Rapid Microfluidic Production of PET Biomarkers

Positron Emission Tomography (PET) is a valuable non-invasive imaging tool for the diagnosis and follow up of such diseases as cancer, heart disease, and Alzheimer¿s. The DOE has identified a need for novel probes and radiolabeled compounds for PET, along with advanced methods to deliver them. Short-lived radioactive tags such as [18F] fluoride ion and [11C] carbon can be attached to molecules or chemical biomarkers prior to injection into patients or small animals, and then imaged at various stages of biodistribution. For example, [18F] fluorodeoxyglucose has been used to monitor glucose metabolism in the body. Other more specific biomarkers ¿ e.g., [18F] fluoromisonidazole, a marker for hypoxia, and [18F] fluorothymidine, a marker of proliferation ¿ have been developed, but have been extremely difficult to bring to market. Much of the problem is that these specialized biomarkers are difficult to synthesize, often have poor yields, and require expensive precursors. This project will develop a microfluidic platform to synthesize PET biomarkers. The technology will reduce processing times and reagent usage by a factor of 30 to 100. In Phase I, small, low cost, modular microreactor cartridges were developed and used routinely to synthesize a host of PET biomarkers, each with better yields than conventional chemistry and each within 1 to 2 minutes. Phase II will develop processes to enable complex multi-step microfluidic synthesis with intermediate purification, multiple organic solvents, and micro- purification of the final product. Commercial Applications and other Benefits as described by the awardee: The rapid biomarker production technology should reduce production time, reagent consumption, and manpower requirements. Commercial applications exist in clinical, pre-clinical, and drug discovery markets