We propose the development and use of novel nanocomposite contrast agent devices (NCADs) as next generation X-ray and CT contrast agents for in vivo molecular imaging and spectroscopy that are also suitable for multi-modality imaging. This opportunity stems from two factors: 1) the unique properties offered by dendrimer templated hybrid nanoparticles (uniform but variable size, alterable surface and changeable particle composition and architecture) and 2) the possibility to combine the properties of the uniform macromolecular host with the required properties of the inorganic guest according to the specific requirements of medical imaging. These imaging agents will be synthesized as uniform composite nanoparticles from poly(amidoamine) dendrimer hosts and amorphous or semicrystalline, small inorganic guest domains bound within the host templates. The nanoparticles will be characterized by polymer at the University of Michigan and materials characterization methods including neutron and X-ray scattering techniques at Argonne National Laboratory. Each NCAD will have a specific size (5, 10 and 25 nm), a specific surface (well-defined positive or negative net surface charges, as well as neutral surface with various degrees of hydrophilicity) and will carry different non-toxic metals or metal compounds, either individually or in combinations. The properties of the host and guest components can be separately selected, developed, and optimized. The well-defined host will permit (or prevent when needed) size related and surface recognition targeting of tissues and/or organs. NCADs of different sizes and surfaces will be developed and tested for use as a blood pool agent and as a nonnephrotoxic kidney specific contrast agent. We will prove this concept using tin and gold containing dendrimer nanocomposites and standard in vivo methods to assess toxicity (rat model) and demonstrate usefulness of the nanoscopic agents in animal angiography (imaging of arteries, veins, and adjacent soft tissue) by planar X-ray (canine model) and CT (rat model). Further methods to determine the biodistribution of NCADs and utilize multifunctionality include light (NSOM, fluorescence) microscopy and transmission electron microscopy of tissue samples. Conceptually these nanodevices will be applicable to a number of diseases and they can be developed to further expand the usefulness of the most readily available medical imaging instruments to identify illnesses in an early stage. They may also be used as building blocks to build modular nanoparticle devices that target specific tissues or cells and combine imaging, early detection, and delivery of therapeutics.
