An electrochemical generator for the continual supply of Bi from Ac for use in targeted alpha therapy applications.

Bismuth-213 is a radionuclide of interest for targeted alpha therapy and is supplied via a radiochemical generator system through the decay of Ac. Radionuclide generators employ longer lived "parent" radionuclides to routinely supply shorter-lived "daughter" radionuclides. The traditional Ac/Bi radiochemical generator relies on an organic cation exchange resin where Ac binds to the resin and Bi is routinely eluted.

A combined inorganic-organic titanium-44/scandium-44g radiochemical generator.

Scandium-44g (t = 4.0 h) is an emerging radioisotope for positron emission tomography. It can be produced with a radiochemical generator using its long-lived parent, titanium-44 (t = 59.

Engineering a modular Ti/Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry.

Background: Sc/Sc is an attractive theranostic pair for targeted in vivo positron emission tomographic (PET) imaging and beta-particle treatment of cancer. The Ti/Sc generator allows daily onsite production of this diagnostic isotope, which may provide an attractive alternative for PET facilities that lack in-house irradiation capabilities. Early animal and patient studies have demonstrated the utility of Sc.

Production of zirconium-88 via proton irradiation of metallic yttrium and preparation of target for neutron transmission measurements at DICER.

A process for the production of tens to hundreds of GBq amounts of zirconium-88 (Zr) using proton beams on yttrium was developed. For this purpose, yttrium metal targets (≈20 g) were irradiated in a ~16 to 34 MeV proton beam at a beam current of 100-200 µA at the Los Alamos Isotope Production Facility (IPF). The Zr radionuclide was produced and separated from the yttrium targets using hydroxamate resin with an elution yield of 94(5)% (1σ).

Measurement of Ac impurity in Ac using decay energy spectroscopy.

Ac is a valuable medical radionuclide for targeted α therapy, but Ac is an undesirable byproduct of an accelerator-based synthesis method under investigation. Sufficient detector sensitivity is critical for quantifying the trace impurity of Ac, with the Ac/Ac activity ratio predicted to be approximately 0.15% by end-of-bombardment (EOB).

Developing the Ce and La pair as companion positron emission tomography diagnostic isotopes for Ac and Th radiotherapeutics.

Developing targeted α-therapies has the potential to transform how diseases are treated. In these interventions, targeting vectors are labelled with α-emitting radioisotopes that deliver destructive radiation discretely to diseased cells while simultaneously sparing the surrounding healthy tissue. Widespread implementation requires advances in non-invasive imaging technologies that rapidly assay therapeutics.

A reverse U/Th radionuclide generator for targeted alpha therapy applications.

Purpose: Thorium-226 (half-life 30.6 m) is a radionuclide of interest for use in targeted alpha therapy applications. Due to its short half-life, Th must be provided through a radionuclide generator system from its parent U (20.

Thorium chelators for targeted alpha therapy: Rapid chelation of thorium-226.

One of the main challenges in targeted alpha therapy is assuring delivery of the α-particle dose to the targeted cells. Thus, it is critical to identify ligands for α-emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium-227 (t = 18.

Extraction chromatography of Ac and lanthanides on N,N-dioctyldiglycolamic acid /1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide solvent impregnated resin.

The alpha-emitter Ac (t = 9.92 d) is currently under development for targeted alpha-particle therapy of cancer, and accelerator production of Ac via proton irradiation of thorium targets requires robust separations of Ac from chemically similar fission product lanthanides. Additionally, the lanthanide elements represent critical components in modern technologies, and radiolanthanides such as Nd (t = 3.

Guest Edited Collection: Radioisotopes and radiochemistry in health science.

Radioisotopes can be produced artificially from stable nuclei through the interaction with particles or highly energetic photons. In combination with modern detection and counting techniques, radioisotopes and radiochemical methods uniquely contribute to the health sciences. This Collection showcases salient aspects of medical radioisotope science ranging from the production, recovery and purification of radioisotopes to the methods used to attach them to biomolecules.

Production of Pa by proton irradiation of Th at the LANL isotope production facility: Precursor of U for targeted alpha therapy.

Uranium-230 (t = 20.8 d) is an alpha-emitting radionuclide that has potential application in targeted alpha therapy (TAT) of cancer. Its parent isotope Pa (t = 17.

Large-Scale Production of Te and Sb for Radiopharmaceutical Applications.

Radionuclides find widespread use in medical technologies for treating and diagnosing disease. Among successful and emerging radiotherapeutics, Sb has unique potential in targeted therapeutic applications for low-energy electron-emitting isotopes. Unfortunately, developing Sb-based drugs has been slow in comparison to other radionuclides, primarily due to limited accessibility.

Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins.

Protactinium-230 ( t = 17.4 d) is the parent isotope of U ( t = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT).

Synthesis and radiometric evaluation of diglycolamide functionalized mesoporous silica for the chromatographic separation of actinides Th, Pa and U.

The separation of Th, Pa, and U is of high importance in many applications including nuclear power, nuclear waste, environmental and geochemistry, nuclear forensics and nuclear medicine. Diglycolamide (DGA)-based resins have shown the ability to separate many elements, however, these resins consist of non-covalent impregnation of the DGA molecules on the resin backbone resulting in co-elution of the extraction molecule during separation cycles, therefore limiting their long-term and repeated use. Covalently binding the DGA molecules onto silica is one way to overcome this issue.

Alpha-Emitters and Targeted Alpha Therapy in Oncology: from Basic Science to Clinical Investigations.

Alpha-emitters are radionuclides that decay through the emission of high linear energy transfer α-particles and possess favorable pharmacologic profiles for cancer treatment. When coupled with monoclonal antibodies, peptides, small molecules, or nanoparticles, the excellent cytotoxic capability of α-particle emissions has generated a strong interest in exploring targeted α-therapy in the pre-clinical setting and more recently in clinical trials in oncology. Multiple obstacles have been overcome by researchers and clinicians to accelerate the development of targeted α-therapies, especially with the recent improvement in isotope production and purification, but also with the development of innovative strategies for optimized targeting.

Separation of 103Ru from a proton irradiated thorium matrix: A potential source of Auger therapy radionuclide 103mRh.

Ruthenium-103 is the parent isotope of 103mRh (t1/2 56.1 min), an isotope of interest for Auger electron therapy. During the proton irradiation of thorium targets, large amounts of 103Ru are generated through proton induced fission.

Chromatographic separation of the theranostic radionuclide Ag from a proton irradiated thorium matrix.

Column chromatographic methods have been developed to separate no-carrier-added Ag from proton irradiated thorium targets and associated fission products as an ancillary process to an existing Ac separation design. Herein we report the separation of Ag both prior and subsequent to Ac recovery using CL resin, a solvent impregnated resin (SIR) that carries an organic solution of alkyl phosphine sulfides (RP = S) and alkyl phosphine oxides (RP = O). The recovery yield of Ag was 93 ± 9% with a radiochemical purity of 99.

Radiometric evaluation of diglycolamide resins for the chromatographic separation of actinium from fission product lanthanides.

Actinium-225 is a potential Targeted Alpha Therapy (TAT) isotope. It can be generated with high energy (≥ 100MeV) proton irradiation of thorium targets. The main challenge in the chemical recovery of Ac lies in the separation from thorium and many fission by-products most importantly radiolanthanides.

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

A new method has been developed for the isolation of Ra, in high yield and purity, from a proton irradiated Th 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.

Proton-induced production and radiochemical isolation of Ti from scandium metal targets for Ti/Sc 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 Sc is the Ti/Sc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility.

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

Introduction: Rhenium-186g (t = 3.72 d) is a β emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction Re(n,γ)Re, which results in low specific activities limiting its use for cancer therapy.

Separation of Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of Ti/Sc 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, F, due to its favorable decay parameters. One source of Sc is the long-lived parent nuclide Ti (half-life 60.

Large scale accelerator production of Ac: Effective cross sections for 78-192MeV protons incident on Th targets.

Actinium-225 and Bi 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 Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of Ac.

Monooxorhenium(V) complexes with 222-NS MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation.

Introduction: Targeted radiotherapy using the bifunctional chelate approach with Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications.

Methods: A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222-MAMA(N-6-Ahx-BBN(7-14)NH) were synthesized, complexed with rhenium, radiolabeled with Tc and Re (carrier added and no carrier added), and evaluated in initial biological distribution studies.