Radioactive Au for potential radiotherapeutic application

Title from PDF of title page (University of Missouri--Columbia, viewed on Aug. 19, 2010).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Thesis advisor: Silvia S. Jurisson, Ph.D., and Cathy S. Cutler, Ph.D., Co-Advisor.M.A. University of Missouri--Columbia 2010.Radioactive gold-198/199 can be used in therapeutic radiopharmaceutical agents to combat cancer. In this thesis, two projects involving the development of radioactive gold-198/199 are described. The first project discusses the first tetradentate Au(III) bis-thiosemicarbazones (Au-ATSM/PTSM) that were synthesized and characterized. At radiotracer levels using Au-198/199 required a high ratio of gold-to-ligand (1:>100). Our studies indicated that Au(III) can be coordinated to both ATSM or PTSM ligands. These results allowed for further investigation into a variety of bis-thiosemicarbazide derivatives to coordinate Au(III). The second project involved radioactive gold nanoparticles (AuNPs) that were synthesized, characterized, and evaluated in vivo. Three stabilizing agents (starch, gum Arabic, and epigallocatechin gallate (EGCG)) were studied to determine the ease of syntheses of AuNPs, relative stability to aggregation, and toxicity in vivo. Incorporating radioactive Au-198/199 allowed for biodistribution studies by three administration routes (intravenous (IV), intraperitoneal (IP), and intratumoral (IT) injections) in prostate cancer bearing mice. These studies indicated that radioactive (Au-198/199) AuNPs can be used to treat prostate cancer by IT injection. Two of the three stabilizers (gum Arabic and EGCG) were further evaluated for treating prostate tumors in mice. The results indicated that the radioactive AuNPs reduced the tumor size with no apparent toxic effects.Includes bibliographical reference

Production and optimization of 198/199 gold nanoparticles for potential use in cancer therapy [abstract]

Abstract only availableRadiopharmaceuticals are used to diagnose and treat a number of diseases such as bone cancer and non-Hodgkin's lymphoma. A radiopharmaceutical typically consists of a targeting molecule that selectively targets certain tumors. The targeting molecule is labeled with a radioactive atom(s) that delivers a dose of radiation to the tumor. The radioactive properties of Au-198 ([beta]- = 0.96 MeV; [gamma] = 411 KeV) and Au-199 ([beta]- = 0.45 MeV; [gamma] = 158 KeV) with their beta (therapeutic) and gamma (imaging) emission make them valuable candidates for both therapeutic and imaging applications. Gold nanoparticles have several properties that make them particularly interesting for use in radiopharmaceuticals. They are stable in vivo, have multiple atoms per particle and are small enough in size to deliver a radioactive dose directly to cancer cells. The purpose of this study was to gain a better understanding of the binding properties of the nanoparticles with reducing and stabilizing agents. This knowledge will aid in future attempts to label the particles with various antibodies and peptides for tumor targeted delivery of the drug. Next, investigate the relationship between particle size and the amount of reducing agent used was studied with varying amounts and types of carbohydrate stabilizers. Our goal is to establish a library of nanoparticles with varying sizes that can be conjugated with different biomolecules that are selective for receptors over expressed by the diseased tissue. In future studies we also plan to pursue an indirect method of preparing radioactive Au-199 nanoparticles at carrier free levels from beta decay of Pt-199.Life Sciences Undergraduate Research Opportunity Progra

Comparative oncology and clinical translation of glyco protein conjugated gold nano therapeutic agent (GA-198AuNP) [abstract]

Nanoscience Poster SessionAs part of our efforts toward clinical translation of GA-198AuNP, our studies are focused on therapeutic efficacy of nanoparticulate GA198AuNP agent in dogs with prostatic carcinoma. The overall goal is to gain clinical insights on therapeutic efficacy of GA198AuNP in a large animal model. We have performed a phase I clinical trial using GA-AuNP administered intravenously or intratumorally by injection or infusion. CT scans were performed prior to injection and 24 hours post injection in 3 of the 4 dogs. Following injections, dogs were allowed further treatment as recommended by the primary attending clinician. Four dogs have been treated to date. Complications related to GA-AuNP treatment were not observed, and all 4 dogs received adjunctive treatment with radiation therapy and/ or chemotherapy. These preliminary studies have clearly provided compelling evidence on the therapeutic potential of biocompatible GA-AuNP for their utility as novel therapeutic agents in treating various types of inoperable solid tumors. Intra-tumoral and intravenous administration of GA-AuNP is safe in dogs with spontaneously occurring tumors. As further therapeutic efficacy studies continue, the outcome of this clinical trial in a large animal model will generate therapeutic efficacy data which will be used for filing IND application for Phase I clinical trial studies. This clinical translation effort provides significant advances in terms of delivering optimum therapeutic payloads into prostate cancers with subsequent reduction in tumor volume, thus may effectively reduce/eliminate the need for surgical resection. This presentation will include details of clinical translation of GA198AuNP in prostate tumor bearing dogs