Utilization of gold containing nanomaterials for targeted radiotherapeutic and diagnostic applications

Abstract

6520-00/(S Several different investigations are discussed in this dissertation, with the common thread of using gold-containing nanomaterials in nuclear medicine applications. Gold nanoparticles form a non-toxic surface layer that can be easily functionalized with biological targeting agents. The first set of experiments focuses on attempts to develop cancer therapeutic and imaging agents using the radionuclides 198/199Au. Gold nanoparticles with both passive (gum arabic coated) and active (bombesin) targeting are examined. Additionally, the possibility of attaching a chelate to bind the PET imaging radionuclide 64Cu with DTDTPA is explored. The second area of emphasis focuses on developing a nanoparticle capable of retaining the radioactive decay daughters of the in vivo α generator 225Ac. This generator system produces 4 successive α emissions in its decay chain. However, daughter products escape and cause renal toxicity. A LnPO4 nanoparticle coated with gold can both retain the energetic daughter products in the decay chain and be easily functionalized to deliver radiation to biologically relevant targets in vivo. Nanoparticle technology allows for the combination of multiple therapeutic and imaging modalities by a single platform. Unlike conventional approaches, the multi-atom nature of nanoparticles allows for delivery of large, varied payloads to biological receptors. The nanomaterials discussed here can theoretically be used for any combination of PET/SPECT imaging, MRI contrast, or α/β- radiotherapy.