Technology (CalTech; Pasadena) and colleagues, can rapidly prepare doses of unstable compounds like the PET scan probe from basic chemical feedstock and F-18. The technology has the potential produce a wide variety of molecular imaging agents.

The design is the result of a collaboration between academic and industrial researchers at CalTech, the David Geffen School of Medicine at the University of California at Los Angeles (UCLA), Howard Hughes Medical Institute in Los Angeles, Stanford University School of Medicine (Stanford, CA), Siemens, and Fluidigm Corporation.

"Multistep Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics," by Chung-Chen Lee, et al., was published in the December 16 issue of the journal Science (2005;310:1793–1797). As a proof of principle, the group of academic and commercial scientists demonstrated that FDG could be synthesized by the stamp-size chip. These chips are similar in design to integrated electronic circuits, except that they are made of fluid channels, chambers, and valves that allow them to perform multiple chemical operations, synthesizing molecules and labeling them with radioisotopes. All the operations of the chip are controlled and executed by a standard office computer.

The chips use microfluid circuitry to integrate a number of chemical processes in a small space with no opportunity for cross-contamination, and it is possible to design and build circuits to synthesize new compounds in about two days, according to Hsian-Rong Tseng, PhD, coauthor and assistant professor of molecular and medical pharmacology, Crump Institute for Molecular Imaging, UCLA.

Commercialization of the new technology is well on the way, according to Stephen Quake, PhD, coauthor and a professor of bioengineering at Stanford University School of Medicine. Integrated microfluidic chips can simplify the production of radiopharmaceuticals, lowering the cost and dramatically accelerating the development of new molecular imaging probes for PET.

FDG was produced on the chip and used to image glucose metabolism in a mouse with a Siemens microPET scanner. The Science paper postulated that this technology can also produce the amount of FDG required for human studies. More importantly, the paper describes the use of a new base technology for producing and delivering a diverse array of molecular imaging molecules and radiolabeled drugs for diagnostic molecular imaging and drug development.

"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," said Tseng.

There is a vast distribution network of manufacturing sites throughout the world producing PET imaging molecules for hospitals, universities, and pharmaceutical companies. The goal is to integrate these new chips into a commercially produced, table-top device controlled by a PC. Owners of the device would order chips designed to produce specific imaging molecules. Doses could then be produced whenever needed from chemical feedstock and radioisotopes. Technology that enables users to quickly manufacture a variety of probes on an ad hoc basis could fuel growth in the diversity of PET applications.

The study authors and their participating institutions and companies include: Hsian-Rong Tseng, Guodong Sui, Chengyi Jenny Shu, Alek N. Dooley, Nagichettiar Satyamurthy, and SNM members David Stout and Michael Phelps, all of the David Geffen School of Medicine at UCLA; Owen N. Witte of UCLA and the Howard Hughes Medical Institute in Los Angeles; Chung-Cheng Lee, Young-Shik Shin, and Arkadij Elizarov of CalTech; James R. Heath of UCLA and CalTech; Stephen Quake of Stanford; Hartmuth Kolb of Siemens Biomarker Solutions, Culver City, CA, and UCLA; and Jiang Huang, Antoine Davidon, and Paul Wyatt of Fluidigm Corporation, San Francisco, CA.

The research was supported by a Department of Energy grant to the UCLA Institute for Molecular Medicine, the National Cancer Institute, the Norton Simon Research Foundation, the UCLA National Cancer Institute molecular imaging training grant, and commercial support from Siemens and Fluidigm.