1. Development of Molecular Imaging Probes

Molecular imaging probes represent an important and growing class of chemical compounds for biology, pharmaceutical sciences and medicine.  In conjunction with PET imaging, the identification of molecular imaging targets and the development of new radiolabeled molecular probes for those targets are crucial for expanding the capability of in vivo molecular imaging for biological research, molecular diagnostics and drug discovery.  The long term objective of this pilot project is to create a universal technology platform founded upon integrated microfluidic systems in order to generalize and accelerate the discovery and production of new PET imaging probes. We collaborate extensively with chemists, physicists and biologists from three academic institutions including UCLA, Caltech and Stanford.  Among many ongoing research projects in our joint research team, we describe two of them as follows:

• Multi-Step Syntheses of Radiolabeled Imaging Probes Using Integrated Microfluidics. 

We have demonstrated a technology platform for performing multi-step chemical syntheses in automated integrated microfluidic devices. The synthesis of an [18F]radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), in an integrated microfluidic device was chosen as a proof-of-principle study. This multi-step synthesis composed of five sequential processes ― [18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection ― was demonstrated with high radiochemical yield and purity, and shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography (PET) imaging studies in mice were prepared. These results constitute a proof of principle for performing sequential synthetic processes at the nanogram to microgram scale in an automated fashion, and also demonstrate how integrated microfluidics chips can generalize, accelerate, diversify and lower the cost of labeling processes for a wide range of molecular imaging probes. Currently, our research efforts focus on utilizing the microfluidic platform for preparing other existing [18F]-labeled PET imaging probes, i.e., 3’-[18F]fluoro-3’-deoxythymidine (FLT) and 2-(1-(6-[(2-[18F] fluoro-ethyl)(methyl)amino]-2-naphthyl) (FDDNP), as well as new radiolabeled PET imaging probes.

microPET/microCT image of a tumor-bearing mouse injected with [¹⁸F]FDG produced in a microfluidic chip

A Microfluidic Platform for Production of Radiolabeled Imaging Probes

Movie. Automated  FDG Synthesis in Action 

Download. AutoCAD file for chip design

• Screening High-Affinity PET Imaging Probes by Performing in situ Click Chemistry on a Microfluidic Chip. 

A new type of microfluidic chip has been designed and fabricated to conduct a number of in situ click chemistry experiments in parallel.  The overall goals are (i) to develop new general technology platforms based on the fragment-based in situ click chemistry approach in combination with microfluidics technologies to simplify, accelerate and diversify the production of PET probes and biomarkers, and (ii) to develop new classes of PET probes that exhibit high affinities for disease-related targets and that enable “high-performance” molecular imaging. We expect microfluidic technologies to complement in situ click chemistry. Microfluidics will allow us to reduce protein consumption by 2 – 3 orders of magnitude, compared to traditional systems. These devices will make the development of PET imaging probes cheaper and more efficient.

Movie. 32 In situ click reactions inside a microfluidic circuit 

Download. AutoCAD file for chip design

Collaborators:

Heath Group at Caltech  

Kolb Group 

Dr. Mike Phelps 

Quake Group at Stanford 

Satyamurthy Group 

Witte Group 

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Last modified: 01.20.2008