January 9, 2006
Microfluidics Device Makes Radiolabeled Imaging Agents
New Microchip Technology for Medical Imaging Biomarkers of Disease Developed
A multi-institutional team of investigators has developed a new technology using integrated microfluidic chips for simplifying the production of radioactively labeled molecules used in positron emission tomography (PET). This technique should lower the cost and increase the versatility of PET as a means of imaging cancer and assessing the effectiveness of therapy. PET has been shown to improve significantly the detection of cancer, detect recurrence of cancer, and help select the right therapy for individual patients.
The vast majority of PET scans done today employ a version of the sugar glucose, called fluorodeoxyglucose (FDG) that is labeled with the radioisotope fluorine-19. Glucose is a critical fuel for cells throughout the body to perform their normal functions. For example, 95 percent of the energy for the brain to function comes from glucose. In addition, cancer cells increase their metabolism of glucose about 25-fold. Cells take up FDG as if it was glucose, but are then unable to use it as an energy source. As a result, FDG accumulates in cells at a rate that correlates well with how much energy a cell is using.
Writing in the journal Science, a team headed by Hsian-Rong Tseng, Ph.D., at the University of California, Los Angeles, and Stephen Quake, Ph.D., at Stanford University, demonstrate a programmable microfluidics chip that can dramatically accelerate the development of many new molecular imaging molecules for PET. As a proof of principle, this group of academic and commercial scientists demonstrated that FDG could be synthesized on a "stamp-size" chip. These chips have a design similar to integrated electronic circuits, except they are made up of fluid channels, chambers, and values that can carry out many chemical operations to synthesize and label molecules for PET imaging. All the operations of the chip are controlled and executed by a personal computer.
Caption: Microchip for Production of FDG.
Courtesy of Hsian-Rong Tseng, Ph.D., University of California, Los Angeles.
FDG was produced on the chip and used to image glucose metabolism in a mouse with a specially designed PET scanner for mice produced by Siemens, called a microPET. The Science paper illustrates that this technology also can produce the amount of FDG required for human studies.
More importantly, the paper illustrates a new base technology for producing and delivering a diverse array of molecular imaging molecules and labeled drugs for use with PET. With a wider range of labeled compounds available, researchers will be able to more easily study aspects of cancer biology beyond cellular metabolic rate. For example, researchers could use this new microfluidics chip to create a labeled version of a drug under study, and then use the labeled drug molecule to track how it moves through the body and gets taken up by cancer cells.
"Chemists synthesize molecules in a lab by mixing chemicals in beakers and repeating experiments many times,” said Dr. Tseng. “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 microfluidics chip."
There is a vast distribution of manufacturing sites throughout the world producing PET molecular imaging molecules for hospitals, universities, and pharmaceutical companies. The goal is to integrate these new chips into a small control device operated by a PC that will be commercially produced, then to ship chips to users so they can produce whatever molecules they choose for molecular imaging with PET. These chips will be an enabling technology to fuel growth in the number and diversity of imaging molecules and applications of PET in biology and pharmaceutical research and in the care of patients.
This work, funded in part by the National Cancer Institute, is detailed in a paper titled, “Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.” Investigators from Fluidigm Corporation, in South San Francisco, CA, and Siemens Medical Solutions, in Culver City, CA, also participated in this study. An abstract is available through PubMed.