Agents containing one or more heavy Z (high atomic number) atoms offer substantial improvements in contrast and spatial resolution, while reducing the overall patient radiation dose. The objective of this proposed research effort is to prepare well-defined tantalum compounds as radiographic agents. Tantalum (Ta) has been used for decades as both a metallic implant and radiographic marker. The principal focus will be on cluster compounds that contain several tantalum atoms, thus enabling high X-ray attenuation. These compounds will be synthesized, characterized, modified, and screened for properties predictive of physiological compatibility. The ideal tantalum-based contrast agent (1) provides high X-ray attenuation and therefore high contrast, (2) is stable under physiological conditions, (3) is available in high concentration, (4) is non- toxic, (5) is injected easily, (6) resides in the ROI (Region of Interest) for a sufficient length of time to allow imaging, and (7) is then completely excreted from the body. Our hypothesis is that suitable contrast agents can be developed using tantalum as the heavy atom. The targeted properties of the Ta-containing materials are (1) a tantalum-dense cluster, (2) sufficiently modifiable surface to attain the other agent requirements. Promising agents will be evaluated as saturated solutions by X-ray absorption analysis. Signal to background determination will enable a ranking of the cluster-surface systems. Required dose scenarios will be extrapolated from the analysis of dilution series. After the in vitro testing is completed we will proceed to Phase II with animal trials to characterize safety and efficacy in vivo. Once these are established, then we will hopefully continue with clinical trials that will lead to the release of the agents for clinical use in humans.
The proposed tantalum clusters may substantially improve X-ray imaging technology as an alternative contrast agent with improved contrast allowing superior diagnostic imaging. They can potentially provide better imaging with smaller quantities of contrast agent, improved depth of penetration and reduced scattering, resulting in lower image noise as well as reduced radiation exposure. They can also provide better imaging for obese patients and an alternative contrast agent for patients allergic to iodine. ? ? ?
