R. A. Boll

Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy.

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the 225Ac daughters following α decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple α radiations and contain the decay daughters of 225Ac while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain 225Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.

Optimizations of Radiolabeling of Immunoproteins with 213Bi

Carrier-free Bi ((f1/2 = 45.6 m, an α-emitter) is available from the Ra/Ac/Bi generator system with Ra (f1/2 = 14 d) and Ac (tU2 = 10 d) being the daughters of 7340-y Th which, in turn, is the decay daughter of long-lived U. In the current generator system, Ra/Ac is adsorbed on an organic cation exchange resin (AG 50X4, X8 or highly cross-linked AG MP-50) and Bi is eluted with 0.1 Μ HI. We have found the lower cross-linked resin to be more suitable for rapid elution of Bi from the generator with Ac breakthrough of <1%. Generators were typically made from Ac separated from Ra as the breakthrough of Ra is significantly higher than that of Ac. Generator elution of Bi, labeling of MAb and HPLC purification were accomplished within 35—40 min. Radiolabeling yields of CHX-b-DTPA-conjugated MAbs (34A and 14) were >50% with specific activity of ~200 μ(Γί of Bi per 150 of conjugated protein.

Gold-Coated Lanthanide Phosphate Nanoparticles for an 225Ac in vivo Alpha Generator

Summary Retaining radioactive daughter products at a clinically relevant target site remains one of the major challenges in development of in vivo α generators with radionuclides such as 225Ac and 223Ra. In this work, we examine the ability of layered nanoparticle constructs to retain 225Ac and the first decay daughter, 221Fr. Actinium-225 is cocrystalized in a lanthanide phosphate nanoparticle consisting of varying amounts of La and Gd. Additional lanthanide phosphate layers improve retention capability while an outer layer of gold facilitates the attachment of targeting moieties for in vivo use. Retention of 225Ac in the nanoparticles is near quantitative while the 221Fr retention varies from 60-89% as a function of time, the number of layers, and nanoparticle composition. Decay corrected radiochemical yield in the multi-shell syntheses are high (76%) and comparable to or better than existing delivery approaches.

Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix

A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.

Samarium electrodeposited acetate and oxide thin films on stainless steel substrate characterized by XPS

Characterization of a samarium thin film deposited on a stainless steel substrate using electrodeposition was carried out with a Thermo Scientific K-Alpha X-ray photoelectron spectrometer. Two types of samarium electrodeposition samples were studied, one as-deposited and one heated to 700 °C in an air atmosphere. Survey scans include peaks coming from the stainless steel substrate, such as Fe and Cr. An x-ray photoelectron spectroscopy (XPS) survey spectrum, Sm 3d, C 1s, and O 1s narrow scans are shown. It was determined, using XPS, that the heating process decomposed the deposited Sm acetate to Sm2O3.

Reactor production of Thorium-229.

Limited availability of (229)Th for clinical applications of (213)Bi necessitates investigation of alternative production routes. In reactor production, (229)Th is produced from neutron transmutation of (226)Ra, (228)Ra, (227)Ac and (228)Th. Irradiations of (226)Ra, (228)Ra, and (227)Ac targets at the Oak Ridge National Laboratory High Flux Isotope Reactor result in yields of (229)Th at 26 days of 74.0±7.4MBq/g, 260±10MBq/g, and 1200±50MBq/g, respectively. Intermediate radionuclide yields and cross sections are also studied.

PURIFICATION OF THORIUM FROM URANIUM-233 PROCESS RESIDUE

ABSTRACT Thorium-229 can be used to produce 213Bi. Researchers in phase I human trials are investigating the use of antibodies labeled with 213Bi for selectively destroying leukemia cells. Other types of cancer may potentially be treated using similar approaches. Crude 229Th was liberated from Rachig rings by sonication in 7.5 M HNO3 followed by filtration. Contaminants, included significant levels of uranium, a number of other metals, and radiolytic by-products of di-(2-butyl) phosphoric acid extractant (which was used in the original separation of 233U from thorium). Thorium was selectively retained on Reillex HPQ anion-exchange resin from 7.5 M HNO3 at 65°C, where U(VI), Ac(III), Fe(III), Al(III); Ra(II), and Pb(II) were eluted. Thorium and uranium isotherms on Reillex HPQ are reported. The thorium was then easily eluted from the bed with 0.1 M HNO3. To overcome mass transfer limitations of the resin, the separation was conducted at 65°C. The resin stood up well to use over several campaigns. Other res...

Californium Recovery from Palladium Wire

The recovery of 252Cf from palladium-252Cf cermet wires was investigated to determine the feasibility of implementation into the cermet wire production operation at the Radiochemical Engineering Development Center at Oak Ridge National Laboratory. The dissolution of Pd wire in 8 M HNO3 and trace amounts of HCl was studied at both ambient and elevated temperatures. These studies showed that it took days to dissolve the wire at ambient temperature and only 2 hours at 60°C. Adjusting the ratio of the volume of solvent to the mass of the wire segment from 0.176 mL/mg down to 0.019 mL/mg resulted in little change in the kinetics of dissolution. A successful separation of 153Gd, a surrogate for 252Cf, from Pd was demonstrated using ion exchange chromatography.

Production and decay of the heaviest odd-Z nuclei in the 249Bk + 48Ca reaction

The reaction of 249Bk with 48Ca has been investigated with an aim of synthesizing and studying the decay properties of isotopes of the new element 117. The experiments were performed at five projectile energies (in two runs, in 2009-2010 and 2012) and with a total beam dose of 48Ca ions of about 9x1019 The experiments yielded data on a-decay characteristics and excitation functions of the produced nuclei that establish these to be 293117 and 294117 – the products of the 4n- and 3n-evaporation channels, respectively. In total, we have observed 20 decay chains of Z=117 nuclides. The cross sections were measured to be 1.1 pb for the 3n and 2.4 pb for the 4n-reaction channel. The new 289115 events, populated by α decay of 117, demonstrate the same decay properties as those observed for 115 produced in the 243Am(48Ca,2n) reaction thus providing cross-bombardment evidence. In addition, a single decay of 294118 was observed from the reaction with 249Cf – a result of the in-growth of 249Cf in the 249Bk target. The observed decay chain of 294118 is in good agreement with decay properties obtained in 2002-2005 in the experiments with the reaction 249Cf(48Ca,3n)294118. The energies and half-lives of the odd-Z isotopes observed in the 117 decay chains together with the results obtained for lower-Z superheavy nuclei demonstrate enhancement of nuclear stability with increasing neutron number towards the predicted new magic number N=184.