Determination of conditions for optimum labeling of DOTA-Y3-Octreotate with terbium-161 [abstract]

Abstract only availableDOTA-Y3-Octreotate (DOTA-TATE) and other somatostatin analogs can be labeled with radionuclides for cancer-fighting applications. Specifically, the radiolanthanides are of great interest to the radiopharmaceutical industry because of their similar chemistries and assortment of radioactive properties. Terbium-161 (161Tb) is considered ideal for both radiotherapy and imaging because of its half-life (6.91 days), beta (0.59 MeV) and gamma (46-48 and 74 keV) emissions. In addition, carrier-free 161Tb will have a high specific activity, meaning less drug mass is necessary to deliver the required dose to the neuroendocrine tumor. Radioactive terbium was obtained at the University of Missouri Research Reactor (MURR) via neutron capture on gadolinium-160 (160Gd) to form gadolinium-161 (161Gd), which beta decays to 161Tb. To obtain carrier-free 161Tb, 160Gd contaminant was isolated from 161Tb using ion-exchange liquid chromatography. Various parameters were tested to optimize conditions for labeling DOTA-TATE with 161Tb: pH, buffer concentration, sample volume, incubation time using a water bath, and amount of activity. 161Tb-DOTA-TATE solution was reacted in 0.4 M, pH 7 ammonium acetate (NH4OAc ) under 80˚C for 1 h. However, an experiment using lutetium-177 showed that only 5 minutes in the water bath was necessary for labeling. We determined the concentration of the NH4OAc buffer solution was insignificant as long as pH was maintained above 5. We observed a maximum labeling level of 65 μCi of 161Tb per microgram of DOTA-TATE. Future work will include a stability study of the labeled DOTA-TATE and modifications to the preparation of the terbium sample in order to achieve more activity per microgram of the chelate as required by animal studies

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

Labeling and purification studies on cancer targeting DOTA-TATE labeled with radiolanthanides

Abstract only availableMolecular imaging and targeted radiotherapy are emerging fields for cancer treatment. DOTA-Tyr (3)-Thr(9)-octreotate (DOTA-TATE) is used for peptide receptor-mediated radionuclide therapy (PRMRT) in neuroendocrine tumours. These biomolecules can be radiolabeled with an appropriated radioisotope to produce radiopharmaceuticals for diagnostic and therapeutic applications. The DOTA-TATE molecule is comprised of a bifunctional chelate (DOTA) that is capable of stably binding a radiolanthanide as well as being covalently attached to a targeting biomolecule (e.g.,octreotate). Among the radiolanthanides, Ho-166, Tb-161 and Lu-177, that were used to label the peptide, Lu-177 was used to obtain optimum conditions. Direct neutron capture on Lu-176 produces Lu-177. The indirect production of Lu-177 proceeds by neutron capture on Yb-176 producing Yb-177, which beta decays to Lu-177. Chromatographic separation yields high specific activity Lu-177 that minimizes the presence of cold Lu-176. Lanthanides have similar chemical properties that allow further studies to apply similar conditions as those developed for Lu-177. In addition, longevity of half-life of Lu-177 enables longer periods of dose delivery to targeted tumors. This research focused on identifying appropriate buffer solutions and volumes that could neutralize the acidic radioisotope to appropriate pH levels to label the peptide in high yield. The sample was purified from the unlabeled peptide by using HPLC separations methods and adding stabilizing agents (ascorbic and gentisic acid) to prevent radiolysis of the radiolabeled peptide. The results for the labeled peptide with various radioisotopes shows that 0.4 M NH4OAc, 0.4 M NaOAc, and 0.01 M HEPES buffer solution in 500 µL yields 99% labeling at pH ranging from 6.0 to 7.5. The labeled ligand at equimolar ratio with the metal yields 3 mCi/µg of the ligand, whereas as high specific activity sample can label up to 6.68 mCi/µg of the ligand. Carrier free Lu-177-DOTA-TATE was labeled using 0.01 M HEPES buffer at pH 6.0 and remains stable after using ascorbic acid; gentisic acid shows interference on HPLC which may cause some purification problems. (Ho- holmium, Tb- terbium Lu- lutetium)U.S. Dept. of Energy Innovations in Nuclear Infrastructure and Education Summer MURR Undergraduate Research Scholarshi

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

Conservation and monitoring of invertebrates in terrestrial protected areas

Invertebrates constitute a substantial proportion of terrestrial and freshwater biodiversity and are critical to ecosystem function. However, their inclusion in biodiversity monitoring and conservation planning and management has lagged behind better-known, more widely appreciated taxa. Significant progress in invertebrate surveys, systematics and bioindication, both globally and locally, means that their use in biodiversity monitoring and conservation is becoming increasingly feasible. Here we outline challenges and solutions to the integration of invertebrates into biodiversity management objectives and monitoring in protected areas in South Africa. We show that such integration is relevant and possible, and assess the relative suitability of seven key taxa in this context. Finally, we outline a series of recommendations for mainstreaming invertebrates in conservation planning, surveys and monitoring in and around protected areas. Conservation implications: Invertebrates constitute a substantial and functionally significant component of terrestrial biodiversity and are valuable indicators of environmental condition. Although consideration of invertebrates has historically been neglected in conservation planning and management, substantial progress with surveys, systematics and bioindication means that it is now both feasible and advisable to incorporate them into protected area monitoring activities