MICROFLUIDIC-DIRECTED SYNTHESIS OF 18F RADIOACTIVE NANOSCALE LIPOSOMES FOR USE AS CONTRAST AGENTS IN POSITRON EMISSION TOMOGRAPHY (PET)

 

Donna M. Omiatek and Wyatt N. Vreeland

 

Liposomes have attracted interest in the biomedical community due to their relevancy in a number of potential clinical applications in the fields of targeted drug delivery and imaging diagnostics.  We have collaborated with the NIH Imaging Probe Development Center (IPDC) for the rapid, high-throughput synthesis of radioactive 18F-labeled nanoscale liposomes to function as long-term circulating PET probes for imaging of whole-body venous or arterial vascular systems.  Common production technologies (e.g. film hydration or alcohol injection with subsequent membrane extrusion or high pressure shearing) of these liposomal probes require processing times that limit their wide-spread clinical implementation due to the extremely short shelf-life of 18F (i.e. < 2 h).   To promote the radioactive viability of these probes, we have developed a new technology for liposome synthesis that utilizes disposable microfluidic devices to enable an alternative synthetic strategy for the instantaneous self-assembly of monodisperse nanoscale liposomes through the controlled mixing of an alcohol-soluble lipid solution and a buffered aqueous solution.  By finely tuning the flow velocities of these fluid streams, we have demonstrated control over particle size and size distribution at the point of formation, obviating the need for lengthy post-formation size-homogenization strategies.  Here, we summarize the optimal preparative conditions for the microfluidic generation of 18F-labeled liposomes, as well as their application as novel contrast agents in PET imaging.