Therapeutic nanoparticles are designed to deliver drugs to designated tissues or cells while minimizing accumulation in non-target tissues. Real time imaging of therapeutic nanoparticles can potentially monitor the in vivo distribution and pharmacokinetic properties of a drug delivery system. In principle, imaging techniques should provide verification that a drug is accumulating in the desired tissue. Our group has designed cyclodextrin polymers to interact with nucleic acids or small molecule drugs to form therapeutic nanoparticles and one variant is currently in human clinical trials. Here, we describe the preparation of dual magnetic resonance imaging (MRI)/ positron emission tomography (PET) imaging probes that were designed to combine the high spatial resolution of MRI with the high sensitivity of PET imaging into a single imaging particle. We have constructed these particles to take advantage of the fact that the Caltech Brain Imaging Center (CBIC) is building the first dual PET/MRI instrument, such that both imaging modalities can now be performed concurrently without the need to move the animal. Our dual MRI/ PET imaging probes have size and surface properties similar to the therapeutic cyclodextrin nanoparticles and are expected to have similar in vivo distribution. The imaging particles contain superparamagnetic iron oxide nanoparticles coated in cyclodextrin polymers that are modified with Copper-64 labeled DOTA. The imaging particles have been injected systemically into tumor-bearing mice, and at doses greater than 10 mg Fe/ kg tissue, the imaging particles are detected in tumors by MRI. Additionally, the particles give time-dependent biodistribution in mice via PET imaging. Our current goals include PET and MRI studies to monitor the in vivo distribution of the imaging particles in order to determine the optimal size and targeting ligand necessary for tumor accumulation and minimizing reticuloendothelial cell uptake. Also, we plan concurrent imaging with both techniques using the dual PET/MRI instrument when it becomes available at Caltech.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA