Comparison of different methods for removing metals from resins for applications to radiochemical seperations

Abstract only availableMetallic contamination has been a problem for many years in the environmental field. Soil, water and air have been polluted by many different trace metals that finally affect humans by consumption of natural products, liquids and simple respiration, and have the potential of producing some toxicity in the body, leading to different illnesses such as cancer. On the other hand medical and scientific studies have found many metals such as the radiolanthanides and M(3+) metals, to be useful for therapeutic purposes, including cancer treatment, and targeting specific organs in the human body by the use of radioactive isotopes. The overall goal of this project was to compare the different techniques for cleaning various resins being used in the production of radiolanthanides at MURR. This was done to determine what metals and in what quantities these metals were removed by each method. Resins are known to contain extraneous metals such as copper, zinc, calcium and iron, which can leach out of the resin and contaminate the sample of interest resulting in low radiolabeling yields. The methods examined were different acid washes of various molarities and the use of different ligand systems (chelators) to determine which method would remove the most metals without affecting the resolving power of the resins. A variety of resins that are being investigated for performing separations, extractions and clean up of radiolanthanides of interest for radiotherapy were examined. Radiolanthanides are being developed and bound to biomolecular targeting agents to treat and provide palliative care for a variety of cancers. The purity of these radiolanthanides are essential as impurities in the original target material can result in unwanted impurities that can lead to environmental waste issues and dose concerns to workers and patients. In addition, since the chelates that attach these radiolanthanides to the targeting molecule are nonselective and will bind all +3 and many +2 metals, this would lead to low radiolabeling yields and therefore result in a lower dose being delivered to the target organ. The radiopharmaceutical developed by means of this procedure is one that selectively targets only a certain receptor and effectively irradiates only the tumor without affecting the surrounding organs. Thus is a non-invasive treatment that is better tolerated by the patients, as compared to other treatment methods such as chemotherapy, radiation treatments and surgery. The resins were washed and the eluents analyzed by ICP-MS (Inductively Coupled Plasma Mass Spectrometry). This technique determines the amount of metals present in the eluents collected from each wash. The elements expected to be found in these samples are the common metals found in the environment, like iron, calcium, aluminum, zinc, chromium, copper, nickel, etc. Furthermore, by performing simple radiolabeling studies with Lutetium-177 and 1,4,7,10-tetraazaciclododecane-1,4,7,10-tetraacetic acid (DOTA), a ligand commonly used to bind radiolanthanides, the washes were compared. The percentage labeled complex was compared to evaluate which method resulted in the best extraction of unwanted metals.NSF-REU Radiochemistr

Reduction of rheniumV oxo Schiff base complexes with triethylphosphine

Abstract only availablePioneering techniques for therapeutic treatment of cancers involve targeting cancer sites with strong beta-emitting radionuclides, thereby destroying the cancer cells. This is achieved by coordinating the radioisotope to a very chemically stable environment and linking it to a specific biologically active targeting molecule, which interacts with particular cancer cells. Radioactive isotopes of rhenium possess characteristics of such a nuclide. The focus of our research is to investigate two possible pathways for the reaction of [ReOX(Schiff base)] with phosphine ligands, one a mono-substituted ReV complex and one a di-substituted ReIII complex. The preferred ReIII complex is lower in oxidation state and more kinetically inert or stable relative to ReV. For practical applications it is necessary to have an extremely stable in vivo radionuclide complex which can be conjugated to a suitable biological targeting agent. The rigid sal2phen ligand, where Sal2phen is a tetradentate Schiff base ligand, was investigated to determine if the ReIII could be synthesized from the ReV starting complex [ReVOCl(Sal2phen)]. [ReVOCl(Sal2phen)] was reacted with triethylphosphine (PEt3) in attempts to yield the ReIII complex trans-[ReIII(PEt3)2(Sal2phen)][X]. Previous work indicated that the strongly reducing and strongly nucleophilic PEt3 might yield the ReV product from [ReVOCl(Sal2phen)]. The synthesized coordinated complex was reacted with an quaternary ammonium salt, ammonium hexaflurophosphate (NH4PF6), to induce crystallization of target compound [ReIII(PEt3)2(Sal2phen)][PF6]. Preliminary 1H-NMR, 31P-NMR, and infrared spectroscopy spectra indicate the formation of cis-[ReVO(PPh3)(Sal2phen)][X]. FTIR shows the presence of the Rhenium oxo group; 31P-NMR and 1H-NMR indicate the presence of ReV and a 1:1 PEt3 : Sal2phen complex. Single crystal x-ray diffraction, mass spectroscopy, and elemental analysis are additional methods of characterization.NSF-REU/NIH Program in Radiochemistr

Reduction of rhenium (V) oxo Schiff Base Complexes with triphenyl phosphine ligands

Abstract only availableOne approach to the treatment of cancer is to direct beta-emitting radionuclide to the cancer site where the radiation destroys the cancer cells. This can be achieved by coordinating the radioisotope in a very stable environment and linking it to a specific biological targeting molecule, which interacts specifically with particular cancer cells. It is necessary to have extremely stable in vivo radionuclide complexes so that limited amounts of radiation are released to other parts of the body before the radionuclide can reach the cancer cells. Isotopes of radioactive Rhenium are characteristic of such a nuclide. Our emphasis was to obtain a Rhenium (III) metal ligand complex since the lower oxidation state is more kinetically inert relative to Rhenium (V). The method employed was to first produce the ReV-ligand complex, [ReVOCl(Sal2phen)], by reacting a 1:2 molar ratio of TBA[ReVIIOCl4] to Sal2phen. Next, [ReVOCl(Sal2phen)] was reacted with three equivalents of triphenylphosphine to determine whether a mono-substituted ReV complex or a di-substituted ReIII complex was formed. After purifying the product by solvent extraction, the coordinated complex was reacted with ammonium hexaflurophoshate, NH4PF6, to induce crystallization of the target compound, [ReIII(PPh3)2(Sal2phen)][PF6]. Preliminary 1H NMR, and FT-IT spectra suggest formation of trans-[ReIII(PPh3)2(sal2phen)]PF6. The Re=O stretch at 951.36 cm-1 observed for [ReOCl(sal2phen)] in the IR spectrum is missing from our product, implying the Re (III) product has been formed.Stevens' Chemistry 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

Reaction of Rhenium(V) with a Mixed Donor, Phosphine Thioether [abstract]

Abstract only availableFaculty Mentor: Dr. Silvia Jurisson, RadiochemistryRadiopharmaceuticals are drugs labeled with a radioisotope. The radiopharmaceuticals are used in the diagnosis of cancer while functioning like materials in the body without any pharmacological significance. The bifunctional chelate approach for radiopharmaceuticals involves a biomarker that targets the tumor linked to a chelate that holds the radioisotope. This type of research is possible because tumors have a higher density of surface receptors for specific peptides than normal cells. Utilizing the bifunctional chelate approach, a radiopharmaceutical can be localized at tumor sites. Chelation is the binding of a ligand to a metal ion. The ligands bind to the metal atom to produce a heterocyclic ring. The chelate is a mixed donor, phosphine thioether. Rhenium is an important radiopharmaceutical component because it offers a non-radioactive model for Technetium. 186Re and 188Re are therapeutically usefully based on their half-lives and beta energies emitted. Re(V), in the form of ReOCl3(PPh3)2, was reacted with a phosphine-thioether ligand. The product has a dioxo core and was fully characterized

Reducution of rhenium(V)-oxo schiff base complexesith triphenyl phosphine ligands [abstract]

Abstract only availableFaculty Mentor: Dr. Silvia Jurisson, ChemistryThe purpose of this research is to produce radiopharmaceutical drugs for the possible use in therapy and diagnosis of cancer. A radiopharmaceutical drug is composed of a radioactive element contained within chelating agent and linked to a biological targeting molecule. This can be achieved by complexing the radioisotope and conjugating the complex to a biologically active targeting molecule, such as a peptide antibody or antibody fragment. The biological targeting molecule directs radiation to specific peptides, antibodies and antibodies' fragments. The amount of dosage is limited to non-targeted tissue that occurs when free radionuclide is released from a decomposing molecule. Higher kinetic stability will maximize the localization of the radioisotope to the cancer sites and minimize the radiation dose to non-target tissues. This research was a continuation to seek the best pathway that would easily enable us to synthesize a kinetically inert metal complex [Re(Sal2Phen)] attached to a ligand. The rigid Rhenium(V)-oxo Schiff base complex is found in the following form: [ReO(Sal2Phen)Cl]. Initially salicylic aldehyde reacted with bis-2-phenlinediamine to get sal2phen. This tetradentate Schiff base ligand was reacted with TBA [ReOCl4] yielding [ReOCl(Sal2Phen)]. The reduction of Rhenium(V)-oxo core to Rhenium is obtained by reacting [ReO(Sal2Phen)Cl] with a triphenyl phosphine (PPh3) in dichloromethane and ethanol. Products obtained from this reaction were 1[Re(Sal2Phen)(PPh3)2], 2ReCl(Sal2Phen)PPh3, and 3[ReO(Sal2Phen)PPh3].Analysis of the major product were performed through crystals through mass spectrometry, hydrogen and phosphorus NMR, infrared spectra and x-ray crystallography

Ga-Ga over 68Ga: Novel chelates for PET heart imaging [abstract]

Abstract only available; Images included in PDF that are absent in abstract description.Heart disease remains one of the leading causes of death in the United States. Improved, function-specific imaging agents promise to augment current diagnostic techniques, leading to better treatment and fewer deaths. Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) provide physiological rather than anatomical imaging systems. As such, they non-invasively probe tissue function with greater accuracy than other imaging techniques. Since functional abnormalities occur well before anatomical changes, these scans can lead to earlier diagnosis. In PET imaging, a directing agent binds to a positron-emitting material and carries the radioisotope to a specific tissue (in our project, the heart) where the isotope decays, emitting a positron. Current PET imaging agents, such as 18F, have short half-lives and must be administered at or near the production facility (cyclotron). However, one promising positron emitting radiometal, 68Ga (t1/2 = 68 minutes), comes from a Ge/Ga parent/daughter generator system. In such a generator system, a "parent isotope" (68Ge, t1/2 = 271 days) with a long half-life decays into a useful "daughter isotope" with a short half-life. Periodic elution provides the daughter isotope in high specific activity. In our case, 68Ge can be transported anywhere in the world, where it generates a viable PET agent without the constraint of an on-site cyclotron. Our work focused on Schiff base and aminothiolate ligand systems. Specifically, we bound, characterized, and analyzed the Sal2Phen, Acac2Pn, ATSM, and PTSM ligands with non-radioactive gallium on the milligram level. In future research, complexes will be created analogously on the radioactive level (nanogram or picogram quantities) and compared to their thoroughly characterized milligram-scale equivalent. The compounds will be tested for stability in a biological model before progressing to animal studies and, potentially, human drug testing. GaAcac2Pn GaSal2Phen GaATSM GaPTS