LDRD Progress Report: Radioimmunotherapy using oxide nanoparticles: Radionuclide contaiment and mitigation of normal tissue toxicity.

Abstract

Radionuclides with specific emission properties can be incorporated into metalchalcogenide and metal-oxide nanoparticles. Coupled to antibodies, these conjugates could be injected into the bloodstream to target and destroy non-solid tumors or target organs for radioimaging. In the first year of this project, two types of radioactive nanoparticles, CdTe:125m Te and Y 2 O 3 : 170Tm were synthesized and coupled to antibodies specific to murine epithelial lung tissue. The nanoparticles successfully target the lung tissue in vivo. Some leaching of the radioisotope was observed. The coming year will explore other types of nanoparticles (other crystal chemistries) in order to minimize leaching. Body of ReportNanoparticles have been shown to couple to proteins and the resulting conjugates may find applications as targeted drug delivery systems or medical imaging diagnostic tools (Tiefenauer, Kuhne et al. 1993;Frey, Mantis et al. 1999;Akerman, Chan et al. 2002;Wang, Mamedova et al. 2002;Gao, Cui et al. 2004). These conjugates could be injected into the bloodstream to target and destroy non-solid tumors or target organs for Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging (for a review of small molecule analogs see (Goldenberg 2002)). The nanoparticle based drugs may also mitigate unintentional radiotoxic effects by effectively sequestering and retaining the radionuclides and daughter products.CdTe nanoparticles were selected for the first experiments because the techniques for synthesizing CdTe nanoparticles are well-developed and the surfaces can be easily modified to allow for protein coupling. The CdTe nanoparticles can be doped with small quantities of the radioisotope 125m Te (t 1/2 = 58 days) which emits low energy 35.5 keVrays with no complicating beta or alpha emission thus allowing for verification of antibody performance and nanoparticle fate within the test mice.Cadmium telluride nanoparticles doped with 125m Te were prepared based on the Peng method (Peng and Peng 2001) in which CdO reacts with 125m Te metal within trioctylphosphine micelles at 250 ºC. A reaction time of 5 min affords homogeneous and unaggregated 5 nm diameter nanoparticles. The CdTe nanoparticle surfaces were derivatized by mercaptoacetic acid (Wuister, Swart et al. 2003).