This proposal seeks to develop new contrast agents for in vivo microCT x-ray imaging based on non- toxic gold nanoparticles that would provide additional useful features over current agents including: a) longer imaging times, b) higher contrast, and c) targeted, tumor-specific imaging. Physically, gold is a better contrast element than iodine for both microCT and clinical CT because, for microCT the beam's energy spectrum can tailored to be above its 12-14-keV L-edge (e.g. 50 kVp), while for clinical CT it can be tuned to be above gold's 80.7-keV K-edge (e.g., 150 kVp with Cu filtration), thus optimizing the image contrast-to-noise ratio for both applications. Phase 1 work has succeeded in imaging 20 mu m blood vessels and obtaining vascular casts in live animals with this approach, never before achieved. Small, orthotopic colon tumors were also detected in vivo using gold nanoparticles. Phamacokinetics and toxicity were also shown to be acceptable. Gold-antibody conjugates were found to be specifically targeted to colon tumor cells in vitro. In Phase II, targeted molecular imaging will be extended to animals. Anti-CEA antibody-gold nanoparticles will be optimized to detect small human colon tumors in a mouse model by microCT. Additionally, vascular molecular markers in tumors will also be targeted. Further toxicity testing will be done and used to demonstrate or refine production of non-toxic gold contrast agents. R&D effort will result in products offered that other investigators can use. The benefits of this work will be: a) the enabling of high resolution in vivo CT contrasted detection and study of colon tumors and their vasculature, b) the introduction of contrast agent products that will then be available to other researchers using microCTs that will enable vascular and targeted imaging, c) to address and overcome the remaining obstacles to make these agents acceptable for human use. If successful, this effort will produce superior blood pool agents and the first targeted CT contrast agent, goals that have been difficult to achieve by other approaches. ? ? ?
| Hainfeld, J F; O'Connor, M J; Dilmanian, F A et al. (2011) Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions. Br J Radiol 84:526-33 |
| Joshi, V N; Mitra, D; England, M D et al. (2010) Large Covalently Linked Fluorescent and Gold Nanoparticle Immunoprobes. Microsc Microanal 16:966-967 |
