The long-term goal of this research is to develop a multifunctional nanoparticulate contrast agent for cancer imaging that, through proper surface engineering, affords site specificity coupled with both diagnostic and therapeutic capabilities in a single package. The nanoparticulate material that will be investigated is one that the PI has employed in the development of advanced ceramics and inorganicorganic hybrid composites. The ability to surface engineer the elemental composition of the ceramic nanoparticle and the ability to effectively control the organic functionalities at the surface of the particulates have been established. What has not been established is the effect that process conditions have upon the physical properties relevant to their use as contrast agents, and their behavior in animal models. The preliminary results that have been obtained with these materials, r1 > 30 mM(-1)s(-1), with no effort to optimize the composition, clearly establishes that the GadAL materials warrant the proposed investigation. The goal of this R21 application is to establish benchmark values for the physical properties of a nanoparticle based system with respect to stability, relaxivity, and particle size for use as a magnetic resonance imaging (MRI) contrast enhancement agent. The benchmark properties will be used to determine if the nanoparticulate materials are suitable for further study. The interdisciplinary project team we have assembled for this R21 research effort, SRI's Physical Sciences, Biopharmaceutical, Policy Divisions and from Alerion, Inc., who will be a subcontractor on this application, have the capability and expertise necessary to perform the materials synthesis and analysis for optimization of the nanoparticulate contrast agent performance, conduct the toxicological and pharmacokinetics analysis, and begin the process of agent development should the results of this application warrant.
