Valery Radchenko

Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes

Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% β(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 μCi).

Large scale accelerator production of 225Ac: Effective cross sections for 78–192 MeV protons incident on 232Th targets

Actinium-225 and 213Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes, as well as for some of the fission products, are presented. The cross sections for production of 225Ac range from 3.6 to 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, production of curie quantities of 225Ac is possible by irradiating a 5.0gcm-2 232Th target for 10 days in either BNL or LANL proton irradiation facilities.

Formation cross-sections and chromatographic separation of protactinium isotopes formed in proton-irradiated thorium metal

Abstract Targeted alpha therapy (TAT) is a treatment method of increasing interest to the clinical oncology community that utilizes α-emitting radionuclides conjugated to biomolecules for the selective killing of tumor cells. Proton irradiation of thorium generates a number of α-emitting radionuclides with therapeutic potential for application via TAT. In particular, the radionuclide 230Pa is formed via the 232Th(p, 3n) nuclear reaction and partially decays to 230U, an α emitter which has recently received attention as a possible therapy nuclide. In this study, we estimate production yields for 230Pa and other Pa isotopes from proton-irradiated thorium based on cross section measurements. We adopt existing methods for the chromatographic separation of protactinium isotopes from proton irradiated thorium matrices to combine and optimize them for effective fission product decontamination.

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.

Bulk production and evaluation of high specific activity 186g Re for cancer therapy using enriched 186 WO 3 targets in a proton beam

INTRODUCTION Rhenium-186g (t1/2 = 3.72 d) is a β- emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ)186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a higher specific activity, allowing it to be used more broadly for targeted radiotherapy applications. This targets the unmet clinical need for more efficient radiotherapeutics. METHODS A target consisting of highly enriched, pressed 186WO3 was irradiated with protons at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF) to evaluate 186gRe product yield and quality. LANL-IPF was operated in a dedicated nominal 40 MeV mode. Alkaline dissolution followed by anion exchange chromatography was used to isolate 186gRe from the target material. Phantom and radiolabeling studies were conducted with the produced 186gRe activity. RESULTS A 186gRe batch yield of 1.38 ± 0.09 MBq/μAh or 384.9 ± 27.3 MBq/C was obtained after 16.5 h in a 205 μA average/230μA maximum current proton beam. The chemical recovery yield was 93% and radiolabeling was achieved with efficiencies ranging from 60-80%. True specific activity of 186gRe at EOB was determined via ICP-AES and amounted to 0.788 ± 0.089 GBq/μg (0.146 ± 0.017 GBq/nmol), which is approximately seven times higher than the product obtained from neutron capture in a reactor. Phantom studies show similar imaging quality to the gold standard 99mTc. CONCLUSIONS We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity 186gRe from enriched 186WO3 targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.

Determination of distribution coefficients (Kd) of various radionuclides on UTEVA resin

Abstract Using radioisotope markers the distribution coefficients (Kd) of the following elements In, Sn, Sb, Te, Bi, Co, Fe, Nb, Sr, Ba, Ag, Cd, Zr, Hf and Ti were determined with different concentrations of HCl, H2SO4 and HNO3 for the extraction chromatographic resin Uranium and TEtraValent Actinides (UTEVA). This data can be used for separation of elements in complex mixtures, as well as for correct assessment of the elements chemistry with higher valences such as 3, 4, 5 or 6.

Separation of 44Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of 44Ti/44Sc generator system

Scandium-44g (half-life 3.97h [1]) shows promise for positron emission tomography (PET) imaging of longer biological processes than that of the current gold standard, 18F, due to its favorable decay parameters. One source of 44gSc is the long-lived parent nuclide 44Ti (half-life 60.0 a). A 44Ti/44gSc generator would have the ability to provide radionuclidically pure 44gSc on a daily basis. The production of 44Ti via the 45Sc(p,2n) reaction requires high proton beam currents and long irradiation times. Recovery and purification of no-carrier added (nca) 44Ti from scandium metal targets involves complex separation chemistry. In this study, separation systems based on solid phase extraction chromatography were investigated, including branched diglycolamide (BDGA) resin and hydroxamate based ZR resin. Results indicate that ZR resin in HCl media represents an effective 44Ti/44gSc separation system.

Proton-induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development

Scandium-44g (half-life 3.97h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175MBq (4.7mCi) batch yield of 44Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 102-103. A second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In summary, this method yields a 90-97% 44Ti recovery with an overall Ti/Sc separation factor of ≥106.

Development of 225Ac Radiopharmaceuticals: TRIUMF Perspectives and Experiences

Background: The development of radiopharmaceuticals containing 225Ac for targeted alpha therapy is an active area of academic and commercial research worldwide. Objectives: Despite promising results from recent clinical trials, 225Ac-radiopharmaceutical development still faces significant challenges that must be overcome to realize the widespread clinical use of 225Ac. Some of these challenges include the limited availability of the isotope, the challenging chemistry required to isolate 225Ac from any co-produced isotopes, and the need for stable targeting systems with high radio-labeling yields. Results: Here we provide a review of available literature pertaining to these challenges in the 225Ac-radiopharmaceutical field and also provide insight into how performed and planned efforts at TRIUMF - Canada’s particle accelerator centre - aim to address these issues

Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins

Protactinium-230 ( t1/2 = 17.4 d) is the parent isotope of 230U ( t1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R3P═S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical purity of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R3P═S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.